Genetic Testing Guide

With the generous support of the Collins Medical Trust this interactive guide is designed to stimulate discussion and elicit consumer values on genetic testing. Genetic testing is an important and powerful technology that is impacting health care planning and decision making. To track and better understand this rapidly evolving technology, Geneforum has put together this guide. This guide is integrated with the Genetizen – a blog authored by experts in the field of bioethics, genetics, and healthcare who comment on and analyze current developments in the field.

Breast cancer genetic counseling helping women in England

The United Press International reported yesterday: More women are seeking out genetic services to learn about family breast-cancer risk, and a Welch review found many have less stress and worry. "Many people have spent years worrying about cancer in their family," said review co-author Rachel Iredale of the Institute of Medical Genetics at Cardiff University.

A genetic risk assessment enables people to reach a better understanding of hereditary breast cancer, their own personal risk, and means access to additional services, such as extra mammography screening or genetic testing, is often easier. Most people are satisfied with the service they receive.

The press release concludes by citing the source of the information: three studies of 1,251 women who underwent genetic risk assessment for hereditary breast cancer. All of the studies showed that genetic counseling improved patients' psychological well-being and decreased their levels of anxiety and worry about developing cancer, according to the review in The Cochrane Library.

I've been reading about this study in several other sources and will track it down to see what else the study itself can add. More in another blog entry.

Marie Godfrey, PhD

Can a genetic test predict your chances of heart disease?

Internet news stories are boring for a while and then two interesting things can come along the same day. Today, just as I finished completing a survey on nutrigenomic genetic testing--the testing that claims to tell you how to change what you eat and how you treat your body, based on your genetic makeup--I found a slew of stories stating that there is no genetic link for heart disease risk.

The stories are in many places, but most of them read the same, starting as follows:

 No genetic link found for heart risk, study says

Tests failed to find mutations that would predict cardiovascular disease

Updated: 12:13 p.m. PT April 11, 2007
CHICAGO - Genetic testing failed to find any gene mutations that predict a higher risk of heart disease, a study released on Tuesday said.

Scientists at Yale University worked up the genetic profiles of nearly 1,500 people to examine 85 genes that smaller, earlier studies suggested might confer susceptibility to heart problems.

More than half the patients had come to a hospital having suffered a heart attack or other acute symptoms, while the others had experienced no heart trouble.

Only one genetic variation showed even a modest association to heart problems in the study, which was published in the Journal of the American Medical Association.

“We therefore conclude that our findings, in this large sample ... cannot support that this panel of gene variants contains bona fide (heart disease) risk factors,” study author Dr. Thomas Morgan wrote. Morgan is now at Washington University in St. Louis.

So, can nutrigenomics genetic testing--or any other form of genetic testing--predict your risk of getting heart disease? Not according to the Yale study. BUT, as I noted in an earlier blog entry, there are some forms of heart conditions that have been shown to have strong genetic components to them. One of these is the type of cardiomyopathy that is all-too-often the cause of sudden death of people in their 20s and 30s. For a story related to this, please select the Your Stories tab at the top of the page and read about the woman who cheated death.

Marie Godfrey, PhD

Catching problems before they destroy lives

And here’s the latest news: Oregon wins by a score of 49 to Utah’s 46!! Football? A very defensive basketball game? Certainly not soccer, hockey, or baseball. So, what’s the game?

The game is Life and the scores are based on available newborn screening for life-threatening conditions and diseases. If you happen to live in Washington State, the score would be 14. If your child is affected by one of the genetic conditions not screened for in Washington—or Virginia, where Stephen Monaco was born—there’s a very small, but real, possibility that your child could die or be severely disabled by an undiagnosed genetic condition.

Here’s what happened to Stephen:

"Stephen came into the world just like any other healthy baby," Jana Monaco, Stephen's mother, says. But when he was three-and-a-half, he had a stomach virus when his parents put him to bed one night. "That was the last time we said goodnight to each other and ... I love you," Jana says.

When he woke up, he had suffered a metabolic crisis that nearly killed him. "They told us then, 'If he makes it through the weekend, he won't be the same child you knew and loved,'" Jana says. Just 24 hours later, he was left a severely disabled child with complicated medical issues. "It was one day. He went from making his grandmother's birthday cake to being on life support," Tom Monaco, Stephen's father, says.

Stephen was found to have isovaleric acidemia (IVA), a genetic metabolic disorder not then screened for in his birth state (Virginia). The Monacos encouraged Virginia to screen for the 29 conditions recommended by the American College of Medical Genetics. "The first six months after the expanded screening, 22 babies were picked up with these disorders," Jana says. Among those screened, Stephen’s sister, Caroline, was also found to have IVA. She was placed on a restrictive diet and is happy and healthy at 4 years.

Stephen can't walk, talk or feed himself. But he inspires his parents and many others everyday. "If we can help one family not have to go through this, then we've done our job," says Tom. That's how Stephen is making a difference.

You can read the full story and view a video from the Ivanhoe Newswire and can find out what your state screens for by checking the frequently updated listings.

By the way, although the subject for this blog entry is identified as "genetic testing", newborn screening does not look at DNA, but at the effects of specific genes on chemicals in the blood. Some hospitals do now save the blood samples taken from the heel of a newborn just after birth and severl weeks later as sources for additional testing and for potential genetic testing using DNA extracted from the sample.

Marie Godfrey, PhD

Cheap genome maps--under $1000?

The big hype this week in genetic testing comes from the addition of yet another company to those hoping that we are so interested in learning about ourselves that we will fork over $1000 (or $999 or $985 at a discount) for a map of our own genome.

Here are some things about this subject you might want to know:

1. How do you take a sample? You won't know the details until your kit arrives, but you will most likely learn that the sample will be saliva or a rubbing from the inside of your cheek. You don't have to provide a blood sample. If the company info doesn't provide clear enough instructions, be sure you rinse your mouth well before taking a sample; you'd probably hate to pay $1000 for the genome of that beef or corn you just ate.

2. What are you consenting to when you provide a sample? In one case, you have to give your name and an address (e-mail?) before you get to read this part. I chose not to give my name, so I couldn't see the consent form. The other company's pages took a while to load (maybe it's my machine), and I found them quite lengthy when they did arrive.

To get the sample kit, you have to give a mailing address; one company requires you to certify that you actually live in the state to which the sample kit is being sent.

3. Will your information be protected? Because I couldn't see the consent form on one site, I would have to rely at the moment on a news release advertising one genome company. It states that the "founders say the personal data in their system is secure and under the user's control, protected by more than a dozen levels of authentication and encryption from the lab to the user" However, the article also likens the result posting to "a kind of genetics-focused MySpace or Facebook". In my mind, these sites are for sharing information with others, so there's some confusion in my mind about whether the company expects people to want to protect their privacy or to share their results. The website promotes adding other people's samples to the order as well as selling family members on the idea.

The other site I checked has a full service agreement and consent. If you're used to just checking "I accept" on these, you may want to check out what you're agreeing to before you do. Lots of legal stuff.

3. What will the results look like? Your genome map will not look like James Watson's or Craig Venter's. The map is based on SNPs, not full DNA sequencing. Here's what one company does:

Your DNA is washed over a small microchip-like device that contains short strands of synthetic DNA. The synthetic DNA fragments latch onto the pieces of your DNA that are a complementary match. Then a laser-scanning step reveals which strands of synthetic DNA are stuck to your DNA to determine your genotype. The chip used in our process . . . reads more than 550,000 SNPs (single nucleotide polymorphisms).

A SNP is a single nucleotide variation, such as a guanine instead of a cytosine. Your "map" will be only a fraction of the 10 million SNPs that are estimated to be in the human genome.

Oh, and by the way, you can see your results only online and the company always has access to your information. Otherwise, how could they provide "updates" based on your data? Check out the computer requirements for viewing the data. I didn't know that Adobe Acrobat Reader 9 was out yet and I know that "player" programs have to be frequently updated.

4. What do I really learn? Be prepared for a disappointment. Although you will receive results for "nearly 600,00 datapoints", you still may not know much about your present or future. One company focuses on 14 "known" conditions, including dry vs. wet earwax, and the other company features 17 conditions. Is that what you expected?

And, finally, what I always say about genetic testing. Before you order a genetic test, figure out what you are going to do with the results. Then, spend your $1000 if you must. It's not my children's heritage.

Marie Godfrey, PhD

 

Genetic Design

There's an interesting article in this month's Portfolio.com. While primarily about 23andMe and the future of "Web-surfing your own DNA," the thing that caught my eye was the interactive feature.

This graphic was created for the story by Martin Krzywinski, who placed the human genome in a circular pattern. The chromosomes are represented on the outside of the circle and colored dots are for disease-related genes. The lines inside the circle show gene linkages and similarities. Based on a quick glance of Krzywinski's site, it looks like the feature was created using Circos, "a Perl application for the generation of publication-quality, circularly composited renditions of genomic data and related annotations."

Genetic information is inherently complex to understand, represent, and convey to non-scientists. Images can be incredibly powerful tools of communication, as people respond to images instinctively based on their personalities, associations, and previous experience.

More and more people are taking part in genetic tests, services, and research. It will be fascinating to see how advances in graphic design either enable or undermine our ability to fully comprehend and interact with all the resulting genetic information.

What good/bad examples of genetic design have you seen?

Genetic testing discussed by NPR

The National Public Radio site has an article posted online by Sarah Handel. The story includes also a link to audio of the broadcast. The story starts:

Our bodies are full of untold secrets about our futures. Turns out, predispositions for various diseases are plain as the nose on your face... If only someone takes a look at your DNA. OK, that's simplifying things, but there are now a variety of tests you can take to see if, say, a family history of breast cancer means you'll get it too. Or if you're going to pass cystic fibrosis on to your kids. Have you gotten tested? Do you want to? How much do you want to know about your medical future? What if one day, there's a test that will tell you how long you'll live (barring accidental death, of course)? Would you want to know? Is there a difference between knowing for yourself, and knowing about what genetic markers you could saddle your kids with?

You may find the stories and comments attached to the article very interesting and informative. For example,

How do you suggest stopping insurance companies from not insuring a person or dropping them if they're tested? They regularly drop people for pre-existing conditions. If you aren't tested, you at least have plausible deniablity. I just don't think it's worth the chance. Tested when you're born for Alzheimers by your parents and denied insurance at 21? Or have your entire family insurance cancelled while you're still a baby because you test positive? This is happening now - it's not a "what if". I would track family members with conditions within the family.

Check it out if you're interested in genetic testing and its implications.

Marie Godfrey, PhD

 

Genetic testing for breast cancer: marketing through fear

I wondered the other day when I saw a commercial advertising genetic testing for "breast cancer genes" whether the company that patented the tests for BRCA1 and BRCA2 and controls this segment of the genetic testing market was starting to have declining sales. They haven't advertised before; why now?

Perhaps their advertising is justified by the fact that, according to an article in the New York Times, "only 30,000 of more than 250,000 American women estimated to carry a mutation in BRCA1 or a related gene, BRCA2, have so far been tested."

In any case, the advertisement caught my attention and that of a number of other people--including the Attorney General of Connecticut. According to an article from the phg Foundation,

A US television advertisement for familial breast cancer testing has attracted criticism from oncologists and geneticists, who say that advertising a specialised genetic test to the general population could cause anxiety among women for whom the test is not actually appropriate. Director of cancer genetic counselling at the Yale Cancer Center Ellen T. Matloff said: “It really preys on the fears of our society, and one of those fears is getting breast cancer” (see New York Times article). Inherited mutations in the BRCA1 or BRCA2 genes can confer a lifetime breast cancer risk of up to 85%, and an ovarian cancer risk of up to around 40%; however, only a small proportion of breast cancer cases in a population arise in women with a BRCA mutation. Normally, only women considered to have an increased risk of carrying a mutation based on their family history (such as several affected relatives, and/or early onset cases in relatives) are referred for genetic counselling and the option of genetic testing.

The attorney general of US state Connecticut has ordered an investigation of the claims made by Myriad in the advertisement. However, Myriad president Gregory Critchfield has said: “The purpose of the BRACAnalysis public awareness campaign is to save lives" by identifying BRCA mutation carriers (see press release). He added that: "We are committed to working with healthcare providers around the country to provide useful resources for them to offer hereditary risk assessment, counseling and genetic testing to their patients". However, the key issue is what proportion of the women prompted to ask about genetic testing will be at genuinely increased risk of having a mutation, and whether direct advertising of this genetic test is appropriate.

The ad I saw did not seem to fit with Myriad's contention that the "campaign is being initiated with the hope that women with a family history of breast or ovarian cancer will contact their physicians to learn more about their risk of developing cancer and the actions they can take to reduce their risk." (see press release) I also find it interesting that I am in Portland, OR, but, according to the press release, the "advertising component is being conducted specifically in four areas, namely Boston, Hartford, Providence and New York City." Perhaps The DISH network enabled me to see something being broadcast elsewhere.

According to the New York Times:

Critics say that advertising such a complex screening test to the general population might create unnecessary anxiety among women and lead to overuse of the test, which costs $3,120.

“It really preys on the fears of our society, and one of those fears is getting breast cancer,” said Ellen T. Matloff, director of cancer genetic counseling at the Yale Cancer Center.

The Connecticut attorney general, Richard Blumenthal, said his office had issued a subpoena for information from the company. “We’ve determined that there’s enough serious and significant doubt about the accuracy of some of their claims that we feel a strong need to investigate,” he said in an interview.

Myriad officials are reported as responding:

Myriad, which said it would cooperate with Mr. Blumenthal’s request, defends the commercial and other elements of what it calls a public awareness campaign. The company says that while its test has been given to about 200,000 women since 1996, only 3 percent of the women believed to harbor the harmful mutations that can be detected by the test have been identified so far. Therefore, the company says, there is a need for much more extensive testing.

“What we are doing is raising public awareness so they will have a conversation with their health care providers,” said Dr. Gregory C. Critchfield, president of Myriad’s genetic testing business. “Those individuals, if they are tested and identified, can avail themselves of means to reduce the risk of cancer.”

The New York Times summarizes details of the test as follows:

Myriad’s test, called BRACAnalysis, detects mutations in genes called BRCA1 and BRCA2. Women with a clinically significant mutation in one of those genes have a 35 to 84 percent probability of developing breast cancer by age 70 and a 10 to 50 percent probability of developing ovarian cancer, far higher than for women in general.

Women with the mutations can reduce their risk of cancer by taking certain cancer-prevention drugs or having their breasts or ovaries removed. They can also be screened more frequently for early detection.

But mutations in the genes account for less than 10 percent of all cases of breast cancer. And only 1 in about 400 women has the mutation. (The risk of a mutation is about 10 times as high for women who are Ashkenazi Jews, but they can be tested for three specific mutations, for a cost of $460.)

In an interesting side note, the article claims that only docotrs can order the test. I don't remember that being a requirement when I last checked their website. And, women getting genetic tests from other online sources are, in fact, getting the Myriad test.

Many of the 200,000 women who have had the test since 1996 may have been influenced by Myraids' early marketing (with the same ad) in a five-month test in Denver and Atlanta in late 2002 and early 2003. That campaign, and scientific articles on BRCA1 and 2 have been enough to generate enough business to last over 5 years. According to the New York Times,

Dr. Critchfield said Myriad waited nearly five years to start the new campaign to give more time for health care providers to learn to handle genetic testing. "We are in a far different place today than we were then," he said.

Well, at least one thing is probably true: I doubt Myriad will call me again for help in writing documents. By the way, those of you who remember that I do not generally name specific companies should know that Myriad is the sole provider of the BRCA1 and 2 tests; and the ads don't make this very obvious. So, I have referred to them by name.

Marie Godfrey, PhD

Genetic testing sheds light on degenerative eye disesase

Now, here's a genetic test I would be very interested in and would be willing to pay for. My mother and her sister both have lost much of their eyesight to macular degeneration. I thought there was just "wet" and "dry" macular degneration and, frankly, have been avoiding the issue because I greatly fear blindness.

I learned today in an article in Science Daily (http://www.sciencedaily.com/releases/2007/02/070213173952.htm) that at least four genes identified for varieties of macular degeneration and genetic tests already exist. Also, treatments are being approved now that might be helpful to me. I already have my eye exams yearly, including a retinal examination. And I know that treatments are being tested and approved. Now, it may be time for me to decide whether to have genetic testing and, if so, where to have it done.

I've told you readers many times to look at how you will deal with the results before you choose to have genetic testing, and the authors of today's article in Science Daily--whose title I stole for the title of this blog entry--apparently seem to agree. I'm writing today about that article, rather than the University of Michigan Health System news release, or the original article in the Archives of Ophthalmology because I feel that the public is more likely to see common newspapers or online sources than professional journals or university notices.

The article quotes Dr Radha Ayyagari as urging people to prepare for all possible results:

Genetic counseling is a crucial part of the genetic testing process, particularly when the patient may face the possibility of blindness, says Ayyagari. The family needs to prepare for all possible test results, understand the implications of test results for the patient and other family members, and be aware of the limitations of genetic testing. If physicians do not have the time or skills to provide this background, Ayyagari urges them to refer their patients to genetic counselors.

So, here's some of the news I read in the article:

Ayyagari and her colleagues report on 350 genetic tests conducted since 1999, when the U-M Ophthalmic Molecular Diagnostic Laboratory became one of the first laboratories in the nation to receive government approval for ophthalmic testing under the Clinical Laboratory Improvement Amendment (CLIA). For each test described in the current study, scientists analyzed one or more of eight genes known to cause diseases of the retina.

Here's the response to one of my first criteria for submitting to genetic testing: the laboratory doing the test has to be CLIA certified. Although there is no specific certification yet for genetic diseases, a laboratory meeting CLIA standards for biologic testing is more likely to be qualified to perform the tests in which I would be interested than a laboratory not CLIA certified.

Costs and how to get the test done?

The U-M Kellogg Eye Center's Ophthalmic Molecular Diagnostic Laboratory was established by Paul A. Sieving, M.D., Ph.D., formerly a U-M faculty member and now director of the National Eye Institute. For further information on the laboratory, see the web site at http://www.kellogg.umich.edu/research/eyegenetest.

I checked the site and found the contact information I needed.

What do the tests test? The necessary info is available on the website. Plus, there's a lot of information directed to the interested person:

Please let us know if you are interested in a gene that is not on this list.

Indications for molecular diagnostic testing

  • Clinical diagnosis for patients with signs and symptoms of disease.
  • Pre-symptomatic testing for individuals who do not have the disease but, given family history, are at risk for the disease.
  • Carrier testing for individuals who may carry a gene mutation that can be passed on to children.

Comprehensive services include:

  • Certified laboratory testing (CLIA ID# 23D0964501)
  • Written report of results for the patient
  • On-site genetic counseling for patients both before and after testing. The pre-test session educates patients about the scope of testing and helps them set realistic expectations; the post-test session will help patients interpret results and their implications for the patient and family members.

The Ophthalmic Molecular Diagnostic laboratory accepts referrals from:

  • Ophthalmologists, genetic counselors, geneticists and other health care professionals
  • Patients with a designated health care provider to receive the report and discuss the results with them

For additional information, contact
phone 734-647-6347
fax 734-936-7231
eyegenetest@med.umich.edu

How good are the tests? I can check the peer-reviewed professional publication, the credibility of the journal in which the article was published, and previous publications and determine for myself whether the news article is accurate in saying:

Ayyagari and her colleagues report on 350 genetic tests conducted since 1999. For each test described in the current study, scientists analyzed one or more of eight genes known to cause diseases of the retina.

Of the 350 tests, 266 were performed to confirm a clinician's diagnosis, by far the most common use of genetic testing for eye disease. Another 75 tests sought to determine whether an individual was a "carrier" of a disease, and nine tests were used to predict the likelihood that an individual with a family history of a given eye disease would go on to develop it.

Ayyagari's team was able to determine the molecular basis of the disease in half of 266 tests conducted to confirm a diagnosis. The study also reported that a diagnosis could not be confirmed in 133 cases, or half the tests conducted to confirm a diagnosis.

And, I can read what the scientists say about the purpose of the testing and how the testing is used:

The authors observe that genetic testing for eye disease is a relatively new and evolving practice. Says Ayyagari, "Molecular diagnostics does not replace the necessary expertise of the ophthalmologist; rather, it adds a new tool to the ophthalmologist's diagnostic arsenal."

These results are significant because many retinal diseases present similar symptoms, and it is sometimes difficult for even the most skilled specialist to distinguish one from the other. By comparing a patient's DNA to known disease-causing genes, scientists deliver information needed to confirm or rule out a diagnosis. To date, scientists have identified over 130 genes associated with retinal disease, such as retinitis pigmentosa and macular degeneration.

What about all those negatives?

"It is very difficult for patients to understand that the test may not be definitive," says Ayyagari. "Genetic testing may not always yield the firm facts we receive in other kinds of testing, such as blood tests for cholesterol levels."

I have a lot of what I need from the Science Daily article, which I consider a reputable source of information, and can access a lot more with some more time at the computer and in the library.

Now, all I have to deal with is what I started with: what will I do with the results? I will not do the testing until I can answer that question.

If you have had genetic testing, what steps did you go through deciding what to do? Perhaps you ordered a test for the fun of it, were encouraged by a friend, or wanted to learn something without your insurance company knowing. Go to the "Your Stories" link at the top of the page, and send us your story. You will have to supply your name and e-mail addres, but neither will be printed or shared with organizations beyond Geneforum.

Marie Godfrey, PhD

 


 

 

 

 

 

 

 

Genetics tests available to healthy young adults

have you ever considered having a gentic test done? How would you get the information you need? How would you deal with the results?

These are some of the questions adults 25 to 40 years old may be asking.

A new initiative from the National Cancer Institute has been launched to "investigate the interest level of healthy, young adults in receiving genetic testing for eight common conditions."

Called the Multiplex Initiative, the study will also look at how people who decide to take the tests will interpret and use the results in making their own health care decisions in the future.

The test being used is designed to yield information about 15 different genes that play roles in type 2 diabetes, coronary heart disease, high blood cholesterol, high blood pressure, osteoporosis, lung cancer, colorectal cancer, and malignant melanoma.

"The Multiplex Initiative will provide insights that will be key to advancing the concept of personalized medicine," said NHGRI Scientific Director Eric Green, M.D., Ph.D. "As genomic technologies are introduced for wider use, researchers and clinicians will need to know how genetic susceptibility tests will be received by patients. This study will be an important first step in understanding how such testing can be practically used in primary care settings."
According to the news release,
Researchers at Henry Ford Health System, a major health provider in metropolitan Detroit, are recruiting individuals between the ages of 25 and 40 to volunteer to participate in the study. The participants are being selected through patient lists from Health Alliance Plan, the largest managed care plan in Michigan, owned by Henry Ford Health System and the Henry Ford Medical Group, the health system's group medical practice of more than 900 physicians and scientists. A total of 1,000 participants who meet the study's eligibility requirements will be offered free multiplex genetic testing. A total of 1,000 participants who meet the study's eligibility requirements will be offered free multiplex genetic testing.
I do not know whether they will accept volunteers not in the Health Alliance Plan or the Henry Ford Medical Group, but it's worth contacting them if you are interested.
Waht about security of your genetic information? It appears that the group understands that young adults are very concerned about this issue.
To protect patient privacy, test results obtained during the Multiplex study will not automatically become a part of participants' medical records. However, participants who want to share their test results with their health care providers may do so.
The actual genetic tests will be conducted at the Center for Inherited Disease Research (CIDR), a world-class genotyping facility that is jointly operated by NIH and The Johns Hopkins University.
Wow, I'm impressed. It's not often a news release knows enough about Hopkins to call by its correct name The Johns Hopkins University. Not only is the "s" on Hopkins, the word "The" is in its proper place. Cheers to my alma mater.
Marie Godfrey, PhD


Heads they win; tails you lose--genetic testing and insurance

While the U.S. legislature debates whether discrimination is occurring in insurability of its citizens, many Canadians are paying higher premiums for critical care insurance even when genetic tests are negative. This report comes from cbc news.

Canada has public health care for ordinary illnesses, with more limited protection for debilitating conditions such as cancer. People can buy additional insurance to cover these potential problems, and insurance in this category is a fast-selling product. It covers such things as strokes, heart attacks and some types of cancer or diabetes.

Susan Goldberg of Thunder Bay, Ont. didn't inherit the genetic mutation that led to the deaths of her mother and grandmother from cancer; but she still pays 75 per cent more for her insurance than the typical client. A test showed that [she] didn't inherit the genetic mutation that led to the deaths of her mother and grandmother from cancer.

Why wasn't her negative test result taken into account in determining the insurance premium? It turns out that insurers

. . . sometimes set rates for a client based on their family history, even when genetic tests show that the individual doesn't have the genetic mutation that has made their families high-risk in the past.

That is, insurance companies rely more heavily on family history than genetics.

So in assessing someone looking for insurance for breast cancer, the company would consider such things as:

  • Whether her breasts were exposed to radiation.
  • Whether she had her first child after the age of 30.
  • Whether she had prolonged hormone replacement therapy after menopause.
  • Whether she had a positive genetic test.

A check mark beside any one of those things is likely to increase the premium. But there's no box to check in the absence of any one of those conditions, and nothing saying how negative genetic test results would affect a rating.

Although insurance companies--by law--cannot require someone to have a genetic test, they can use the results if the person has had such a test. In fact, not revealing the results of such a test can be considered insurance fraud.

Oh, you say, that's Canada, not the U.S. Have you any idea how U.S. insurance companies decide to charge higher premiums or deny insurance? Probably not.

Is there discrimination based on genetic makeup? Yes, I believe there is.

Marie Godfrey, PhD

New information on the genetics of Type 2 diabetes

Although I've chosen "genetic testing" as the topic for this blog entry, none of the new "genes" reported in the latest news have had genetic tests developed for them yet. So, you cannot run out and get tested for these genes yet.

Today, Associated Press medical writer Lauran Neergaard wrote an article, New diabetes risk factors found, that is hitting all the newspapers and online services. The author writes:

Scientists have found clusters of new gene variants that raise the risk of Type 2 diabetes — and how the researchers did it is as important as what they found.

So, what did they find and what is the technique that is so important?

First, their findings:

Four previously unknown gene variants that can increase people's risk of Type 2 diabetes, and confirmation that six other genes play a role, too. The highest-risk variants can increase by 20 percent someone's odds of developing Type 2 diabetes. Among the genes implicated:

  • One that helps pump zinc into insulin-producing pancreatic cells, raising questions about the metal's role in insulin secretion.
  • A pair previously linked only to certain cancers, another brand new area for diabetes researchers to probe.
  • A region of chromosome 11 where genes of any sort had never been described.

Second, how did they do it?

The new work scanned DNA to find patterns of small gene variations known as SNPs (pronounced "snips") more common in diabetics. SNPs can serve as signposts for tracing disease-promoting genes. To be certain the implicated SNPs were involved, the researchers then checked for them in still more volunteers, ultimately testing DNA from 32,500 people in Britain, Finland, Poland, Sweden and the U.S.

This type of research — called a "genome-wide association" study — promises to usher in a new era of genetics. Most breakthroughs so far have come from finding a mutation in a single gene that causes illness. But some of the world's most common killers, such as heart disease and diabetes, are caused by complex interactions among numerous genes and modern lifestyles — and teasing out the genetic culprits until now has been almost impossible.

You do not need to know what SNPs are to understand the research, but you might want to know about a word not used in the article--genomics. Genomics is the study of an organism's entire set of genetic material. Genomic studies are typically conducted with samples from more than one person, mouse, virus, etc., although it is possible to map the genome of a single individual. In this search for DNA variations possibly associated with Type 2 diabetes, 32,500 different sets of DNA were involved.

One other bit of information that might be helpful to you. Type 2 diabetes is the variety of diabetes initially thought to result strictly from obesity and lack of exercise. People generally develop this type as adults. Type 1 diabetes, also known as juvenile diabetes, typically develops much earlier. We've known for some time that genetics plays a factor in the potential for developing Type 2 diabetes. Now we know that at least 10 genes may be involved. Therefore, there is no single "gene" for diabetes; there are many that may play a part.

You can access the full AP article, but the Science and Nature articles both require subscriptions.

Marie Godfrey, PhD

New multi-gene test for predicting breast cancer probability

The United Press International posted a news article today stating that a U.S. biotech firm has launched "the first genetic-based, breast-cancer-risk test to the global market.

According to the news release,

The test, to be sold as OncoVue, uses a patient's personal history and gene-based information to determine future breast-cancer risk.

"OncoVue has undergone over seven years of research, and the genetic information for this test came from the testing of over 8,000 women with and without breast cancer from five geographic regions of the United States, giving us the support to introduce the test to an international market." said Craig Shimasaki, InterGenetics' chief executive officer and president.
InterGenetics said U.K. genetic clinic chain Opaldia will release OncoVue in the United Kingdom and Ireland under an exclusive agreement.
The test, which could be a rival for Myriad Genetics test for BRCA1 and BRCA2 genes, involves a medical history questionnaire, followed by use of a mouthwash, which collects cheek cells form the patient for DNA analysis. The OncoVue test analyzes combinations of genes, rather than any single gene alone.

The cancer risk supposedly detected by the test is for "sporadic breast cancer" which, according to the news release, accounts for 90 percent to 95 percent of all breast cancer cases. Myriad's test, on the other hand, examines the genes believed to be responsible for about 5% of all breast cancers.

Let's be cautious until we learn more about the test. Remember that genetic tests do not need FDA approval so this possible layer of quality control is not in place. I, for one, will need to learn more about the basis for the test and its success rate.

Marie Godfrey, PhD

Personalized medicine is possible, but is it likely?

I found an interesting article in the Feb. 27th issue of the Arizona Republic that suggests that genetic testing used for adpating treatment to an individual person is still a ways off and--perhaps--may only be another way of separating those with money from those without. The author, Ken Alltucker, starts as follows:

Genes can be powerful predictors of a person's future health problems, but testing a patient's genes to tailor treatment strategies remains at the cutting edge of health care and legal professions.

The promise behind personalized medicine is that genetic tests can be used to craft ways to detect, treat or delay disease. Yet using genetic tests to tailor health care strategies is rarely done. These tests are too expensive for the typical patient, and many doctors aren't trained properly to administer, assess or use the tests for patient care.

He then discusses the obstacles to personalized medicine:

Many things need to happen before personalized medicine becomes routine care, though. Not all doctors are convinced that DNA triggers a disease as much as environmental or lifestyle factors. Ethical concerns persist about how data from genetic tests will be used.

Perhaps the biggest hurdle is the expense to administer the tests and whether insurers will pick up some costs as part of standard care.

Another major hurdle before such tests become part of standard patient care is ensuring that patients can easily afford them.

The costs of genetic testing have come down dramatically because of lower costs of equipment and computers. Still, these tests can cost $3,000 or more, for example, to detect whether a breast cancer patient is likely to experience a recurrence.

He finishes by noting that some "lawyers and health care interests worry that personalized medicine will create a caste system of sorts" and wondering, "are we going to create a society with two tiers of patients? Those who can afford these tests and those who cannot?"

So, besides the promises that individualized medicine can provide better health care, what's fueling the media hype that genetic testing is the wave of the future? Think . . . lawsuits.

More on this in the next blog entry.

Marie Godfrey, PhD

What will prostate genetic testing do for men?

I've written several times about women who have double mastectomies after learning that they carry a BRCA1 or BRCA2 mutation and, as a result, are many times more likely to develop breast cancer than women without one or both mutations.

The news in the past couple of days has been describing 5 genes identified as conferring risk of prostate cancer. Apparently the effects are additive in that one gene mutation alone is not enough to give increased risk.

None of the articles I have read indicates what men will do with the information if a test is developed and they learn of their increased potential for getting prostate cancer. Apparently the genes do not affect PSA (prostate specific antigen) levels, so there's no indication that the current standard test for prostate cancer would be helpful.

Naturally, screening of all types could be done more frequently, as could mammograms for women. But, I can't help but wonder whether at-risk men would be as quick to have a prostetectomy as at-risk women seem to be to have mastectomy.

And none of this information considers whether the genes that are associated with increased risk of breast or prostate cancer, when mutated, can increase cancer risk in other tissues. I have argued before that removing the "target" organ may not affect a genetic predisposition to cancer.

Anyway, it will be interesting to see what happens with the new knowledge about prostate cancer.

Marie Godfrey, PhD

What's a family history consultation like?

Last month, the winner of a family history contest in Utah, received his prize: a personal consultation with a family history specialist and genealogist. The story, reported by the company providing the service, is copied below, with permission of the authors, Jim and Mary Petty:

Through the Utah Department of Health’s Chronic Disease Genomics Program, Utahns are encouraged “to know your past to benefit your future”. In the words of the Washington Post (February 26, 2002): “The Family Tree has become the most important genetic test of all. The more you know, the more tools you have to practice preventive medicine.” The Genomics program has promoted the goal “Make Family Health History a Tradition” through a variety of initiatives, publications, and even a contest.

In late 2006 they held the statewide “Tell Us Your Story” contest to motivate the citizenry to learn life-saving family health history information for themselves and their family and then share their story with other Utahns. This contest included an incentive for the winners: those who prepared and submitted an account or essay about what they learned about their family health history and how their family has been impacted by their family health history, might get their story in the newspaper, on the radio, Internet, or even on TV, and 10 lucky winners could win a professional genealogy family history research prize!

HEIRLINES Family History and Genealogy, Inc’s President and career professional genealogist, James W. Petty, AG®, CG (SM) (www.heirlines.com), offered 10 one-hour free consultation sessions (a prize valued @ $150 per winner) at the Family History Library in Salt Lake City, Utah. The success of this unique prize offering is worth sharing.

The first winner of this contest was Eugene, and his wife Rose. Max related how he suffered from a degenerative neurological disorder that restricts his ability to walk. The same condition is in three of his living relatives, and has appeared in his ancestry, first identified with a great grandmother, and an uncle, and other cousins.

Eugene and Rose, and their daughter met with James W. Petty, AG, CG, at the Family History Library in Salt Lake City in the early afternoon of Friday, February 09, 2007, to discuss their family’s interests in Family Health History, and how genealogy research could be conducted to expand their knowledge about their family as well as about the medical affliction that was of such concern to them. Mr. Petty expressed his interest in the situation, but noted very clearly that he was a Professional Genealogy Researcher, and not a medical specialist, or even capable to instruct the family about the medical or scientific aspects of the case, except to offer ideas that could be asked of their medical providers.

The following recommendations were made by Mr. Petty about the genealogy and other issues of concern to the family:

  • The family line in question was on Eugene’s maternal lineage. It was noted that Neurologists treating Eugene, had stated that they did not know the cause of his condition, nor did they even have a name for it. Mr. Petty expressed the opinion that with greater information regarding the extent of the medical condition among Eugene’s extended family, medical science might be able to discover a cause and cure for the affliction. Therefore it was recommended that Eugene’s family, and those willing to work with them, identify all of the descendants of their 3rd Great Grandfather, Thomas, who was the first of the family to settle in Utah with his children. This meant all of the people in the scope of this project would have a Utah origin which would make it easier to find and identify ancestry.
  • Genealogy research in federal, state, local, and church records available at the Family History Library would then help the family identify descendants of their ancestors.
  • Upon identifying the extended family it would be possible to obtain health information about Thomas’s descendants through several sources available to the public. Death records for the State of Utah are now available on the Internet, free of charge at http://historyresearch.utah.gov/indexes. The family can search this site for the deaths of all descendants of their ancestors who died between 1905, when state recorded death records began, and 1954. These records will provide personal and genealogical information, but will also identify the understood cause of death, which might describe a form of the condition that seems prevalent in their family.
  • The next step was to search newspaper obituaries for the State of Utah at either the Family History Library in Salt Lake City, or at the Utah State Archives, or the University of Utah where copies of all newspapers in Utah are available on microfilm. With death dates of ancestors and relatives, obituaries of these people can be seen in the newspapers, which may provide a description of the cause of death (not as commonly found today as it was prior to 1970). This way they may be able to recognize symptoms of the medical condition in other relatives.
  • All of this research would lead the family to discovering living relatives on extended family lines, with whom they could share information and receive information about family health. They might then learn about other relatives with the same medical conditions as they had, and learn additional information that might help their doctors to discover more about their illness.
  • In addition, it was recommended that information about their disease / condition be reported on appropriate Internet message or blog sites. Millions of people across the country read these message boards, and shared discussion of the family’s medical condition might generate discussion with other people experiencing the same condition. This could open up new information that could be shared with the medical specialists who can discover new treatments and cures.

Eugene was very excited about the possibilities this discussion provided him. He recognized that he might not find the cure to his condition in his lifetime, but that his children or grandchildren might genetically carry the condition, and a cure could save them from being bedridden or disabled.

James W. Petty and Heirlines were able to provide guidance regarding family history and genealogy study that would assist these people in discovering their family health history. Neither medical, nor scientific instructions were provided, as Mr. Petty noted that he was not qualified to offer this. However, the professional genealogy information given to the family, did give them encouragement and renewed hope for discovering answers about their family health concerns. They are better prepared to go back to their doctors to work together to find solutions to the disease that has afflicted their family for generations.

Readers will note that I have included the name of the company providing the service--contrary to my usual practice. I am not endorsing this company or its work, just acknowledging the free service they provided.

You can read Eugene's story--and the stories of a number of other people who have had their lives touched by genetics--by clicking on the Your Stories tab at the top of the page. You are also welcome to submit your own story--no names necessary in or after the story, although you will be asked to give us your name and e-mail address so we can confirm that you posted the story and not someone else.

Marie Godfrey, PhD

 

DNA testing and individual people

If you missed it, you should check out the article that appeared in the New York Times written by Amy Harmon. She titled it: My Genome, Myself: Seeking Clues in DNA. Amy writes in a put-it-down-on-as-it-comes-out-of-your-head style not unlike mine, so of course I enjoyed reading it.  

Amy was given the chance--and she accepted it--to be one of the early participants in the $1000 sales of whole genome analysis being offered online by several companies. In my usual policy of not naming specific companies, I'll let you check her article or use a search engine to find one.

Anyway, once her test was in process, she began to wonder how the results would affect her life:

What if I learned I was likely to die young? Or that I might have passed on a rogue gene to my daughter? And more pragmatically, what if an insurance company or an employer used such information against me in the future?

But three weeks later, I was already somewhat addicted to the daily communion with my genes. (Recurring note to self: was this addiction genetic?) For example, my hands hurt the other day. So naturally, I checked my DNA. Was this the first sign that I had inherited the arthritis that gnarled my paternal grandmother?s hard-working fingers?

Using the resources provided her by the testing company, she began to explore her DNA trying to find answers to her "persistent questions". She soon found, as does everyone who looks at the human genome map, or any result from a testing company, that each question generates more questions. Sometimes, you get answers that include predictions:

I was 23 percent less likely to get Type 2 diabetes than most people. And my chance of being paralyzed by multiple sclerosis, almost nil. I was three times more likely than the average person to get Crohn's disease , but my odds were still less than one in a hundred.

Are probabilities divided or multiplied? If you do all the things that would lower your risk of condition X, condition Y, condition Z will you live 110% of your life expectancy?

She dove into the reams of data, doing what we all might do--ignoring the disclaimers along the way:

Compelled to know, I breezed through the warning screens on the site. There would be no definitive information, I read, and new discoveries might reverse whatever I was told. Even if I learned that my risk for developing a disease was high, there might well be nothing to do about it, and, besides, I should not regard this as a medical diagnosis. [I read on:] If, after considering these points, you still wish to view your results, . . . click here. I clicked.

What would you do if you sent in your DNA, paid the $1000, and then tried to interpret the results?

As I've said many times: before you decide to have genetic testing done, consider what you will do with the results. Until you are ready for any possibility--however good or bad or uncertain--save your money.

Marie Godfrey, PhD 

The art of crafting headlines

Today's Google alert for genetics provides over 30 headlines from online services and newspapers around the world trying to get people to read an article about Kaiser--the big insurance company--and its plans to build a monster DNA database from genetic material donated by 2 million people in Northern California.

As often happens, the headlines vary from the plain facts to the extraordinary promises we often see in the field of genetics:

"Kaiser launches genetics study" is the simple title in healthdecisions.org, the Washington Post, Business Week, Houston Chronicle and others.

"Decades long study to probe a range of diseases" states WIFE-TV in Indiana, BruneiDirect in New York, and the Asbury Park Press in New Jersey.

Some sources are more direct in how the study impacts people: "Kaiser asks patients to donate DNA" from Therapeutics Daily tells people that--if they are not patients with Kaiser insurance--they will not be asked to donate DNA.

And then we have the sensational: "Kaiser takes on huge study to help cure killer diseases" from KCBS in California, "Kaiser hopes to unravel some of the biggest medical mysteries" from The Money Times in India, and "New Kaiser Permanente research aims to reveal genetic and environmental causes deadly and disabling diseases" from News-Medical.net.

So, which would you read, if any? And, would you believe 50,000 people or 2 million--both of which appear in news articles.

As a geneticist, I'm thrilled that such work is progressing and will not take money from genetic research funded by NIH or other publicy funded organizations. If I were an optimist, I would imagine all kinds of new and important information about the links between genetics and the environment. The landmark Framingham heart study has added greatly to our knowledge on heart conditions--including the extraordinary idea that women and men are treated differenly when they have a heart condition.

But, as many of you know, I tend to be a pessimist. I look at the "what-ifs" and the potentially detrimental implications of work of this type, such as:

Discrimination against people with "bad" genes or "bad" habits--in insurance and on the job and possibly elsewhere

The release of genetic information from tens of thousands when someone has their laptop stolen with subject data

The remarkable conclusion that genes and the environment interact in determining our health--at the cost of possibly higher insurance premiums across the country

Enough, enough. Such studies are inevitable and your DNA profile will soon be as private as your fingerprint before long. Someone's going to do the DNA studies; it might as well be a company that also holds lots of medical information.  Can you remember how important the 10-year census is to your life? Well, it will go on no matter what you and your POSLQ wish.

As you read about the Kaiser plan--and I hope you do--form your own opinions. And then, post them as comments to this blog. While you're at it, do you live in Northern California or have any relatives that do? Or have you ever been treated in a Kaiser facility? Hmmmm, maybe you're more involved than you thought.

Marie Godfrey, PhD

 

What kinds of genetic tests are available?

There are around 1000 genetic tests currently available; a few of these are marketed directly to consumers. In general, these consumer genetic tests fall into four categories: Paternity, Lineage/Ethnicity, Disease, and Nutrigenomic.

Paternity tests can determine whether one person is related to another person. The most common application of this test is in a paternity dispute. Paternity tests are the most common genetic test sold by online companies. The reason this test is the most popular is because the test itself only costs the customer around $199, and the results are 99.9% accurate. From the perspective of the laboratory, the test is easy to perform, which means they can offer it at a low price. One important aspect of this test is that it does not sequence the customer's DNA directly. It analyzes regions of DNA that do not code for proteins, and thus no medical information can be gleaned from the results of a paternity test.

Lineage and Ethnicity tests are also sold by online companies. These tests trace the ancestry of the customer by analyzing specific genes that have been traced to specific lines of human ancestry. As with paternity tests, no medical information is contained in the results.

Disease tests, on the other hand, are designed to identify specific mutations which are known to cause a certain disease. Several disease tests are available online, which can screen for diseases such as breast cancer, alpha1-antitrypsin disorder, and Hemochromatosis. One important question with these tests is whether they accurately predict the incidence of disease.

Nutrigenomic tests look at genes involved in the everyday operation of the body. Mutations in these genes can result in proteins which function less effectively than normal. In some cases, dietary changes can counteract these defects. For example, a person might have an enzyme that doesn't break down glucose fast enough, leading to high blood sugar level. This information might enable the person to better manage their intake of sugar. There are testing packages for many physiological functions such as bone health, glucose utilization, and stress. The usefulness of nutrigenomic testing depends on whether the effects of the mutations possessed by the individual can actually be reversed through diet or lifestyle changes.

Genetic tests are very accurate if properly administered. However, accuracy is not the only important factor to consider. A highly accurate disease test can show the incidence of a particular mutation, but the predictive value of a test result varies depending on many factors. For example, if a person receives a positive result for a mutation on the BRCA1 gene, this does not necessarily mean that the person has breast cancer. It merely signifies an increased risk of developing breast cancer. Other factors such as ethnicity, lifestyle, and hormone balance, may also play a role in determining whether or not the gene actually leads to the disease state. Although the test may accurately show the presence of mutations, these mutations are usually not the sole determinants of disease. Some disease tests are like this, while others have a higher predictive value. It depends on the disease and the person. Nutrigenomic tests must be interpreted in the same manner. Paternity and lineage tests, on the other hand, are highly accurate simply because there are no other factors. Their predictive value is 99.9%.

A genetic test that can detect whether heart transplant patients are rejecting their donated heart

HealthDay News reported about a simple blood test that can detect whether heart transplant patients are rejecting their donated heart. These patients have an average risk of 3 percent to 5 percent for moderate/severe rejection, and must be monitored for rejection for the rest of their lives. For decades, the heart-muscle biopsy was the most reliable method for detecting rejection. This test may reduce the need for invasive heart-muscle biopsies.

The study by New York-Presbyterian Hospital and Columbia University Medical Center analyzed data from patients in the four-year Cardiac Allograft Rejection Gene Expression Observational Study (CARGO), conducted at eight U.S. transplant centers.

The study looked at a gene expression test called AlloMapT molecular expression testing, which provides information about 20 genes representing molecular pathways in white blood cells found to be associated with heart transplant rejection, as well as information about control genes.

The researchers found that the AlloMap test appeared able to distinguish heart transplant patients who were rejecting their new heart from patients who weren't. The study found that patients with a low AlloMap score had less than 1 percent chance of rejection.

New York-Presbyterian/Columbia will begin offering AlloMap testing to patients on Jan. 1, 2006.

Marie Godfrey, PhD

 

Breast cancer and tamoxifen

A number of genetic tests are available for breast cancer-related genes, and recent news suggests another test could predict responses to tamoxifen. More than 210,000 women in the United States will develop breast cancer. Approximately 70 percent of these cancers are fueled by estrogen, many of which are treated with tamoxifen, a drug designed to block the effects of estrogen in breast tissue. Some women take tamoxifen as a preventative measure against breast cancer.

An enzyme known as CYP2D6 is “responsible for activating tamoxifen to a metabolite called endoxifen that is nearly 100 times more potent as an anti-estrogen than tamoxifen itself,” says James Rae, PhD, research assistant professor of internal medicine at the University of Michigan Medical School. A study of 256 women with breast cancer “suggests that women who inherit a genetic variant in the CYP2D6 gene appear to be at higher risk of relapse when treated with five years of tamoxifen.” Women with this genetic variant (about 10 percent of women) were almost twice as likely to see their breast cancer return.

As always, further studies are needed, but researchers hope this finding may lead to a genetic test--not currently offered clinically. Research is being conducted by the members of the Pharmacogenetics Research Network to confirm whether genetic testing can be used to identify patients likely to respond to endocrine therapy, including tamoxifen. This group is led by David A Flockhart, MD, PhD at Indiana University School of Medicine.

One interesting sidenote in the study was that researchers also found that women with the CYP2D6 variant were less likely to have hot flashes. Any hot flashes among this group tended to be less severe, suggesting that this side effect could predict the gene variation. Ironically, Paxil--a selective serotonin reuptake inhibitors or SSRI used to treat hot flashes--can prevent tamoxifen from being activated. Effexor, another SSRI, does not interfere with tamoxifen’s activation. So, women with breast cancer and hot flashes or depression (SSRIs are also used to treat depression) might be well-advised to confer with their physician on possible drug interactions.

Their findings are published in the Dec. 20 issue of The Journal of Clinical Oncology and were reported by Breast Cancer News online (31 Dec 2005).

Marie Godfrey, PhD

Does ovary removal prevent cancer in women with a BRCA1 or BRCA2 mutation?

The numbers and statistics in the following blog entry are almost guaranteed to confuse you.

The article under discussion here, in the Journal of the American Medical Association, is titled: "Salpingo-oophorectomy and the Risk of Ovarian, Fallopian Tube, and Peritoneal Cancers in Women With a BRCA1 or BRCA2 Mutation." It appears in volume 296, pages 185-192. The original article is available only by subscription or from the authors. Information here comes from the abstract. Definitions are at the end of this entry if you need them.

The authors conclude:

Oophorectomy is associated with reduced risk of ovarian and fallopian tube cancer in high-risk women, although there is a substantial residual risk for peritoneal cancer in BRCA1 and BRCA2 mutation carriers following prophylactic salpingo-oophorectomy.

They also state, in the results:

The overall (adjusted) reduction in cancer risk associated with bilateral oophorectomy is 80% (multivariate hazard ratio = 0.20; 95% confidence interval, 0.07-0.58; P = .003).

O.K., so, according to this article, if you have one of the BRCA mutations, and you have your ovaries and fallopian tubes removed, you can still get ovarian or fallopian tube cancer [???]. You are also still at risk for peritoneal cancer. The 80% reduction in cancer risk sounds pretty good, though. If I hadn't already had my ovaries removed (they didn't tell me whether they removed the fallopian tubes), I'd probably consider this surgery if I were found to have the BRCA1 or BRCA2 mutation.

But what do the study numbers tell us?

1. The study was retrospective--1828 patients with BRCA1 BRCA2 gene were identified from an international registry between 1992 and 2003. Because it is only 2006, it is possible that women identified for the study will develop cancer (or die) in the future--only these occurrences in the past were considered in the analysis of the results. We do not know what will happen to the current "survivors". Also, the abstract doesn't identify how many women were "lost to follow-up" (that is, have data only for part of the study period).

[By the way, those of you worried about genetic privacy, do you wonder what this international registry is and where it gets its data? I certainly do.]

2. The data for the women were first split into those who had no oophorectomy 783/1828 (43%) and those who did: 555 (30%) prior to the study period and 490 (27%) during the study period. O.K. 43 + 30 + 37 = 100%; so far, so good.

3. By the end of the study period, 32 of the 783 women who had not undergone surgery developed cancers [the abstract doesn't say what type, but ovarian, fallopian tube, or peritoneal is implied]. This is reported, not as 32/783 (4.1%), but as 1015/100 000 per year.

4. Of the women who had undergone surgery, eleven cancer cases were identified at the time of prophylactic oophorectomy and 7 were diagnosed following prophylactic oophorectomy. This is reported in the abstract as 217/100 000 per year. The fraction 18/1045 (11 + 7 = 18 and 555 + 490 = 1045) is 1.7%.

5. If you compared 4.1% with 1.7% (over the short course of the study), you might say that among women with a BRCA1 or BRCA2 mutation, those who had no surgery (oophorectomy) were 2.4 times as likely to develop cancer compared with women who had prophylactic (pre-emptive) surgery (4.1 divided by 1.7). [Note that the wording is "as likely", not "more likely".]

6. If you compared the per-year numbers 1015 vs. 217, you could say 5 times as likely (1015 divided by 217).

7. If you did a "survival analysis" [as the authors did], you would find "The overall (adjusted) reduction in cancer risk associated with bilateral oophorectomy is 80% (multivariate hazard ratio = 0.20; 95% confidence interval, 0.07-0.58; P = .003)."

So, which is the "real" number?

Just one more set of numbers: Only about 5-8% of women have a mutation in the BRCA1 or BRCA2 genes. Many sources report that mutations of the BRCA1 and BRCA2 genes give women a higher risk of developing ovarian cancer (15 percent to 54 percent), than women without the mutation.

So . . . do you have a test for BRCA1 and BRCA2? . If you find out you have one or more mutations in these genes, do you have the removal surgery? If so, have you now eliminated your chances of having ovarian, fallopian tube, or peritoneal cancer? The answer is, No.

The purpose of spouting all these numbers is to help you understand that news articles select the numbers that seem simplest to them; the deeper you dig, the more likely you are to wonder about the validity and practicality of those numbers.

Marie Godfrey, PhD

Definitions: Salpingo-oophorectomy--removal of ovaries and fallopian tubes. Peritoneal-- the peritoneum is a membrane that forms a sort of envelope around your abdominal organs and also lines your abdominal cavity

Genetic testing and breast cancer

Many other women who are related are learning, thanks to genetic testing, that they share a strong potential for being hit with breast or ovarian cancer in their future. Some of these women are choosing mastectomies, ovarectomies, and hysterectomies to remove the potentially susceptible tissue and dramatically reduce their chances of having cancer of the breast, ovary, or uterus.

One recent story from the Associated Press, published at http://kvoa.com/Global/story.asp?S=4776478, described Mindy Diamond-Rivera, a 47-year -old woman in Arizona who had her breasts removed and "is ready to get rid of her ovaries and uterus." Last September, she learned that her chances of breast cancer were 87%--a striking confirmation of the family history she's been afraid of since her mother, grandmother, and great-grandmother all died of breast cancer before 43. Taking no further chances, she had her breasts removed last November. Because having the BRCA-1 gene also predicts that her chances of having ovarian cancer are 60%, she intends to have her ovaries removed--and her uterus. "Everything's coming out", she says. According to the article, "Her insurance has covered almost everything so far. Most insurance companies cover about 80 percent of the genetic testing, said genetic counselor Jessica Ray [of the High-Risk Breast and Ovarian Cancer Clinic at the Arizona Cancer Center]. The cost of the test without insurance is $2,975."

New test available for sensitivity to a colon cancer treatment

According to news from The Mayo Clinic, a genetic screening test that can determine which patients are likely to have a serious adverse reaction to Camptosar® (irinotecan hydrochloride), a key component of standard first-line therapy for advanced colon and rectal cancers. An article at http://www.emaxhealth.com/51/4752.html describes the details.

According to Mayo Clinic medical oncologist Matthew Goetz, M.D. who was quoted in the article, "Irinotecan is an important treatment approved by the FDA for patients with colon and rectal cancers, but its side effects can be dangerous or even lethal in up to 30 percent of the population." The UGT1A1 test--which looks for a mutation in the gene that helps a patient metabolize irinotecan, was approved by the FDA in August; licensing agreements have just been finalized. If a patient has the mutated gene, dosing of irinotecan would have to be reduced or even eliminated to avoid serious side effects.



According to the article, "This kind of customized dosing approach based on a person's genetic makeup is known as pharmacogenomics and is the newest frontier of 21st century medicine." Dr. Goetz adds that the application of this test for patients with colon and rectal cancer may only be the beginning. "Irinotecan also is being tested and used for other cancers, such as cancers of the GI tract, as well as lung and breast carcinoma,"

Because the UGT1A1 pathway is also important in the metabolism of other drugs, the test may be useful for managing potentially serious side effects of some other drugs also. The test kits are available from the Mayo Clinic, through your physician or other healthcare provider. The test is not being sold directly to consumers.

Marie Godfrey, PhD


 

 

 

Predictive genetic testing and cancer

Predictive genetic testing may help identify people who are at an increased risk for developing certain types of cancer. While this type of testing may indicate the absence or presence of a gene thought to be associated with a specific cancer (for example, the BRCA1 gene and one form of breast cancer), testing also carries many limitations and risks. Before undergoing genetic testing, you need to fully understand the process and its implications. here are some items to consider.

An accurate test may produce a positive, negative, or ambiguous result, but it cannot guarantee that a person will or will not develop cancer. As thorough a knowledge as possible of family history is perhaps the most important part of any genetic test. However, people with no information on their potential cancer ancestry can still learn some things from genetic testing. In the latter case, a person's pertinent genetic makeup can be compared to others in the general population or with similar ethnic ancestry.

Many experts recommend undergoing genetic testing only when a pedigree analysis suggests the presence of an inherited cancer syndrome for which a specific mutation has been identified. Other guidelines suggest that genetic testing should be pursued only when the test will impact future medical care and decisions.

Besides family history, another important element of genetic testing is the assistance of a genetic counselor. Generally, your family doctor has neither the knowledge nor the time to provide all the assistance you may need. Your doctor may, however, be able to help you find a counselor and arrange for testing and support.

Marie Godfrey, PhD 

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Tests related to colon cancer

There are three basic tests that I know of, in addition to at least three types of examinations.

1. Hemoccult test--this one has been around for a while. It is a take-home test, sometimes availale from your pharmacist or the American Cancer Society. The test is free. The test kit consists of three pieces of filter paper, on which you smear three small stool samples, taken at different times. You send the kit in for analysis and receive results by mail. The test looks for occult (hidden) blood, which may have come from a cancer in the colon. Since there are a number of other reasons to have blood in your stool (hemorroids for example). A positive test result simply means there is more testing to do.

2. The test I described a couple of days ago is a genetic test for the existance of cancer. Some colon cancers are associated with one or more of three genetic mutations. The test, which you can purchase over the Internet, looks for these mutations in cells within a stool sample. I believe the test is quite expensive. If you think you'd like to try this test, I would recommend consulting a physician. Insurance is more likely to cover the test that way.

3. Another test is a predictive test: do you have the genetic mutation that results in more frequent polyp formation in the colon? Approximately 5-10 percent of colon cancers are associated with this mutation and as many as 80 percent of people with this mutation may develop colon cancer. This test is also available over the Internet, but I recommend a physician's support is here also.

Then, there are the "physical" exams: sigmoidoscopy and colonoscopy. In both cases, the preparation for the exams is worse than the exam itself. If you are over 50, you should have the colonoscopy at least every 10 years, more often if you have a tendency to form polyps or a family history of forming polyps. A sigmoidoscopy is generally less extensive than a colonoscopy; to me there's no logical reason to do the lesser of the exams. I believe it was more popular when exams were done without a sedative and were often painful. The colonoscopy is performed when you are sedated and the physician performing the exam can take photographs/videos for comparison with later tests. If polyps are found during the exam, they can be removed and tested for malignancy. The prep? You have to clean out the colon for the examination. This means drinking a fluid to stimulate evacuation and staying near a bathroom.

The third test is a "virtual" colonoscopy. I believe it involves getting a miniature camera into the colon--by swallowing a gelatin-coated pill--and then picking up the transmissions from the camera. I'll have to check this one out further, because I haven't heard much about it lately, and don't know if it's still being used, and if it is, how the whole process works.

To learn more about any of these tests, check out the American Cancer Society's site. Remember that the organization is somewhat conservative and generaly recommends only the most tested exams, not listing newly developed tests or exams until they have been clearly shown to benefit people.

If you have a specific question about a test or exam, or about the genetics of colon cancer, please use the comment mode to ask your question. You do not have to give your name.

Marie Godfrey, PhD

What is the difference between a genetic test ordered by a consumer and a test ordered through a doctor?

The convenience of ordering a genetic test via the Internet may seem tempting, but at the current time there are a lot of unknowns. Consulting with a healthcare professional has many advantages. For example, a patient may believe they should take a test even though there is no evidence of disease. In this situation, a doctor could prevent the patient from wasting a significant amount of money on a genetic test they don't need.

In addition, an online testing company does not require proof of identification when doing a genetic test. As a result, a customer could send in another person's DNA sample raising privacy concerns. Doctor involvement allows for better privacy protections by ensuring that your DNA falls under the Health Information Privacy Protection Act (HIPPA), not the jursidiction of a lab that resides in a state with unknown consumer privacy laws.

A health care professional can also help with interpreting the test results and understanding the limitations of genetic testing. It's likely that if a physician or a genetic counselor is not part of that process, you won't be getting the best care possible.

Suggested reading: Too Much Information: Results of Home DNA Tests Can Shock, Misinform Some Users

 

 

What is the impact of genetic testing on privacy?

"Genetic testing appears to exist in a regulatory vacuum," according to the policy director of the Genetics and Public Policy Center at Johns Hopkins. Because of the difficulty of performing and interpreting genetic tests, the labs which perform the approximately 1,000 tests currently available are not well (if at all) regulated at either the Federal or state level. Indeed, almost none have been reviewed by any government agency to ensure they do what they say they do. The FTC (Federal Trade Commission) regulates how genetic tests are advertised to consumers but none have been enforced yet with respect to the advertising of genetic tests. The FDA (Food and Drug Administration) regulates genetic test kits, but, according to Javitt, most gene testing labs develop their own in-house methods that are not currently reviewed by FDA. Even laboratories certified by CLIA (Clinical Laboratory Improvement Amendments) which covers basic and generic lab practice issues, does not provide information that is relevant to disease or future disease or condition.

With regard to privacy, there is no comprehensive federal protection in place. At the state level, privacy/discrimination legislation is variable, at best. For example, a consumer in Oregon purchases a genetic test from DNADirect (an online vendor based in San Francisco, CA). The consumer sends in their DNA sample to be tested. As soon as the sample leaves the state it is no longer protected under Oregon's genetic privacy laws. DNADirect sends the sample to Myriad Genetics, a laboratory in New Mexico, for testing. Since New Mexico currently does not have specific laws protecting the privacy of genetic information--and since the sample is no longer under Oregon jurisdiction--maintaining the privacy of the sample (and the donor) may be at-risk. At the present time, several other U.S. genetic testing labs, notably, Florida, California, and Ohio, also have no legislation which speaks directlly to protecting the privacy of genetic information.

For all of the above reasons, raising your awareness and understanding of the regulatory state of genetics and genetic testing in your state is important.

Consumer Considerations:

  • Genetic tests ordered through a doctor provide for better privacy protection.
  • Increasing the circulation of genetic and other health information through unregulated channels may increase the potential for unwarranted invasions of privacy and genetic discrimination.
  • Policymakers have been slow to enact blanket genetic privacy protections and the protections currently in place provide no solid protection for individuals.

How safe is your genetic information?

If you choose to have a genetic test purchased online from one of the many companies offering them, you may be concerned about the privacy of your genetic information. Check the website and the information you receive to learn what the company's policies are.

If, on the other hand, your genetic information is becoming part of a database covered by HIPAA (Health Insurance Portability and Accountability Act), you may be interested in how secure your information is when "protected" by the federal government. The Washington Post, in an article today titled "Medical Privacy Law Nets No Fines" starts this way:

In the three years since Americans gained federal protection for their private medical information, the Bush administration has received thousands of complaints alleging violations but has not imposed a single civil fine and has prosecuted just two criminal cases.

Of the 19,420 grievances lodged so far, the most common allegations have been that personal medical details were wrongly revealed, information was poorly protected, more details were disclosed than necessary, proper authorization was not obtained or patients were frustrated getting their own records.

More than 14,000 of the cases are considered "closed", either because no violation was found, or the group accused of violation (hospital or physican, for example) agreed to fix the problem. No one's watching, though, to see they do.

According to the article,

At least 309 possible criminal violations to the Justice Department. Officials there would not comment on the status of those cases other than to say they would have been sent to offices of U.S. attorneys or the FBI for investigation. Two cases have resulted in criminal charges: A Seattle man was sentenced to 16 months in prison in 2004 for stealing credit card information from a cancer patient, and a Texas woman was convicted in March of selling an FBI agent's medical records.

Advocates for personal privacy suggest that "the lack of civil fines has sent a clear message that health organizations have little to fear if they violate HIPAA."

To read more, check out the article at http://www.washingtonpost.com/wp-dyn/content/article/2006/06/04/AR2006060400672.html

Marie Godfrey, PhD

Privacy of medical information threatened

I haven't been watching the House and Senate daily since stem cells were dropped from the agenda, but today I was reminded that's not a good thing to do. While you're not looking, Congress may slip something through you had no idea about.

This time it could be the privacy of your personal medical information (including results of genetic testing).

I received a notice from the Ethics and Health Law daily newsletter, which happens to come from Australia. The lead-in said: "Congress has latched onto legislation to create a national health information system: the Health Information Technology Promotion Act of 2005 (HR 4157)." and the source was given as Medical News today, 11 February 2006 (http://www.medicalnewstoday.com/medicalnews.php?newsid=37575#)

Oddly enough, the bill in question was introduced in October of last year; it didn't reach the news, but did catch the eye of the Citizens' Council on Health Care (CCHC). According to the article,

"This bill gives the federal government complete control over private medical data. It advances a national health surveillance system - a system where the patient's data is shared, assessed, analyzed, collected, and used without the patient's consent or knowledge," said Twila Brase, president of CCHC.

She clarified, "If this bill passes, there will be no virtually no escape for the public. The so-called federal medical privacy rule (HIPAA) eliminated patient consent requirements. This bill allows the federal government to gut stronger state privacy laws. Together they will lead to the end of personal and medical privacy for all American citizens." 
 

CCHC has published a chart, including analysis of the bill language and implications for the public if HR 4157 passes, click here to see it.

If you're interested in the privacy of your medical information, you may want to check this out. At the moment, the bill is still in committee.

Marie Godfrey, PhD

What is the role of the primary care physician in regards to genetic testing?

Members of the general public have historically turned to their primary care physicians with questions about inheritable conditions. As the availablility of genetic tests increases and direct-to-consumer advertising of genetic tests becomes more pervasive, family physicians should expect:

  • an increase in the number of requests for genetic tests from their patients;
  • an increase in the usage of genetic tests for health care planning and decision making;
  • an increase in the number of patients who order and interpret genetic tests without consulting their doctor

Today’s family physicians need to know not just about the availability and reliability of specific genetic tests but also to understand the implications of their use. These will include:

  • genetic testing for untreatable conditions;
  • requests for prenatal diagnosis of adult-onset inherited conditions;
  • when to test and who should pay;
  • misperceptions about genetic privacy, informed consent, use of health information records and DNA (tissue samples);
  • the ability of Federal and state statutes to protect patients from possible insurance and/or workplace discrimination;
  • implications of genetic testing for the families;
  • doctors must help patients make difficult treatment decisions based on incomplete or uncertain information about future conditions.

Strategies to help patients understand risk

Here's where to find the article on "Strategies to help patients understand risks":

http://bmj.bmjjournals.com/cgi/content/full/327/7417/745

You will have to download the pdf (Adobe) file.

Ancestry searches--do we only go for "far enough"?

Sometimes I wonder what people are thinking when they decide to research their ancestry. Is the goal finding someone important? Validating family stories? Proving connections to a particular "race"?

In the recent Newsweek article and the program on PBS, African-Americans, at least one person received different information about their ancestors than they were expecting. Most notable to me was the "Black man" who found he had no African heritage at all. A person whose letter was published in this week's Newsweek asked why nothing was said about repeating the surprised man's tests. That means that several others noticed that none of the presentations spoke about possible incorrect results.

Also interesting was the person who suddenly started wearing a Star of David upon learning of his Jewish heritage. This certainly suggests that some people change their behavior as a result of genetic testing--regardless of the accuracy of those tests. The common test sold in grocery and variety stores--the one that comes from Sciona--was featured several years ago in GeneWatch as a dubious product. Of course, the producers of Newsweek and PBS didn't identify the companies that did the tests. And we probably wouldn't have wanted that, considering the benefits of such free advertising.

Anyway, back to my main idea. What makes people trace their ancestry with a genetic test and when in the process do they stop? Anthropology and archealogy would both say that going "all the way back" brings us to an origin in Africa. But, many people stop once they've connected with a solid European (especially Western) heritage. If genetic tests are so good at telling people where they came from, how come they're comparing your DNA to someone's DNA collected in the past 10 years or so? Do we think that genetic changes occur worldwide and through time but can be ignored when the results say we're part of a group living today? Sounds a bit inconsistent to me.

By the way, just as with the chimpanzees, the differences between so-called races (or between chimps and humans) are many-fold smaller than the differences between two "Western European Caucasians" (or humans or chimps). Isn't amazing how we weight visible differences or even non-obvious differences (such as native language) much more than we do invisible factors?

Marie Godfrey, PhD

Genetic testing and family relationships

A public television special on African-Americans included some small pieces on genetic testing as it is used to test family relationships. The Feb 6 issue of Newsweek has more and presents some visual aids. In addition, a live talk featured Claudia Kalb answering questions about genetic testing. Of the three, the Kalb live talk was the only one allowing public participation. Since I thought some of you might be interested, I am attaching a copy of Kalb's transcript here. Among other things, it gives us an idea of why people are so interested in genetic testing.  Note that the genetic testing discussed focuses only on family interrelationships and not on diseases or conditions with genetic components.

Marie Godfrey, PhD

Can the results of a genetic test be used to deny insurance coverage?

Although most states (47) have laws in place prohibiting the use of genetic information in denying health insurance coverage, these laws do not generally apply to self-insured people or to companies with fewer than 50 employees. On the other side of the picture—insurance coverage of genetic testing—state laws focus primarily on state-mandated testing of newborns. According to Alissa Johnson of the National Conference of State Legislatures, “no state requires health insurance coverage of genetic testing for adult onset disorders, such as breast cancer, which may cost more than a thousand dollars.”

She suggests that legislators investigate the benefits of genetic screening and the potential benefit to individuals or families being tested. Addressing the inequalities in ability to pay for genetic testing, she states that “affordable access to these services may still be in the distant future.”

Aetna Chairman and CEO John W. Rowe, M.D., in a speech several years ago, recommended that the health insurance industry support legislation and consider adopting guidelines for access to genetic counseling and genetic testing. He suggested the following approaches:  

  • Cover genetic testing in individuals shown to be at risk where results may affect the course of treatment of the insured.
  • Cover genetic testing for a family member where the family member is not otherwise insured, and results may affect the course of treatment of an at-risk insured.
  • Cover consultation with qualified counselors and physicians, and facilitate the appropriate interpretation of genetic testing results.
  • Support physician education in the appropriate interpretation and use of genetic tests, including guidance in selection of medication (pharmacogenetics).

Sources: http://www.ncsl.org/programs/health/genetics/geneticshins2004.htm and http://www.aetna.com/news/2002/pr_20020617.htm

Marie Godfrey, PhD 

Can the true nature of race be revealed through genetic testing?

The text below comes verbatim from an excellent article I received through my genetic testing Google alerts. You can find the original at http://news.ncmonline.com/news/view_article.html Genetic Drift: The True Nature of Race Colorlines, News Report, Ziba Kashef, Posted: Nov 11, 2007 Ever since scientists discovered “the secret of life” embedded in our DNA a half century ago, the study of human genes has sparked debate about the nature of race. The question seemed to be settled in the early 1970s when biologist Richard Lewontin compared variations in genes within and among different population groups. His conclusion, that most human genetic variation did not fall along racial lines, was widely accepted. At the molecular level, human beings are more alike than different. Repeat experiments confirmed this finding, and many experts embraced the knowledge that the racial categories that have long divided people and justified racist oppression represented social and political beliefs rather than biological truths. But the notion that race is real as a biological fact did not die. Even after research teams who identified and sequenced all 20,000-25,000 genes as part of the historic Human Genome Project declared in 2000 that race was not a valid scientific concept, the counterclaim resurfaced. Ironically, the more science has delved into the intricacies of our DNA, the more experts have diverged on the question of race. The dispute, which reverberates mostly in the pages of academic journals and in the halls of some of our most prestigious institutions, could have negative repercussions in the real world for communities of color. From criminal justice to medical research and genealogy, the lack of clarity on the true nature of race poses risks, including the risk that, as a society, we might start believing in essentialist notions of race again. While acknowledging that science is often used for positive purposes, including ones that benefit communities of color, social justice advocates must remain vigilant. All technologies, including new genetic technologies, develop in a political, economic and social context, says Patricia Berne of the Center for Genetics and Society, a public affairs nonprofit based in Oakland, California. “The broader political left has not really grappled with the ways these technologies affect our claim to resources, our claim to rights, and the well-being of our communities,” she notes. Before race is resurrected and redefined by biologists, geneticists and biotech firms, social justice advocates must grapple with the issues and add their voices to the debate. FORENSICS This spring, the New York Times published a startling article entitled “The DNA 200,” a brief piece with a collection of thumbnail-size photos of former inmates who had been released on the basis of DNA evidence. A quick survey of the images was compelling—most of the faces were Black and brown men who had spent an average of 12 years behind bars for crimes they had not committed. Each face and each exonerated individual represented a victory for the Innocence Project, an 18-year-old legal advocacy group that works to reopen old cases and change lives with the help of DNA evidence. For these men, DNA analysis helped prove, without a shadow of doubt, that genetic material uncovered at a crime scene did not match their own. Science was an instrument of justice. But just as easily, DNA can be turned into a high-tech tool for racial profiling, although on shakier scientific grounds. It led to the 2004 conviction of an African American suspected of multiple serial murders in Baton Rouge, Louisiana. Initially, police sought a white suspect, based on eyewitness testimony and the assumption that most serial killers are Caucasian. But the case took a turn when a technology firm, DNA Print Genomics, offered to analyze the sample from the crime scene. Their test concluded that the suspect was “85 percent sub-Saharan African and 15 percent Native American” and therefore medium- to dark-skinned black, not white. It appeared to match a sample given to police voluntarily by Derrick Todd Lee, a man with a history of legal troubles. Lee’s conviction and death sentence were based in part on a method that critics say is at best a prediction of geographical ancestry—not a 100-percent certainty. The stockpiling of DNA samples from suspects and convicts has become the norm in many states. Even the liberal governor of New York, Eliot Spitzer, recently proposed expanding the DNA database there to include individuals convicted of misdemeanors such as minor drug violations and unlawful credit card use. Virginia also collects the DNA of nonviolent offenders, and Louisiana requires samples from those who are simply arrested for a felony. Previously, DNA had been collected only from those found guilty of the worst crimes. Spitzer’s proposal is supposed to make it easier for prosecutors to lock up more criminals and for the wrongly accused to prove their innocence. But given the racially biased arrest and conviction patterns of New York and other states across the country, the consequences are likely to disadvantage people of color. As databases mushroom, the development of genetic racial profiles may be the next wave in law enforcement. DNAPrint claims the ability to use DNA to “predict” physical features such as skin and eye color, adding more and more detail to a genetic sketch. Their web site boasts 100 percent accuracy in blind, company-administered tests. But one critic pointed out that since the test that identified the Baton Rouge killer estimated the percentage of ancestry from four groups that mostly include dark-skinned individuals (sub-Saharan Africans, East Asians, Indo-Europeans, Native Americans), any prediction would inevitably fall into one or more of those ethnic groups. The company provides a separate screening test for additional groups, such as Northwestern and Southeastern Europeans, Middle Eastern and South Asian, but less commonly. Such racialized forensics presents multiple problems for people of color. It blurs the line between DNA tests that can definitively rule out suspects (as in the Innocence Project) and less certain analyses that “predict” or state the probability of a match. It gives scientific legitimacy to the widespread but still controversial notion that certain genetic differences, or markers, correlate precisely with geographic regions and modern racial categories. Further, it makes acceptable manhunts for “ancestry informative markers,” a euphemism for racial identifiers in genes despite the many pitfalls of old-fashioned racial profiling. Worse still, it creates a market for a growing list of genetic services that may, at best, be good guesses but not definitive. Critics fear that such questionable science in criminal justice will inevitably lead to searches for gene markers for criminal behavior. If criminologists start with a database that is disproportionately Black and Latino because of police practices that target those communities, any computer-generated findings will be skewed. “What you’re dealing with is a population in the database which is distorted,” says Troy Duster, a sociologist and chancellor’s professor at UC Berkeley. “So if someone wants to do this kind of research, they’ll look for genetic markers. What they’ll find, of course, are certain markers. Tell the program to find markers and you can find markers in DNA that may be more or less likely to appear in populations A, B or C. But it will be a huge mistake to conclude that because you have those markers you’ve explained crime.” The ever-expanding databases give law enforcement a powerful, high-tech tool. With each DNA sample, government seizes personal biographical information, stripping citizens of their privacy rights. Since each sample offers clues not only about individuals but their relatives as well, entire families are open to scrutiny. In some cases, once a DNA sample is taken it is not destroyed or returned but stored indefinitely, unless the law in a particular state stipulates otherwise. MEDICAL RESEARCH Genetic science is similarly double-edged in the realm of health research. As scientists were busy mapping the human genome in the early ‘90s, for the first time the government moved to mandate that all federally funded biomedical and behavioral research include members of historically excluded groups: minorities and women. After decades of research on mostly white, male subjects, this development—pushed both by Black politicians and women scientists—was generally hailed as an advancement. Documenting health disparities is indeed an imperative, given the much higher rates of disease and mortality from disease among ethnic minority groups in the United States. But the mandate had at least a few notable detractors. As it was to take effect, a handful of African American scientists voiced opposition, according to Duana Fullwiley of Harvard, who recently published “The Molecularization of Race” in the journal Science as Culture. Dissenter Otis Brawley, formerly at the National Cancer Institute, wrote: “The legislation’s emphasis on potential racial differences fosters the racism that its creators want to abrogate by establishing government-sponsored research on the basis of the belief that there are significant biological differences among the races.” But by the time Brawley and others registered their complaint, the train had already left the station. The use of racial categories in applications for research funding and reporting of results had become the accepted norm. Paradoxically, as the Human Genome Project discredited the use of race in science, the pharmaceutical industry moved in the opposite direction, according to Fullwiley. Instead of focusing on the 99.9 percent overlap in all human genes, the Pharmacogenetics Research Network, a government funded follow-up to the Genome Project, honed in on the 0.01 percent difference as a source of the new discoveries and therapies. And several scientists and researchers sought further funding for investigations into possible genetic causes for racial disparities in disease and drug responses. Their faulty reasoning, however, is illustrated by the controversial race drug BiDil. Developed to address the greater mortality from heart failure among African Americans, the drug has been met with both celebration and skepticism. While it is true that Blacks ages 45 to 64 are more than twice as likely to die from heart failure than whites, Duster points out that the disparity narrows after age 65. The disparity may have less to do with biology and race than other documented factors in heart disease, such as diet, stress and lifestyle. Evidence outside of the U.S. also undermines the rationale for a race-based approach to the condition. Citing the data of epidemiologist Richard S. Cooper, who compared hypertension rates worldwide, Duster explains, “Germany has the highest rate of hypertension, and Nigeria has the lowest rate. It doesn’t take a Ph.D. in epidemiology to figure out what might be the issue there. It can’t be race and genetics.” Scientists do, of course, acknowledge the influence of environment and lifestyle on disease and disparities. The laser-like focus on, and blind faith in, genes as the source of understanding and treating disease has been tempered by technical challenges and other trends in medicine. But the damage to our society’s understanding of race may be done. As federal dollars continue to flow to research on the genetic basis for certain racial disparities—in diabetes, asthma, alcoholism and other conditions—race as a biological fact becomes more solidified in public consciousness, and the socioeconomic factors in disease get obscured. “It takes the issue in a crude way and focuses it on what’s going on inside the body,” says Duster. “[But] if you say, well, maybe there is a complex interaction between environment and disease, then the answer is going to be primarily outside the body.” Even if more race-specific medicines and therapies are developed from pharmacogenetic research, it’s unclear whether those treatments will actually alleviate disparities. Most diseases that disproportionately afflict African Americans and other ethnic groups—heart disease, cancer, diabetes—are not caused primarily by single genes or even clusters of genes. Even in cases where illness is linked to specific genes, like sickle cell disease, no miracle cures are forthcoming. With less access to health insurance and health care, people of color may not have access to new treatments or the personalized medicine that remains the goal of many genetic scientists. GENEALOGY Another area where genetics and race collide is genealogy. Curiosity about our origins has motivated countless Americans, including people of color, to have their DNA tested and compared with samples from around the world. Dozens of companies have met the demand with genealogy services that charge a fee for collecting samples, analyzing results and providing answers to questions about family history. In a famous case, the descendants of Sally Hemings, who as a slave had a relationship and son with Thomas Jefferson, used DNA testing to prove they were indeed related to the Founding Father, despite denials from Jefferson’s white descendants. More recently, media mogul Oprah Winfrey declared that a DNA test had shown that she was Zulu. But Winfrey’s case is an example of the false confidence many people place in the results of ancestry testing. DNA analysis of ancestry typically traces DNA along one of two lines—the paternal Y chromosome or maternal mitochondrial line. It can give people accurate information about their father and father’s father, or mother’s mother and so on (thus conferring accuracy to the Hemings/Jefferson test). But each individual’s family tree is much greater than one line. If you go back four generations, you have 16 ancestors—but the testing only provides details about one of them, capturing only a partial picture of lineage. Further, while Winfrey’s genetic sample appeared to match the DNA of others identified as Zulu, the term describes a cultural and linguistic group that coalesced sometime after slaves were taken primarily from West Africa to the Americas. The science gets even more questionable when researchers and biotech firms attempt to draw conclusions about the ancient ancestry of entire groups. Two years ago, the National Geographic Society and IBM announced an ambitious project to collect more than 100,000 samples of DNA from indigenous people worldwide. The plan, known as the Genographic Project, was to use the DNA, collected from cheek swabs, to study ancient migration patterns and learn more about where different populations originated. With $55 million in funding and 10 centers based globally, the project was poised to amass, as its web site states, the largest DNA database of its kind in the world. But the project’s methodology is no more precise than other ancestry testing services. It also uses proprietary computer programs to trace either paternal or maternal lines, leaving a majority of an individual’s ancestors out of the analysis. It assumes that certain indigenous populations have been isolated and their genes not complicated by migration and mixing with other populations—an assumption many Native Americans challenge. The project also conflates geography with ancestry and culture, which can be easily interpreted as race. From its inception, the project has met with resistance from several indigenous groups. Though some have participated, most North American tribes and nations have declined. Given the history of scientific racism, indigenous people are wary of the project’s intentions and consequences. While scientists stand to gain knowledge, and career advancement, from research on indigenous people, those populations potentially have a lot to lose. For example, the project poses questions about the aboriginal inhabitants of various regions and countries, and if it were to conclude that groups in Alaska came from Asia or elsewhere, the research could be used to undermine indigenous claims to land and other rights. “Governments have a long history of trying to divest indigenous peoples of their land rights and undermine their cultural integrity,” says Debra Harry, executive director of the Indigenous People’s Council on Biocolonialism, which opposes the project. The terms “ancestry” and “genetic diversity” have emerged as alternative ways to describe the differences we know as race. But they may be no more accurate in expressing human genetic variation than traditional racial categories are. Genetic markers attributed to one group or region of the world can be found in others. Whether scientists discuss the variations in terms of geography or ancestry, the impact will be the same: resurrecting race and racial differences as concrete biological facts, encoded deep within our DNA, and confirmed by science. Ziba Kashef writes frequently about health and race issues. Her work has appeared in Real Health, NMA Healthy Living, Essence and other publications.

Can you use your DNA to "buy" racial identity?

The Daily Bruin, a UCLA newspaper, writes about some interesting motives for DNA testing: the attempt to identify yourself--or perhaps your children--as members of a particular ethnic group for the purpose of getting past racial quotas for college entry, for financial aid, or for tapping into some of the money generated from American Inidan casinos. Some are even trying to claim Israeli citizenship on the basis of a genetic test result.

The article chides those who chose this path:

Systems of racial preference are praiseworthy but plagued by the fact that racial identity is impossible to quantify. Manipulation of such systems is not only shameless, it also undermines them. And to further complicate the issue, these ethnic ancestry tests have a margin of error that scientists say can be misleading.

Science should be used for the pursuit of knowledge, not personal advancement within any possible loophole. It would be naive to expect people to ignore opportunities that would give them better pay or entrance into a better school; on the other hand, corporate employers and college admissions officials can't do anything about it without taking on the hazy task of assigning a numerical value to that which makes someone a certain race.

The very idea that one can test out of, or into, belonging to a particular race is fundamentally flawed. These genetic tests are applying an absolute science to something that is far too personal to be measured empirically. In addition, if you're at the point where you're taking a test to see if you are a member of a specific race, then you probably don't identify with that race in the first place.

Moreover, testing might be able to create a balanced genetic breakdown of all students in an incoming class, but it does not guarantee a diversity of ideas and perspectives. Isn't that the purpose of having individuals from different ethnic backgrounds, especially in an academic setting?

While working on an issue about modern tribal members for a magazine called Oregon's Future (www.oregonsfuture.org), I learned that tribes in the Northwest do not consider a person a tribal member on the basis of a DNA test alone--cultural connections are key. Some tribes even require that you live on tribal land.

They conclude:

This latest case of DNA testing highlights the problem of defining race.

Increasingly in the United States, race is a set of experiences with which one identifies, not a matter of fractional ancestries.

Marie Godfrey, PhD

Check out your risk for breast or colon cancer before considering genetic testing

Having just completed a colonscopy--I was told that Medicare doesn't pay for the procedure and I'll be going on Medicare in a few months--I was naturally glad to hear that I am "normal". Wondering what factors other than genetics might affect my susceptibility to colon cancer, I was immediately interested in an article from KSL.com, the website of my local newspaper. I won't send you to the article, because it leaves out the most important information--how to find the website with the "new web-based program [that] can help you find out if you should seek out genetic testing." I checked out the Dana Farber link (www.yourdiseaserisk.harvard.edu) and found an interesting test for colon cancer--and others for breast cancer, heart disease, etc. I took the colon cancer test and found that my risk is below average. The test also told me what to do to decrease my risk. However, since there was essentially no mention of genetics, I may not have found the right site. We'll see if anyone responds to my question to KSL. If I find out more, I'll let you know. Marie Godfrey, PhD

Does genetic testing from different labs yield the same result?

I have often remarked that different genetic testing laboratories may give different results and suggested that people not automatically accept the results of one laboratory when planning their futures. This is especially true when major life decisions are involved.

A recent report from the IOS Press, published online by newswise introduces the situation for a specific genetic test as follows:

For individuals who develop colorectal cancers at a young age or have a family history of such cancers, microsatellite instability testing (MSI) has become an almost standard component of clinical evaluation. This DNA-based test can uncover hereditary nonpolyposis colon cancer syndrome (HNPCC), also called Lynch’s syndrome. However, despite the increased use of this test, there have been no reports of how well the results from any given laboratory agree with any other laboratory. In an article in the current issue of Cancer Biomarkers, researchers conducted testing across 6 laboratories to evaluate variability in reported results.

Here's what was done:

The six laboratories, located in the United States, Canada, and Australia, were members of the Cooperative Family Registry for Colon Cancer Studies (also called the Colon CFR). Using tumor samples collected since 1998 through the CFR, MSI testing was done at the six laboratories. Three of the laboratories had more than 8 years each of prior experience in MSI testing, while the other three set up MSI assays specifically for the Colon CFR.

The results--and follow-up--were very interesting:

When the result showed wide disagreement with no systematic trends, one of the most experienced laboratories was designated the “gold standard” reference facility. With further testing of samples among the most experienced laboratories, the credentials of the reference laboratory were validated. A review of the results from all of the facilities resulted in five key rules that laboratories should observe when conducting MSI testing. Using these lessons learned, a final set of testing showed much improved agreement across all six laboratories.

The complete article, “Ascending the Learning Curve – MSI Testing Experience of a Six-Laboratory Consortium” by Noralane M. Lindor et al appears in a special issue of Cancer Biomarkers and is available by subscription only. I'll try to get a reprint and post it to the geneforum resources. Unfortunately, I cannot even tell you which laboratory was found to be the "gold standard", but I will try to find out.

The tendency to believe the results of a single genetic test may result in part from our acceptance of technology we don't fully understand. We may also each have an inborn or learned tendency to accept a diagnosis, figuring that tests are generally accurate. How far we challenge a result, or how often we look for a second opinion, may be dictated by our personal feelings, our insurance coverage, and or general outlook on life.

I think what matters in this particular article, and the study on which it is based, is that testing can itself be tested. The lead author, Noralane M. Lindor states,

This experience flushed out some important principles in MSI testing…and demonstrated that a very high degree of concordance for MSI testing is feasible….We strongly urge all clinical and research laboratories conducting MSI to participate in a sample exchange validation with an experienced group or consortium and that clinical laboratory certifying bodies develop plans to evaluate quality of MSI testing results being returned to clinicians and patients.

We as consumers can encourage studies of this type and help make testing more reliable--even if we don't know all the intricate details involved in the testing and its interpretation.

Marie Godfrey, PhD

 

Does your physician know enough about genetics to help you understand the implications of genetic testing?

You probably only see your physician for short visits. It is unlikely that he or she will have time to explain the relationship of your genes to your health. Unfortunately, it is also unlikely that he or she knows enough about the genetic basis of disease to help you understand the details of particular diseases or conditions. A report from Case Western University presents this dilemma in an article, The Diagnostic Dilemma. They state the problem as follows:

Doctors will soon have an arsenal of new genetic tests to help select the appropriate treatment or drugs for patients. Will they know how to use them?

If you're lucky enough to have good health insurance--one that stresses preventive care--and you're interested in your genetic propensity for specific diseases or conditions, you will probably get more help from a physician's assistant. They often, in general, give you more time and are more recently connected to their formal schooling. However, a survey in late 2005 indicated that:

Allied health professionals are providing genetic-related services in clinical settings. However, sufficient instruction in genetic knowledge and skills is not being provided in their undergraduate and graduate training programs. (Assessment of Allied Health Graduate's Prepatation to Integrate Genetic Knowledge and Skills into Clinical Practice; J of Allied Health 2005;34(3):138-144.)

A better option would be a genetic counselor. Next difficult question--how do you find one? My first suggestion, as always, would be the Internet. Another option is your insurance company's help line. These are generally staffed by nurses or others specially trained to help you access information outside the physician's office.

Marie Godfrey, PhD

Genetic testing provides key to treatment

It's time to write positively about genetic testing!

While genetic testing available online may have many faults, well-controlled, clinically determined and supported genetic testing can have immeasurable benefits. A story in today's Chicago Tribune describes one such case.

Lilly Jaffe, 6, who was diagnosed with Type 1 diabetes when she was 1 month old, "now has the freedom to be a normal, active child. She can go to sleepovers or play dates without mom coming along to do blood sugar tests and operate her [insulin] pump. She can eat snacks without counting carbohydrates or testing her blood. The Jaffes don't even keep insulin in the house anymore."

Graeme Bell, a professor of medicine and human genetics at the University of Chicago, is the one who suggested that Lilly get tested for a genetic mutation first identified by a research team led by a British researcher, Dr. Andrew Hattersley of Peninsula Medical School in Exeter.

In a study published in the New England Journal of Medicine, Hattersley and colleagues showed that nearly half of patients diagnosed with diabetes before the age of 6 months have a mutation in one of two critical genes that work together to form a channel, or valve, that regulates the flow of potassium ions in and out of insulin-producing cells.

Normally, as glucose from food builds up in the bloodstream, the channel is cut off, causing potassium to accumulate in the cells. That, in turn, triggers the opening of another channel, for calcium. As calcium ions flow into the cells, they respond by secreting insulin.

The mutation - thought to affect as many as one newborn out of 200,000 - causes the potassium channel to remain open regardless of blood sugar. As a result, insulin secretion is drastically reduced, to undetectable levels in Lilly's case.

Hattersley showed that sulfonylurea drugs--currently used to treat only Type 2 diabetes--help close the potassium channel when needed, allowing cells to respond to glucose levels and make insulin.

Lilly is the fourth person to be treated this way in the U.S. and one of fewer than 100 in the world. But researchers suspect about 2,000 people in the U.S. have her kind of Type 1 diabetes and could benefit if diagnosed and treated early in life.

Now, let's put the pieces of this success together:

  • A researcher in England studies patients with diabetes diagnosed before 6 months of age and identifies a couple of "diabetes" genes
  • The molecular basis for the mutation is identified
  • A professor in Chicago, suggests treating patients with a particular genetic mutation, suggests treating the diabetes in a radically different way.
  • A genetic test is developed and a patient, on testing, is found to have the genetic mutation
  • The girl's physician, director of the Comprehensive Diabetes Center in Chicago, puts the girl in the hospital and begins giving her low doses of sulfonylurea while gradually reducing her insulin, adjusting the insulin level as successively larger doses of the oral drug take effect.
  • Within 5 days, Lilly has a new, less-encumbered life.

O.K., there is a down side. Very, very few people are affected by this particular mutation. And there are many, many mutations out there. But, as research progresses and connections are made between genetic information, disease, and treatment, similar successes will continue to happen.

You can access the complete article at http://www.kansascity.com/mld/kansascity/news/breaking_news/15525781.htm

Marie Godfrey, PhD

Having another person's DNA tested will be illegal in the UK

In the UK, it will be illegal starting Sept 1 to take a sample of someone's DNA and have it analysed without obtaining their consent. According the New Scientist, in an article discussing the new law:

The legislation allows for some exceptions. For example, if a couple have a child and then separate, and the man has parental rights, he is entitled to have the child's DNA analysed without getting consent from either the child or mother. He could submit the DNA along with his own for paternity testing.

The new law, part of the Human Tissue Act 2004, applies to employers who want to check up on their employees, insurance companies hoping to avoid insuring expensive enrollees, and publicity hunters who follow celebrities around hoping to get a DNA sample.

Helena Kennedy, chair of the Human Genetics Commission (HGC), which advises the UK government, stated:

Until now there was nothing to stop an unscrupulous journalist from secretly taking an everyday object used by a public figure - for example, a coffee mug - get a DNA sample from it, have it analysed and then publish their genetic information. DNA sequencing has impact not only on one person but on their whole family's privacy too.

To the best of my knowledge, there's no similar law in the US. This sounds like a good idea for American public policy, especially with the large number of ways available to have someone's DNA analyzed without them knowing. If you haven't read it yet you might be interested in Vern's story, a part of the new Consumer's Guide to Genetic Testing now being beta tested on this website. Check it out by clicking on guide in the text of the home page.

Marie Godfrey, PhD

If you choose not to have your newborn tested for genetic conditions, are you "endangering" your child?

As newborn genetic testing morphs into adding a newborn's DNA to a database, some prospective parents--and grandparents--are questioning whether the state should rule over testing and use of a baby's DNA.

The newborn testing--growing ever more popular and ever more intrusive--practiced in all 50 states is pretty much forced upon new parents. Often, the baby is taken out for testing--that familiar prick of a heel--before the mother has even had the opportunity to refuse. For those babies born at home, the testing typically comes at the first visit to a physician's office.

I was always in favor of this testing, especially for conditions that can be relatively easily treated, preventing long-term serious effects. This is the case for the condition known as PKU--phenylketoneuria--where the newborn's inability to digest certain proteins can result in irreversible brain damage. These older tests are generally for the accumulation of specific biochemicals in the blood, and are not DNA tests.

But, recently the Children's Hospital of Philadelphia (known as CHOP) announced that they will begin collecting, testing, and storing DNA from newborns--unless the parents opt out of the program. What do they intend to do with the DNA? As I heard it, they plan to build a DNA database they can screen for genes they can study and--perhaps--patent. As with all "great, new ideas", no end of benefits are promised us.

Meanwhile, parents in Nebraska were in court not long ago for refusing to permit blood testing on their newborn infant. Their reasons were religious: letting blood releases some of the body's life. Arguments in court suggested that these parents could be considered to be endangering their child, much in the same way a parent endangers a child who refuses treatment of an injury or immunization.

Changes in public policy all come about from people speaking up and expressing their own views. What do you think about these developments? What defines the line between endangerment, opportunity, and identity theft? Am I needlessly challenging a practice that's more beneficial than harmful?

Marie Godfrey, PhD

Is newborn genetic testing the same as DNA testing?

When hospital personnel take a small drop of blood from a newborn's heel, they are taking material for a genetic test. However, they are not going to analyze the DNA from that blood sample. The blood, trapped on a piece of filter paper, will be examined in a tandem mass spectormeter. This machine looks for specific chemicals within the blood, chemicals that accumulate if the newborn has certain genetic conditions, such as phenylketouria.

The number of tests now being conducted varies considerably across the country. I wrote some time ago about additional tests now required in Florida. Today's news was about Virginia. Seventeen disorders were added March 1 to the list of 11 disorders already screened for in newborns.

Most of the disorders are rare. Last year 129 children were found to have a genetic disorder. This year, the state expects to find an additional 46 cases, based on the increased number of disorders being tested.

Parents may refuse the testing for religious reasons.

According to the article in the Winchester Star,

With modern technology it’s possible to screen for hundreds of diseases. But it’s only helpful to screen for diseases that can be treated, said Dr. Bryan Kornreich, with Pediatric Associates of Winchester and chairman of WMC’s Pediatrics Department.

Dr. Kornreich was also quoted as stating:

Because screening tests are designed to catch anyone who could possibly have the disorder, they sometimes show false positive results, he added. More tests are required before an actual diagnosis is made. The testing is expensive and stressful for parents and child.

But, he recommends that additional testing not be done unless there's a family history of the disorder.

A national panel is suggesting that states broaden their newborn testing programs to include more of the disorders that can be treated with diet changes. These treatments can prevent brain damage. For more information on newborn testing, check with the March of Dimes or your pediatrician.

Marie Godfrey, PhD

What genetic tests are mandated for my newborn?

If you're wondering what tests are mandated and/or available in your state, you can review a comprehensive list updated late in December at http://genes-r-us.uthscsa.edu/nbsdisorders.pdf. Don't expect to understand what many of the names mean. To learn more about specific conditions, and what treatment offers, look at www.doh.state.fl.us/cms/nbscreen-disorder.html. This site, provided by the Florida Department of Health gives extensive details on the 34 conditions they will be testing for.

As is often the case, one of the best sources for information is Wikipedia (www.wikipedia.org)--an online wealth of information on many, many topics--in a number of different languages. Just search for "genetic testing".

Marie Godfrey, PhD

Is genetic discrimination an urban (suburban, exurban) myth?

As a genetic counselor specializing in hereditary cancer syndromes, hardly a day goes by without questions like:

  • "If this goes in my record, can I lose my health insurance and life insurance?"
  • "If I have a mutation, will my kids still be able to get health insurance?"
  • "If they know I have a higher risk for breast cancer, can they refuse to cover my treatment?"
  • "My PCP said that if I test positive, they could cancel my health insurance. Is that right?"

The answers are: no, yes, no, and no.

The legal protections:

The HIPAA (Health Insurance Portability and Accountability Act) law, passed in 1996, states that insurers may not view the results of a genetic test as a pre-existing condition.

This law also requires that health insurance coverage be portable from job to job. In other words, as long as the insured does not have a significant lapse in coverage, the new group insurer must provide comparable coverage, regardless of previous medical history.

Most states also have laws that prohibit discrimination by health insurers and employers based on genetic test results.

The practical reality:

My experience as a genetic counselor over the past 3 years leads me to believe that the fear of genetic discrimination is overblown, and may in itself do more harm than actions by insurance companies.

For some people, the result of a genetic test may prove life-saving. To explain that dramatic statement, allow me to provide some background.

About 10% of cancer is known to be hereditary: that is, caused by an inherited mutation in a single gene. For example, a woman who inherits a mutation in the BRCA1 or BRCA2 gene faces up to an 80% lifetime risk for breast cancer, and up to a 40% risk for ovarian cancer. (Compare that with the population risks of 10-12% lifetime risk for breast cancer, and less than 1% lifetime risk for ovarian cancer.)

Women with a family history of breast and/or ovarian cancer, especially pre-menopausal breast cancer, may be offered a blood test to detect mutations BRCA1 and BRCA2. In most cases, this test is only offered in the context of genetic counseling to insure informed consent and proper follow-up.

If a mutation is detected, increased surveillance and/or prevention options are recommended, based on the best currently available evidence from the medical literature and the patient'spersonal preferences.

Yes, some of those options are drastic. Because we still do not have effective screening for ovarian cancer, approximately 70% of ovarian tumors are not detected until after they have infiltrated the abdomen. The prognosis is often grim.

Therefore, the recommendation for a woman with an inherited mutation in BRCA1 or BRCA2 is to have preventive salpingo-oophorectomy (removal of ovaries and fallopian tubes) after she is finished with childbearing. Studies show that in 10- 15% of women with BRCA1 or BRCA2 mutations having this preventive surgery, occult ovarian cancer is already present.

Thus my daring statement about the possibility of this genetic test saving lives.

If such a woman refuses testing for fear of discrimination, where is the greatest possibility for harm?

In my experience, health insurers have become more and more willing to cover BRCA1/BRCA2 sequencing because they understand that it is solid preventive medicine. And they are much more willing to cover, for example, breast MRI's for women known to be at higher risk.

I welcome the opportunity to blog here, and welcome feedback. My hope is to help guide conversation about genetic testing and discrimination toward the realm of its practicality in the context of medical care, and away from fear, based on imaginative "what if's ....?"

Of course there are larger societal issues regarding insurance coverage and medical costs. I am saddened and ashamed that millions of Americans have no health insurance at all. For them, a $3000 genetic test is out of the question. Let's put those concerns in the political arena where they belong by electing legislators who will push for universal coverage.

And for the women who we know are facing an 80% risk for breast cancer, let's try and make sure they can get the best preventive care available to save their health and their lives.

Risks of online genetic testing

The Geneforum poll on DNA tests has been running for quite a while. Currently, we have votes from 300 people. Of these, 44% have purchased or would purchase a DNA test. A similar percentage (44%) selected one of the "negative" options. As we might expect, few people added a comment.

Whatever your answer was, you may be interested in the following article, posted today on the Hindu News Update Service. The article actually came from London's Guardian News Service. Naturally, I latched on to it, since I am quite leary of genetic testing available online. Here's some of what the author James Randerson said.

The genetic testing services available at present can't give you the power to make effective and ethical decisions about how such tests might impact your life- though they might aspire to, or insist they can.

As I described earlier in a blog entry, the reliability of four companies was tested by a US Government Accountability Office investigation released in July (http://tinyurl.com/gzxur). Fourteen "different" samples--which actually came from only two subjects--were sent to these companies and the results compared. TheGAO's damning report shows that the companies - which charged between $89 and $395 for the tests - provided inconsistent results and offered vague and misleading advice to their "clients".

The companies?

  • Suracell from Montclair, New Jersey
  • Sciona Inc of Boulder, Colorado
  • Genaissance Pharmaceuticals of Newton, Massachusetts
  • Genox and Genelex Corp of Seattle, Washington

Randerson's report goes on to describe pharmacogenetics--a field which is predicted to tailor treatment to a person's genetic makeup. I'll write more about that in the next entry.

To see all of Sanderson's article, go to http://www.hindu.com/thehindu/holnus/008200609070321.htm

Marie Godfrey, PhD

Should egg and sperm donors be genetically tested?

A flap in New Zealand over allowing gay men to be sperm donors has--naturally--raised many additional questions. I'm particularly interested in the genetic testing application.

If some people believe there's a gene for "gay", and insist that gay men be required to stipulate their gayness on sperm they donate to a sperm bank, should all donors be required to specify their genetic heritage? Is having a gene for a fatal disease worse than having a gene for being gay? What if an egg donor has the BRCA genes? Should that be disclosed?

Hmmmm. I've seen sperm donor catalogs, but haven't seen egg or embryo donor catalogs and don't know if they exist. But, arguing that a condition that could have a genetic component be disclosed in donating sperm, eggs, or embryos leads us down a terrible path toward eugenics. If that's a new word to you, check it out.

As always, your comments are welcome.

Marie Godfrey, PhD

 

Should genetic counselors be licensed?

Genetic counselors are currently licensed in Utah. Outside of Utah, genetic counselors practice without a license. Most are well-qualified and ethical health care professionals. Many are board-certified by the American College of Genetic Counseling, but certification and licensure are two different things.

There has been a push in the genetic counseling community in recent years to support licensure in other states, and eventually nationwide. As the availability of genetic testing increases, so does the risk of an unqualified (or underqualified) person hanging out their shingle, calling themselves a genetic counselor, and endangering the well-being of those who choose to pay them a visit. Licensure ensures that healthcare professionals are qualified to perform their jobs and defines their scope of practice. It also gives the public a course of action should they want to file a complaint.

Counselors in a number of states are in the process of drafting legislation to require the licensure of genetic counselors. Some state groups have gotten as far as a bill on the floor only to uncover unexpected opposition from other lobbying groups. Because these changes have to occur on a state-by-state basis, we are learning about the best approaches as well as the barriers as we go.

Doctors, nurses and other allied health professionals are licensed. Massage therapists are licensed. Hairstylists are licensed. Realtors are licensed. The list is long.

It makes sense to me that if the person cutting my hair needs a license, so should a genetic counselor. After all, hair grows back. The impact of genetic testing and diagnosis can change a person's life.

What do you think?

Nicole Teed, MS, CGC

Should I get my DNA scanned, even though it might reveal that I'm fated to suffer some incurable disease like Parkinson's?

The author of an article that appeared in Wired, at was asking a question many of us have asked:

Should I get my DNA scanned, even though it might reveal that I'm fated to suffer some incurable disease like Parkinson's?

The answer was, in the end:

So, no. Don't do it. Or at least use a lab your doctor recommends; don't search for one on Google. DNA tests are barely regulated, and plenty of online labs are fly-by-night "Canadian" Web pharmacies. And choose a lab that also offers genetic counseling, because you'll need someone to help decipher your results

The author suggested that people choose to pay for a genetic test because they think they're buying a "sense of control". If you know what your future might be, you can "prepare for it - or even prevent it". But, acknowledging that genetic results are "probabilities, not certainties" the author concludes that broad tests--or a number of tests--will turn up something. Do you think you'll have more control over your future if your test results says, "eat better, stop smoking, get more exercise"?

And, does learning you have one of the BRCA mutations mean you're going to choose a double mastectomy? That doesn't sound like control to me.

Well, maybe you are just curious. What will you do if you get bad results--do you tell your children, your relatives? Will you tell your insurance company? If you do, they may cancel your policy (even though it's supposed to be illegal); if you don't tell them, you're committing insurance fraud.

So, this article's author says: "Don't do it." I say, consider first what you will do with the results, then consider a genetic test--but be sure you choose one you can afford, both security-wise and money-wise. Better yet, consider putting it on your to-do list--for a year or two from now.

geneforum.

Marie Godfrey, PhD

What are the risks associated with genetic testing? It's not all about the numbers

For several years as a prenatal genetic counselor, I spent my days discussing pregnancy risks with expecting women and couples. One of the most common reaons for referral was a screen-positive result on maternal serum screening. (At the time, first-trimester screening was in its infancy, so I'm referring here to second trimester screening) This blood test is performed in the second trimester of pregnancy and outputs the risk for spina bifida, Down syndrome, and trisomy 18 based on three (or, now, four) maternal serum proteins.

It's intention is to flag those pregnancies that are at higher risk, so that further investigation with high-resolution ultrasound and/or amniocentesis can be offered. It's real effect is to scare the living daylights out or pregnant women, who often assume that their baby definitely has the condition instead of simply an increased risk for the condition.

Here is a common risk-communication scenario:

The results of the maternal serum screen indicate a 1 in 100 chance for the fetus to have Down syndrome. That's 1%. Or, turned around, there is a 99/100 chance or 99% chance that the fetus does NOT have Down syndrome.

However, to find out for certain, amniocentesis must be performed. There is a chance of pregnancy loss with amniocentesis that's usually quoted around 1 in 200, or 0.5%.

The risk of pregnancy loss is lower than the risk of Down syndrome. If you were making a decision based solely on the numbers, it makes sense to have the amniocentesis performed.

However, it should not surprise you that people making decisions about their pregnancy and future child aren't concerned only with the numbers. They are concerned about lots of other factors: facing the possibility of a child with disabilities, making a choice about abortion, miscarrying a healthy pregnancy, getting poked with a big needle. I think you get the picture.

Often, it boils down to what I like to call the "rock or a hard place" question. Would you feel worse if you delivered a child with Down syndrome and didn't have the diagnosis prenatally, or if you found out you experienced pregnancy loss because of amniocentesis?

Nobody wants to make that kind of decision, and nobody does it based just on the numbers. Throw in the complexity nature of families, reproduction, marital relationships, past experience with disability, and so many other factors, and you can understand why it's call genetic counseling.

Nicole Teed, MS, CGC

What can happen if a genetic test is wrong?

The Ohio Supreme Court in the US ruled this month (May 2006) that parents may sue on the basis of medical malpractice in the event of negligent genetic counselling or the negligent failure to diagnose a severe or fatal condition in the fetus that would have caused them to seek an abortion. This decision arose in response to the suit of a couple whose eight year-old son was born with trisomy 22, a genetic condition that means he is severely disabled. The results of genetic testing prior to conception showed a balanced translocation between two choromsomes (part of the DNA was switched, or transposed). When the woman became pregnant, she had a chorionic villus sampling (CVS) test. The test stated that the fetus was female and had the same translocation. Therefore, no ill effects were expected (the woman, after all, was not affected). Ultrasound tests showed normal development. Unfortunately, the newborn was male and severely disabled. The parents sued, claiming that the hospital had "negligently performed and interpreted the diagnostic tests and that they were negligent in their failure to recommend further tests that would have revealed Matthew's genetic abnormality" (see law report) with the result that they were denied the option to terminate the severely affected pregnancy. They claimed damages for the costs of pregnancy and delivery, of raising and supporting a disabled child, and for the emotional and physical suffering associated with having a severely disabled child. The court allowed the claim for 'wrongful birth' to stand, but ruled that only those costs associated with pregnancy and birth could be claimed for, overruling a lower court decision that the parents could sue for the additional costs of raising their disabled child over those for raising a normal child.

Courts in the US appear to be reluctant to grant claims by parents for the financial burden of caring for a severely disabled child where the cause of the disability is genetic in origin. However damages for ongoing care costs as part of a 'wrongful birth' suit have been awarded by a few US states where the disabling condition arose during delivery.

A negative result on a genetics test doesn't mean you're safe

Many of the online sites that offer genetic tests that tell you whether you may get cancer are not telling you the whole truth. With the news releases today and yesterday about a "new" genetic test for existing colon cancer, I started searching for similar items on the Internet and came across another one of those "recurring numbers".

This time the number is 5--5% of colon cancers may be associated with genetics. We already know that only 5% of breast cancers are associated with the BRCA1 and BRCA2 genes. Now, we have an additional group of very important cancers that do not appear to have a strong genetic component.

So, what do you do with the results of a genetic test you purchased online:

1. Recognize that the results refer to only 5% of the known associations between the cancer you're concerned about and genetics. The other 95% is not covered by the genetic test.

2. Remember that having one of the breast cancer genes or colon cancer genes does not mean you are destined to have that cancer. These genes (mutated genes, that is) are more likely to be found in those with breast or colon cancer than in the general population. People who have the gene--these are typically identified in family studies--do not necessarity have the cancer. Their chances are higher, but a lot more must be taken into account than the genetic mutation.

So, that genetic test you're interested in only "sees" specific genetic mutations and only 5% of breast or colon cancer is associated with these mutations.

Again, I caution: think about how you will deal with the results of a genetic test if you purchase one and send it in. If you get an answer that says you have the "bad" genes, will you have your breasts or colon removed? If you get an answer that says you do not have the "bad" genes, will you consider yourself safe and stop doing all those things doctors say help us avoid these cancers? Will you be devasted if you later discover you have one of these cancers?

Use the Internet to search for additional information on any test you are considering. Believe only reputable sites and, if you choose to have a test for breast cancer or colon cancer genes, understand the tests' limitations and use the test results as a part of your heath care--not all of it.

Marie Godfrey, PhD

Gender test questioned by more parents

The uproar about Acu-Gen’s Baby Gender Mentor continues. The test—advertised on the provider’s website as a “NEW Baby Gender Mentor Home DNA Gender Testing Kit”—is presumably based upon identifying a Y-chromosome in fetal-specific DNA obtained from a few dried drops of mother’s blood. If there’s a Y, the baby’s a boy; if there’s no Y, the baby’s a girl; if you’ve told them ahead of time you’re expecting twins, they can tell you whether you have one baby of each sex. The other possible options are not described in the publicity.

The provider claims 99.9% accuracy—comparing their test to their claim for 80% accuracy of sonograms—and guarantees a 200% refund [if you meet certain requirements]. Yes, I intended the print of that text to be smaller.

So, what’s the problem?  Increasing numbers of mothers are claiming that the test inaccurately predicted the gender of their infants—but not all these infants have been born yet, and the provider of the test states that ultrasound is not sufficiently accurate to challenge their test. So, no one knows whether any refunds have been made or whether any of the "errors" have had serious ramifications. 

According to the Science Magazine article that the provider claims provides the proof that the test works, “Food and Drug Administration approval is not needed as long as the blood sample goes to a lab and the test is sold as a service rather than as a kit. The provider’s website interchanges the words test and kit quite frequently; however, because the actual testing is not done by the person who supplies the blood (as for example with a pregnancy test kit or the at-home HIV-testing kit), the conclusion that this is a test, not a kit, is probably appropriate.

Meanwhile, a Canadian company has been offering a fetal DNA gender test for more than 2 years. Their marketing is low-key, however, and the test uses fresh blood from a woman 10 or more weeks pregnant—not the dried blood from a woman 5 or more weeks pregnant.  

If the only risk were incorrectly buying the “wrong” gender clothing, maybe we could just say, “buyer beware”. We can only pray that no one considers terminating a pregnancy based on this gender test. Meanwhile, according to National Public Radio a couple of months ago, "customers and scientists are raising questions about the accuracy of the widely publicized genetic test; customers have complained to the Federal Trade Commission, and at least one law enforcement agency is investigating a company that sells the test."

You can see the Science article at http://www.pregnancystore.com/images/Baby%20Gender/Science%20Magazine.pdf and listen to the NPR report at http://www.npr.org/templates/story/story.php?storyId=4952404.

Marie Godfrey, PhD

Blog Entry | Genetic testing

Here come the lawyers--Baby Gender Mentor

I worked for pharmaceutical companies for many years and was always focused on patient safety. One indication I now use that a product is in trouble is when I start seeing law-firm ads on the t.v. In this case, the product is Baby Gendor Mentor--described earlier in this Genetizen blog.

The test is sold through ads in pregnancy and baby magazines and over the Internet and is supposed to tell an expectant mother the gender of her developing child as early as 5 weeks. The mother supplies a few drops of blood and the test says, congratulations you are expecting a ......!

Last fall, there were news items that the results were being questioned by a number of people. Recently, questions related to the test have again arisen. News programs that earlier contacted BABY Gender Mentor and Accu-Gen, the source of the test, were told to wait until babies had been born and see whether the test or a conflicting ultrasound was right in each case. The company claims 99.9% accuracy, but refuses to release any data. Now, some of those babies have been born. Again, though, there's no unbiased collection of wrong vs. right predictions.

What we have learned, is that a lawsuit has been filed by some mothers in New Jersey--the number of plaintiffs varies depending on the source you read. Here's the webpage for the lawsuit: http://www.babygenderinvestigation.com/ . As with any group seeking validation, the group is looking for people to add to the list of disgruntled purchasers.

Both ABC (http://www.abcactionnews.com/stories/2006/02/060220babyfolo.shtml)  and NPR (http://www.npr.org/templates/story/story.php?storyId=5235003) have recently aired reports. A website called in-gender.org (http://www.in-gender.com/cs/blogs/gender_selection_news/archive/2006/2/17/6646.aspx) has been following this and other gender identification issues for some time.

I'm sure there's more to come.

Marie Godfrey, PhD

 

 

 

 

 

 

Not related to Genghis Khan after all

When PBS television showed stories of famous people and their ancestry based on genetic testing, no one on the show ever asked, "How sure are you the results are accurate?" I remember wondering about that when a person who had always considered himself African American found little genetic connection to that ancestry.

Today, we learn that the University of Miami professor who was in the news because Bryan Sykes [of Oxford Ancestors] informed him he was a descendant of Genghis Khan, may not be able to claim that connection after all. According to today's Miami Herald, "Robinson helped debunk the link himself. In preparation for an appearance in a documentary that would have taken him to Mongolia, he asked Greenspan [of Family Tree DNA] to re-examine a DNA sample he had submitted to that firm in 2003."

The author of the Herald article was unable to contact Sykes, but offered the following reasoning for the different results:

Sykes' . . . testing revealed a link -- seven of nine genetic markers -- between Robinson's genes and a genetic signature that has been commonly associated with Genghis Khan.

Further testing revealed that markers not tested by Sykes put Robinson's ancestors on a different ''sub-branch of the Y chromosome DNA tree of mankind,'' . . . Greenspan said Sykes' initial results did not provide enough information to make a claim to Khan's genes.

The different results found by different companies reflects a variety of factors and doesn't necessarily reflect on the quality of genetic testing conducted by either Oxford Ancestors or Family Tree DNA. However, the failure to substantiate the initial results--do we even now know which results are correct?--has, in this case, resulted in some disappointment and a lost trip to Mongolia. And this testing was "identity" testing, believed to be far more accurate than testing for active genes.

I wonder how Robinson would feel if a body part had been removed, not just an ancestor.

Marie Godfrey, PhD

 

 

 

Testing misses some breast cancer-related mutations

An article appearing in newspapers around the world refers to a recent study published this week in the Journal of the American Medical Association (JAMA 2006;295:1379-1388). The following is a direct quote of the version written for Reuters Health, by Karla Gale:  

Commercial genetic testing does not detect all cancer-associated inherited mutations in women with a severe family history of breast or ovarian cancer. . .

"Women who were familial breast cancer patients were being commercially tested for inherited mutations in BRCA1 and BRCA2, and a very large number had reports returned that said they had negative results," Dr. Mary-Claire King said in a presentation Tuesday at a press briefing coinciding with publication of the Journal's theme issue for March 22/29 devoted to women's health.

Dr. King noted that it has been clear since BRCA1 mutations were first reported "that there were mutations that in principle could not be detected by conventional sequencing methods, no matter how perfectly they were carried out."

In the US, nearly all genetic testing of BRCA1 and BRCA2 is carried out by one company. Most of the mutations it can detect are small deletions or duplications.

Dr. King, from the University of Washington in Seattle, and her research team set out to quantify how many mutations would be missed by commercial tests. That's important, she added, because "risk reduction interventions for those with mutations are highly effective, but they are also horrifically invasive, including prophylactic salpingo-oophorectomy and mastectomy that one would not undertake unless she was at extremely high risk."

Their study included 300 patients with breast or ovarian cancer and at least three affected family members, for whom commercial testing yielded negative results.

The researchers used multiplex ligation-dependent probe amplification [MLPA], and other DNA- and RNA-based methods to detect genomic rearrangements in BRCA1 and BRCA2 as well as germline mutations in CHEK2, TP53, and PTEN.

They found that 35 (12%) of subjects had genomic rearrangements of BRCA1 or BRCA2. The reason they couldn't be detected by the commercial method, Dr. King explained, is that "they were genomic deletions or duplications that are much larger than can be detected by conventional sequencing, ranging from 1000 to 170,000 base pairs, incorporating part of BRCA1 or BRCA2."

Another 14 (5%) had mutations in CHEK2, which confers a doubled risk of breast cancer but no elevation in risk of ovarian cancer. Three (1%) had TP53 mutations, which confer a 90% risk of developing one of the cancers associated with the Li-Fraumeni syndrome.

All the mutations they found were individually rare, the researcher noted.

Many of the other subjects may also be carrying cancer mutation genes that have not yet been recognized, Dr. King told Reuters Health. "We are continuing to look for additional breast cancer genes that will explain inherited breast cancer in those patients."

Meanwhile, a partial solution to improving genetic testing, she added, would be "an open, competitive marketplace for development of genetic testing for BRCA1 and BRCA2, just as we have for most other genes."

That includes "nonexclusive licensing of patents on genes, because competition is the best way to improve technology and bring the price down." As opposed to drugs for which patents make sense, she added, genetic tests are much cheaper and take less time to develop, and they are not subject to FDA approval.

Breast cancer can be expected to hit one woman in eight during her lifetime. Testing promoted as a predictor for breast cancer, and controlled primarily by one company, only looks for mutations in BRCA1 and BRCA2, and these genes are associated with only 5% of breast cancers. Now, we also know that there are mutations that are not being detected even by this test. So, genetic testing even for breast cancer--the most widely touted of tests available for potential disease--has a long way to go.

Marie Godfrey, PhD

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What do I need to know about that $99 Home DNA kit?

Wait! Don't run right out and buy the $99 DNA testing kit described in your Sunday newspaper! Check it out and see what's really involved.

Here's what the blurb in your newspaper says:

Genetics has moved from the lab to the supermarket. Lund Food Holdings, a grocery store company, has started selling home DNA kits developed by Sciona Inc. within its pharmacies and at sciona.com. Purchasers can test their genetic predisposition for disease in five areas: bone health, heart health, inflammation, insulin resistance and how well the body rids itself of toxins. "This is a way of finding out if you're susceptible to illness before symptoms appear," says Yael Joffe, a Sciona dietitian. Consumers use a cheek swab to take a DNA sample, which is mailed to a lab. Within three weeks they will receive a detailed report that reviews the findings and offers nutritional steps to improve their health.

I went to the website for Sciona, Inc. and found a little bit different picture.

First, the cheapest test there is $126 (which apparently includes shipping).

Second, there's not one test, but 5 individual tests and one comprehensive (all 5) test ($252).

Third, the disclaimer at the bottom of the page says:

The Cellf Genetic Assessment is not a genetic test for disease or pre-disposition to disease, nor does it determine a medical condition. The information that will be provided is not a diagnosis of a medical condition. Individuals with specific concerns about their health status or genetic testing should consult their doctor or genetics professional.

Fourth, by clicking on Product Specifications, you can see what genes the tests claim to look at. You may find a bit of overlap. I wondered what "genetic variation screened for variations found in your gene" meant.

Fifth, I found the following of particular interest:

Sciona's Genostics Rules Engineâ„¢ is proprietary, patent-pending software based on a data mine of over 1,000 scientific studies. The software uses complex mathematical algorithms to produce personalized health intervention recommendations based on genetic profile, diet and lifestyle. We have 10,000 genes in our library, and actively track approximately 200 genes that may have a strong nutritional intervention link. We are concerned only with genes that may indicate a potential risk for a health condition that may be manageable through changes in diet, lifestyle and/or nutritional supplementation.

Not long ago, in a similar Sunday newspaper, I read an article by someone who submitted a DNA sample for a similar test (may have even been this one, but I don't have the article handy). His final response was something like this: for the same amount of money, I can read nearly any article on health and diet and learn the same things. I don't really think I needed to pay this amount to learn that I need to eat more fiber and excercise more often.

Personally, I'm not willing to pay the money to have a computer plug my name into 30 pages of "you should" information--regardless of my genetic background.

Marie Godfrey, PhD

Investigation finds that home DNA testing kits promise more than they can deliver

Several newspapers lately have reported on the General Accountability Office's testing of genetic tests sold online. According to the U.S. News and WorldReport, "these 'direct-to-consumer' genetic tests, which cost from less than $100 to over $1,000, have proliferated on the Internet in recent years, many promising to give consumers genetically based nutritional advice or advance warning of life-threatening illnesses."

Unfortunately, the GAO report concludes that the tests make predictions that are medically unproven and "so ambiguous that they do not provide meaningful information."

According to news reports, "the GAO investigators took two DNA samples via cheek swab, one from a 48-year-old GAO employee and one from the 9-month-old daughter of Gregory Kutz, the GAO's managing director of forensic audits and special investigation, and submitted the two samples under 14 phony names. The online firms reported back that the 14 fictitious customers were at risk for a wide-ranging list of serious diseases, including cancer, diabetes, and high blood pressure--despite the fact that only two people were tested."

The Senate Select Committee on Aging held a hearing on the GAO's findings last week. Genetic science holds great promise," said Republican Sen. Gordon Smith of Oregon, chairman of the committee, who requested the GAO investigation. "Clearly, consumers are being misled and exploited by this modern-day snake oil, and I am shocked to learn how little the federal government is doing to help consumers make informed decisions about the legitimacy of these tests."

The Federal Trade Commission is also urging consumers to be cautious about over-the-counter genetic tests, noting that companies may post your results online, which could raise privacy concerns. A new brochure offers tips and advice on these new at-home tests.

Many of your questions can be answered here, right on the Geneforum website. Check out the new Consumer's Guide to Genetic Testing.

Marie Godfrey, PhD

What do you think a DNA test will tell you?

For one to several hundred dollars, you can have a DNA test done. Before you order that test, ask one simple question: what will you do with the results? Even more pertinent may be: what will the company do with the results?

The New York Times on Sunday presented the story of Georgia Kinney Bopp--a genealogist with a mission. Should you happen to run into her, keep your mouth closed--literally. Ms. Bopp travels with a DNA kit and can be very persuasive. Ms. Bopp apparently cornered a second cousin in Reno, Nevada, pulled out a DNA kit, and convinced him to give her a sample.

To me, the interesting part of the story was the description of how limited the information is that Ms. Bopp gets when she gets results from a DNA test. According to the article,

DNA tests can deliver surprises. In some families, someone may discover, for example, that he or she lacks a DNA connection to their supposed blood relatives.

What would you do if you learned from a test that your mother was not your mother, or your grandfather was not your father's father? It happens. Is it accurate?

One DNA test will not be enough for much family history testing--even for a paternity test you need samples from both the supposed father and the child. So, if you're searching for your ancestors, prepare to pay for more than one test.

The article goes on to state:

The  DNA tests have limitatiions, showing only small slices of genetic history. Here is why: a popular test, the Y-DNA, analyzes the chromosome that is passed virtually unchanged for generations from father to son. . . .Another test looks at mitochondrial DNA, a form that is passed from a mother to all her children. Both men and women can take the test.

The Y chromosome test tells you about only one male ancester in a generation, and the mitochondrial test tells you about only one female ancestor. . . .It doesn't take into account the fact that if you go back just 10 generations (300 years), you have 1,024 ancestors in that generation. Just seeing one ancestor, means you're looking at a very small slice.

Now, what does the company do with your DNA and/or the results of your test? If the results are fully anonymous, how do they send you the results? Will they add your DNA results to their database so others can check their DNA against yours? Did you hear about  the adolescent who found his "anonymous" sperm donor through DNA database information on the Internet? 

Have you ever wondered: How many kinds of DNA tests are there? Will you be able to understand the test results when you get them? What does 99% exclusion, 75% inclusion mean? If you "relate" to a tribe now living in Africa, does that mean your ancestors came from Africa? If you're black, but your DNA is 79% European and 21% Asian, are you still black?

None of these questions address the more dangerous side of DNA testing--the medical side. If you have a test for a "breast cancer gene" and the test result says you have a 50% chance of developing breast cancer, do you schedule a double mastectomy? Will your insurance pay for it? What will you tell your sister or your daughter about their chances of developing breast cancer?

Please don't  blindly order a DNA test and send your personal genetic code off to some company you've only read about through an advertisement. Check into things first. It's too late once the results arrive.

Marie Godfrey, PhD

 

What impact will DNA testing have on your life?

Some people expect that when they send a cheek swab off for DNA analysis, the results they get will be the final answer to a specific question: will I get cancer, who were my ancestors, is this man the father of my child?

Let's assume for the moment that the tests have no false positives, false negatives, or technical complications that put the data in question. The results come in and you have an "answer". Did you think ahead of time about what the answer will mean to your life?

If you considered the answer to be a part of a much larger whole, that must fit together and be rational, then you are more likely to be satisfied with the answer you received and behave in a reasonable way.

I received in my Google alerts today an article from the Hartford Courant, my hometown newspaper. It was called, The DNA Path To Identity, and was written by Frank Harris III. As you could see from his photo Mr. Harris is black. What you can't see is what his DNA test told him, in his words:

In my case, my DNA markers matched definitively with those of the Ibo people in Nigeria and the Kimbundu people, also known as Mbundu, in Angola.

Mr. Harris approached his DNA test with an open mind and a clear intent to select as accurate a test as possible. He chose a company that focused on African Americans and investigated the company, its capabilities, and its do-director. After paying his money and receiving his test kit, Mr. Harris sent it and and received results:

The results were contained in a brownish folder that opened up to reveal the words "African Ancestry" in a pyramid. There was a cover letter from company president Paige. It said: "It is with pleasure that I report that our PatriClan analysis successfully identified your paternal genetic ancestry. The Y chromosome DNA sequence that we determined from your sample shares ancestry with the Ibo people in Nigeria and the Kimbundu people in Angola."

There followed specific scientific data related to polymorphisms, which are different forms of DNA. Along with the packet of information was a copy of my Y chromosome polymorphisms, a certificate of ancestry authenticating that my polymorphisms matched with the two groups of people. There was also a full-color map that illustrated my ancestral origins, along with an "African Ancestry Guide to West and Central Africa" that describes the countries and the people. I had expected to have just one country and one people, but was told that "while the groups differ socially and culturally there are people within them who share a common genetic ancestry."

Now, how does he fit these results into his life?

All of this leads to more questions about identity. Instead of being a black- or African-American, am I now a Nigerian-American or an Angolan-American? Or am I, more accurately, a Nigerian-Angolan-American? These questions stem just from having my paternal lineage checked. What would my maternal lineage reveal? Should I acquire this knowledge and what it reveals, there will still remain much I do not know.

So, he continues the other ways in which he is tracing his heritage, because:

Any knowledge of my family tree pertaining to nation of origin and ethnicity is incomplete without names, dates and specific places.

Mr. Harris, I think, is different from many parents. Rather than fighting the teachers who assigned the "find your heritage" projects for his daughters, he thought of creative ways to help them and--even though the results of his DNA test did not form part of his younger daughter's project, she did well. He comments on the teachers this way:

And as to these projects that spark such uncomfortable feelings, I don't fault the teachers for assigning them. Knowing one's origins can instill pride and be an important way to study history and learn respect for other cultures, as well as one's own. But in this quest for identity and affirmation that all groups have, it is important to recognize that finding the country of one's origins is still a particularly arduous task for blacks.

It is also important for teachers to recognize this as a rich teaching opportunity to show the similarities and differences between students. It is an opportunity to shed light on the larger role that slavery and race have played in shaping American history and cutting off the lights to a specific African connection - not only for blacks with deep American roots, but also blacks with roots in the Caribbean who would face similar challenges if asked to name the country in Africa that they were from and the ethnic people from whom they are descended.

In commenting on the man from the PBS African-American series, he writes:

I was skeptical about those results, since this man looked more black - albeit light-skinned - than white or Asian. But I knew that DNA analysis has shown that all humans have more in common in our biological composition on the inside than the physical differences on the outside. I also knew race was a sociological definition more than a biological one. In addition, I knew years ago geneticists had traced the first original human species on Earth to a woman in Africa.

You can read the full article at http://www.courant.com/news/local/northeast/hc-dna0219.artfeb19,0,1387989.story?page=3&track=mostemailedlink

Marie Godfrey, PhD



What is maternity testing?

We've frequently heard of paternity testing--determining if a specific person is the father of a child. Generally, this type of test is used to establish paternity for child-support payments.

But, how often do we hear of maternity testing? While I was checking on a story my daughter told me about a woman whose biological children matched each other more than they matched her (on DNA testing), I happened on an ad from a company touting maternity testing.

As the company website explains,

The DNA maternity test is useful for individuals who need to determine maternity in a vast number of situations. The most common situations that we see at our laboratory are as follows:

1. IVF: The DNA maternity test is often ordered by mothers who have had a child through in vitro fertilization to ensure that the IVF laboratory had used the correct embryo for implantation.

2. Adoption Reunification: Adult children who were put up for adoption often search for their biological mothers. Once found, most reunified mother child pairs choose to conduct a DNA maternity test to ensure that the correct mother and child have been reunified.

3. Hospital mix ups: After birth, babies often all look very similar. Our laboratory frequently experience situations where hospital staff believe that they may have mixed up the tags on the babies and either the hospital or the children's mother proceed with DNA maternity testing to ensure that a hospital mix up had not occurred.

They go on to describe the difference between a "legal" and a "just-for-information" test:

You have two choices for DNA maternity testing: legal and private. If you require the results of the DNA maternity test for use in court, you must attend an appointment for chain of custody sample collection to ensure court admissibility. However, if you require the results of the test for your own knowledge or to help you to decide what step to take next, the private home DNA maternity test would be the best choice for you because it is fast, discreet, and just as accurate as the legal test.

Hmmmm, now we finally get into the piece I was interested in in the first place: accuracy and reliability. To support their assertion that the test "will conclusively determine whether an alleged mother is the true biological mother of a child", they state:

Our testing laboratory is accredited by both the International Standards Organization (ISO) and the American Association of Blood Banks (AABB). These accreditations provide full guarantee of accurate, straightforward, and reliable results.

ISO is the documentation of practices performed in a business and has to do with management documenting what they do and doing what they document. It is not necessarily a guarantee of accuracy or reliability. The AABB provides standards for the testing and handling of blood, not specifically for DNA testing. It is interesting to me that their list of AABB Accredited Parentage Testing Facilities, updated December 20, 2005, does not include the company offering the maternity test.

So, if you have $260 and want to determine whether X is the mother of Y, you can get one of these tests. I've intentionally not included the company name here, because I'm not into advertising. Also, I've been reading a book lately on the validity of DNA testing--note that I said validity, not accuracy or reliability--and I'm not as gullible as I used to be. More on the statistics of test results in another blog. Meanwhile, I'm still looking for the news story I went after in the first place.

Marie Godfrey, PhD

What is the cost of genetic testing?

Would you ever consider ordering something online that you don't know the cost of? Apparently the laboratory that controls the market for BRCA (breast cancer) genetic testing expects potential customers to do just that.

If you go to Myriad's website and click on the button for ordering a genetic test for BRCA1 or BRCA2, or both, you'll fill out a form asking for information on one or more of the tests available. No cost is indicated; the site doesn't even say, "information is free; you won't be charged until you request an actual test". If you go to the page on reimbursement, you'll find a statement that the average person who uses insurance coverage can expect to pay $300.

Ummm, according to the articles I've read on cost, there may be a zero missing from that number--particularly if you have no insurance or choose not to use it. Tests can be as low as $300, but could also be as high as $3000. The formal "test request form" you send in with your blood sample asks for credit card and/or insurance information, but again, no numbers are given. The information page on reimbursement adds the following warning:

Canceling the Test
If you cancel a test within 48 hours of the blood draw, you will not be charged. However, after 48 hours, you are responsible for payment, even if you decide not to receive test results.

Sounds to me as though you really need to have your ducks in order before you "decide to have a test". Of course, you can use the 800-number; perhaps you'll reach a person who knows and will tell you how much the test costs.

Marie Godfrey, PhD

Blog Entry | Genetic testing

Gene tests a waste of money

The following information comes from Ian Sample, a science correspondent for The Guardian, a British newspaper. To read the full article, go to http://www.guardian.co.uk/science/story/0,,1697962,00.html

The Natiional Health Service has a number of single-gene tests available. These tests, look for mutations know to be associated with specific diseases such as cystic fibrosis. The new tests--described by Sample--claim to measure a person's susceptibility to diseases such as cancer and Alzheimers. Sample quotes Zimmern and Khoury, who participated in recent meetings discussing genetic testing:

"Even if there's theoretical evidence the genes are linked to a disease, that's often far too little to go on. There's not one shred of evidence that these tests benefit human health," said Ron Zimmern, director of the public health genetics unit at Cambridge University.

Muin Khoury, director of genomics and disease prevention at the prestigious Centres for Disease Control and Prevention in Atlanta, told the meeting: "There are more than 1,000 genetic tests on the market now, with many available over the internet, but suffice it to say we have no idea whether they are of any value." In many cases, a person's family history was a better indicator of future disease, he said.

Genewatch, a lobby group that watches over announcements related to genetics, is preparing a report on 11 genetic tests that claim to help a person tailor diet to genetic test results. And scientists in the Iceland group recently announced plans to develop a test for a gene reportedly linked to  type II diabetes. In response, Sample quotes his two sources:

 Even if such a test is made available, the advice to those testing positive will be the same as that given to all - eat sensibly and take more exercise, said Dr Khoury. "If that's the case, why buy a test?"

"What line should society take?" asked Dr Zimmern. "Should it say that if it doesn't harm you, you can allow the snakeoil salesmen? Or does society have an obligation to make sure the consumer is only buying tests that work? I think industry has to get together with government to set up studies to test whether these tests make any difference to people's health."

Members of a Capstone class at Portland State University assisted by geneforum are reviewing websites as part of their efforts to produce a "Consumer's Guide to Genetic Testing". If you have a site you'd like them to investigate or a question you'd like to ask, let me know.

Marie Godfrey, PhD

 

What should primary care physicians keep in mind about genetic testing?

Genetic testing has made the world of the family physician much more complicated and controversial. You should expect greater demands from your patients for genetic testing, especially as more tests for diseases become available through the mail or Internet.

As the primary care provider (and if genetic counselors and medical geneticists are not readily available), you and your patient(s) should go though an information gathering phase. This will help you and your patient ascertain whether genetic testing is necessary and/or advisable. In addition, when genetic counselors or medical geneticists are consulted, the information you have collected from your patient will be very important.

Below are some general things to keep in mind:

  • Genetic testing is complex, and communication of risks and uncertainties must be attended to thoughtfully and critically. Consumers and healthcare professionals need to know that genetic information can have profound side effects i.e., possible insurance consequences, work discrimination, psychological side effects such as people’s perceptions of their body, family, and future. (from GDP transcript)
  • Genetic tests are quite variable. Some tests are quite clear cut and predictive and other aren’t at all. (GDP)
  • Genetic tests provide information about family members and relatives. Disclosure of family information can often be helpful to family members but also can lead to breaches of confidentiality that must be considered and addressed proactively. Health care professionals have a duty to warn. In other words, privacy regulations underscore the provider’s obligation to maintain the confidentiality of medical information. However, if the information represents a significant, imminent and remediable threat to another person’s health, the provider may need to consider whether s/he has a duty to contact the person (or in the case of a minor, the minor’s guardian or legal representative, in the absence of explicit permission.
  • Health care providers need to provide opportunities for their patients to express their reasoning and associated emotions in regards to testing. The most important goals of the counseling discussion is to ensure that patients have considered all aspects of the testing opportunity to his/her satisfaction in making this decision.
  • All diagnoses carry with them other social, cultural and psychological meanings as filtered through the patient’s viewpoint and health model. The physician must simultaneously assess the medical information to be conveyed, the patient’s baseline perspective and comprehension of the new information, the psychosocial implications of the diagnosis for the patient, and the support systems the patient has. A strong-patient doctor relationship can help the patient gain a perspective on his/her disease.

Urban legends and genetic testing

I heard a news item on the Today show, which suggested that a group of workers are being forced to take a DNA test so that a prankster at a hotel can be identified. After trying to track this down, I suspect it is another of the urban legends related to human body products and food contamination. Odd that it would be aired on Today--and not findable in searches of the MSNBC website.

This--and an e-mail I received on ovarian cancer--sent me to a website I had not explored before. This site, and a number of others apparently, tracks stories known as urban legends. these stories are intended to evoke emotion and they generate their own following, when the stories are passed along from one person to another.

I searched the site (http://www.snopes.com/) for genetic testing, genetic, and DNA and found a surprisingly low number of items. The only one of interest to human genetic testing relates to paternity testing. Recently, some newspapers suggested that as many as 30% of all fathers are raising children not their own. This urban legend is somewhat tricky because it involves statistics--that stuff so many of us don't understand.

First, the real percentage is closer to 1%--not 30%, so don't run out and get a DNA test for your children and yourself. Second, the fallacy of the numbers lies in the same selective population used in forensic testing. When the only people tested are those under "suspicion", the numerical "proof" of paternity or guilt is much greater than when the general population is tested. If 2 or 3 people are tested, and there's a DNA match between the children (or the victim) and one of the two or three people, this is often considered proof. If 1 million people were tested, the proof would be less sure.

So, don't believe everything you hear or read. It may be an urban legend, in which case you can check Internet sites to see if it turns up. Or, it may be that only a few people were tested. Or--it could be true! Whatever the situation, have fun with the story, but investigate deeper before you make any life-changing decisions. 

 Marie Godfrey, PhD

What's the difference between DNA profiling and genetic testing?

DNA profiling looks at repeated nucleotide sequences within inactive genes. Examining as few as 16 different locations in human DNA can yield very clear information on whether or not a DNA sample belongs to person A. This is how DNA analysis is used in forensic profiling. This is also what is now commonly referred to as a "DNA fingerprint". By the way, the techniques have changed in the past 10 years or so, so results from 10 years ago may not be comparable with results of today's analyses.

Paternity testing done by profiling requires samples of the purported father and the "child" (that is, the presumed offspring). The mother's DNA is not necessary, but can be helpful. In this case, a sample from each person can be profiled and the profiles compared visually or electronically. Alternatively, the samples can be tagged with two different fluorescent markers, mixed and analyzed--looking for similarities and differences. Lineage testing (maternal, paternal, ethnic) uses the latter technique, which is more prone to error.

Genetic testing for particular gene sequences (active DNA, for example, a particular cancer gene) can be done with DNA directly or by examining DNA's "expression"--messenger RNA. Here, the techniques are much more complex and subject to error and variations in interpretation.

Then we get to the most complex and weakest aspect of genetic testing--inferring phenotype (appearance, function, likelihood of disease, etc.) from genotype. Here, there may be lots of literature and hype, but little clear connection between a test and the prediction of a person's future. Even "known" genes may have many variants and results without supportive genetic counseling can cause more harm than good. 

Marie Godfrey, PhD 

 

Who regulates the quality of genetic tests?

I attended two excellent teleconferences sponsored by the Genetic Alliance.

One gave information on CLIA (Clinical Laboratories Improvement Amendment) and CLIAC (the committee who provides recommendations) and the move to implement a genetic testing speciality within its regulation. CLIAC recently gave notice that it will be proposing standards for genetic testing under the CLIA law. CLIAC reviewed all the comments it received on the public notice and is currently formulating a proposed rule to be released for comment at the end of this year or early next year. Learn more about CLIA and about CLIAC.

One of the things explained during the conference was why standards take so long to develop and implement. Rules--the word is a formal one--are the standards that tell how a law will be implemented. For example, the Clean Air Act regulates activities of manufacturers, cities, etc. through a series of rules. The rule proposed through CLIAC (as part of the Centers for Disease Control and the Department of Health and Human Services) will describe how genetics laboratories offering services to the public must function. You probably don't know it, but everytime a physician sends out a sample of your blood for testing, it must go to a CLIA-certified labroatory. So, physicians who send out samples for genetic testing to a CLIA-certified lab are just following the existing general rules about clinical tests. CLIAC's intent is to identify the specific needs of genetic testing that are different from other clinical laboratory testing and functioning.

The ones who don't have to follow the CLIA rules are the ones who receive test requests over the Internet or by phone directly from consumers. If you check the sites advertised along the side of your screen when you check out genetic testing laboratories, you'll find plenty who do not list CLIA certification as one of their qualifications.

The second teleconference I attended discussed information on CETT--the Collaboration, Education, and Test Translation Program from the Office of Rare Diseases (ORD). In May of 2004 this group met for the first time to discuss quality testing for rare genetic diseases. they met last in September 2005 and are currently accepting applications for new genetic tests. Their objectives are to foster the development of new genetic tests, help groups translate tests from research to clinical practice, and educate the public about rare genetic diseases. The special feature of this group is the strong sense of collaboration among clinical laboratories, researchers, and patient advocacy groups. You can learn more about CETT at http://www.cettprogram.org.

The Genetic Alliance helps patient advocacy groups with all aspects of their work, including working with patients, with media, education, obtaining and dispensing funding, and many other opportunities. They are very involved in public policy, as is geneforum, the group sponsoring this website and blog.

Marie Godfrey, PhD

 

Genetic testing regulations needed

I have been working lately with the Genetic Alliance to formulate priorities for their action. The group serves as advocates for patients with a wide variety of genetic conditions. As part of their work, the Genetic Alliance recently sent the following letter:

Letter to CMS Administrator Mark McClellan regarding genetic testing quality

February 28, 2006

Dear Dr. McClellan:

On behalf of the Genetic Alliance board of directors, I am writing to urge you to issue proposed regulations for a genetic testing specialty under the Clinical Laboratory Improvement Amendments (CLIA) of 1988.

As knowledge of genetics continues to grow and the number of genetic tests made available to consumers increases, the U.S. government has an obligation to maintain a regulatory framework that ensures the safety and utility of the tests being conducted without limiting the accessibility of those tests.  To this end, in 2000 the Centers for Disease Control and Prevention (CDC) issued a Notice of Intent indicating that the Centers for Medicare and Medicaid Services (CMS) would be issuing a proposed rule based on stakeholders’ comments received and elucidated by the CDC.  More than five years later, no such rule has been issued, and the genetic testing specialty that was recommended has not been established. 

The Genetic Alliance board of directors believes that the establishment of a genetic testing specialty under CLIA is a necessary first step toward a regulatory system that encourages new technology and ensures safety and accuracy when those technologies are implemented.  Since the CDC issued its Notice of Intent more than five years ago, the number of genetic tests available has increased substantially.  Today, there are more than 900 diseases for which genetic tests are clinically available, several hundred used in research, and even more in various stages of development.  Without a genetic testing specialty, CLIA cannot adequately ensure that consumers receive genetic testing services that are safe, accurate, and clinically useful.

I urge CMS to act quickly by issuing proposed regulations for a genetic testing specialty under CLIA.  I welcome the opportunity to meet with you and discuss these issues in further detail.

Sincerely,
Sharon F. Terry, M.A.
President and CEO

 There are two key aspects to testing quality: 1) performing the tests accurately and within established regulations and 2) having tests that actually test what they say they're testing. The first aspect is addressed by the letter above. The second aspect, developing and making tests available for both rare and common genetic conditions, is also an Alliance focus.

If you're interested in the activities of the Genetic Alliance, check out their website at: http://www.geneticalliance.org/.  

Marie Godfrey, PhD 

Who has oversight of genetic testing?

You may be surprised to learn that the government agency most responsible for "regulating" genetic testing is the FTC--the Federal Trade Commission. This group regulates advertising. If a company claims to do something they do not do, the FTC can intervene. However, the FTC has little control over the Internet and--contrary to its normal influence on other advertising--does not link with the FDA (Food and Drug Administration) to require that advertisers send out "Dear Doctor letters" to correct false advertising that appears on television or in print.

What controls are there?

The FDA, which oversees prescription and generic drugs as well as foods, does not review and approve genetic tests unless they are true medical devices--something that either must be provided by a physician (such as a heart pump) or directly diagnoses a condition (such as home HIV testing). The FDA considers most genetic testing "home brew". The FDA's extent of involvement then becomes the same as its involvement in any food or drug--no applications and approvals, but the FDA can insist that a product be removed from store shelves (e.g., ephedra) if it is shown to potentially cause harm. Psychological harm from false advertising is not included.

DNA tests and genetic tests, by the way, are considered "nonmedical tests", meaning that the results do not indicate a clinical condition that can be dealt with in a physician's office or hospital. Medical tests include blood cell counts, chemistry analysis, urinalysis, tissue examination. Newborn genetic testing is medical testing, since the tests look for the accumulation of specific substances in the blood. DNA testing (forensic, paternity, genealogical) and genetic testing for specific genes and/or mutations are nonmedical tests.

The most strict oversight of genetic testing laboratories comes from organizations that accredit and approve laboratories. Among these are the AABB (American Association of Blood Banks), CAP (College of American Pathologists), CLIA (Clinical Laboratory Improvement Amendments and CLIAC, Clinical Laboratory Improvement Amendments Committee), and ISO (International Organisation for Standards, specifically ISO 17025 for laboratories). All of these organizations offer voluntary accreditations for testing laboratories; only AABB specifically identifies accreditation for DNA testing (but not other genetic testing). The following URLs get you to the home page of these organizations:

http://www.aabb.org/Content/Accreditation/Parentage_Testing_Accreditation_Program/ptprog.htm

http://www.cap.org/apps/cap.portal?_nfpb=true&_pageLabel=accreditation

http://www.phppo.cdc.gov/clia/default.aspx

http://www.qualico.co.uk/html/iso_17025_lab_requirements.html

None of these organizations has any regulatory clout; they can only refuse or revoke accreditation. The closest to regulatory clout is the CDC (Centers for Disease Control), a federal agency that is primarily concerned with the spread of infectious diseases (influenza, sexually-transmitted, food poisoning).

Some states require that forensic or parental DNA testing be conducted by specific laboratories for the results to be considered acceptable in legal cases.

The Genetic Alliance, a group coordinating the activities of hundreds of support groups for specific genetic conditions, recently requested that standards for genetic testing be set and enforced by CMS (Centers for Medicare and Medicaid Services).

If you're thinking of DNA or genetic testing, check whether the company you are considering advertises accreditation by one or more of these organizations. Then--if you can--check to see whether the accreditation is current. This is possible for AABB by going to http://www.aabb.org/Content/Accreditation/Parentage_Testing_Accreditation_Program/AABB_Accredited_Parentage_Testing_Laboratories/ . None of the other organizations provide similar lists, but you can ask the company you are interested in by calling their toll-free number.

Whatever you do, remember the old adage: Buyer beware!

Marie Godfrey, PhD

Who will benefit from pharmacogenetics research?

Pharmacogenetics is the study of inherited differences in response to pharmaceutical drugs. One of the interesting issues lately has been the "discovery" that people of African-American heritage seem to react differently to drugs intended to reduce high blood pressure. Since the problem is more common among these people than those of other ethnic heritages, there seems to be some benefit to designing "ethnic" blood pressure medication.

What's funny to me is that, since the discovery of this effect, I haven't seen any drugs approved and advertised specifically for African-Americans. Perhaps this is the kind of result James Randerson was thinking of in the article I discussed yesterday, Risks of Online Genetic Testing.

Pharmacogenetics looks like a good thing. With it, doctors could match treatments to patients to speed up cures and minimise negative reactions to medication. Old drugs abandoned because of adverse effects in some test patients could be revived, if the effects' genetic basis can be understood. Ultimately, say evangelists for personalised medicine, your treatment will be tailored to your own genetic makeup. We would see a plethora of individualised panaceas.

As with genetic testing--which I discussed yesterday--Randerson feels the hype doesn't match reality. First, there's no incentive for pharma companies to develop genetic tests for response to an existing drug--unless the test could result in greater use of the drug.

For example, the experimental Alzheimer's drug rosiglitazone, currently in the final stages of clinical development does not appear to help patients in general; but when targeted at specific genetic subgroups it does seem to be effective. The result, to me, sounds like an attempt to save a drug that might otherwise be scrapped after costly clinical trials. I found a similar situation with a drug used against brain tumors: a genetic test--not available to the general public--may determine which patients are more likely to have successful results with the drug. If the test were more widely available, it might give more hope to those expected to be more susceptible to the drug.

For the second reason Randerson feels the hype doesn't match reality, there's the process of drug development. Now, think carefully--if you were a pharma company executive or board member, would you be likely to push further development of a drug that only affects a portion of the potential population of patients? Not likely. This situation is the case sometimes followed by a company who learns that their prospective new drug is metabolised by a family of enzymes in the liver called the cyp450 genes, which break down drugs and toxins. Because the cyp450 genes exist in different forms in different people, the new drug is not likely to be developed further if it is destroyed very quickly by the most common forms of the enzyme.

Yes, there are a fewdrugs on the market that are tailored to the patient's phenotype: the anti-cancer treatment herceptin, which works differently depending on which genes are expressed in the tumour, is in the vanguard; and drugs for psychiatric conditions are also likely to receive the pharmacogenetic treatment. I haven't checked into whether the geneticly determined susceptibility to these drugs was identified pre- or post-development.

So, according to Randerson, neither genetic testing nor pharmacogenetics is apt to dramatically change the medical landscape in the near future. Do you have a comment or opinion to add?

Marie Godfrey, PhD

Will genetic testing lead to a return to an interest in eugenics?

I've just finished reading an article in the Johns Hopkins Magazine, April 2006, called Raymond Pearl's "Mingled Mess". I had no idea who the person was, or what the mingled mess might be, but the word "eugenics" in the following struck me.

He made the case for eugenics, with "Breeding Better Men". . .then later went on to renounce the entire movement. Are there lessons for modern genetics? 

The article examined the history of eugenics, hoping to "illuminate difficult issues facing today's scientists as they navigate the ethically periolous terrain of modern genetics." 

Although I found the story of Pearl interesting, I was more interested in the end of the article, where the author Melissa Hendricks asks, "Is genetics . . . on its way down a slippery slope toward a new form of eugenics?"

DNA day, April 25, celebrates the report of the structure of DNA and the completion of the Human Genome Project. And many of the news articles will mention one of the latest proponents of eugenetics, James Watson-the co-discoverer of the DNA double helix. Watson has argued for genetically engineering the human germ line (eggs and sperm) to improve human beings and, he hopes, "lead to a society with fewer shy, ugly, or stupid children."

Geneforum, in its survey on gene doping, discusses the possibilities of producing better athletes by changing or adding genes. Another geneforum survey asks, "would you change your child's DNA if you could?"

All of these indicate to me that the public harbors a not-so-hidden thought that we can improve the human species by altering its DNA. Eugenics has this "good" intention. But, it also has another intention--to decrease the number of "defective" or "bad" people.

Hendricks asks, "how can we avoid a day when a future generation looks back and views today's time as a period when genetics was used unethically?"

One way to do this is to actively discuss and debate these issues. Another is to foster legislation and professional guidelines.

Kathy Hudson of the Johns Hopkins Genetics and Public Policy Center cautions against the "single-minded focus on genetics as an explainer for everything. The over-attention to genetics can mislead people because they're not taking in the full spectrum of environmental factors."

As the focus on genetic testing and identifying "the gene for . . " continues, we should also remember that there is no one gene for X, Y, or Z. The human genome contains so many modifying factors and the environment has so much effect on the expression of genes that a simple genetic code, trapped on a diagnostic chip is not the be-all and end-all of our future. Genes matter, but so do other things we tend to ignore. Let's broaden our minds and our approaches.

Marie Godfrey, PhD 

Would you donate your DNA?

YOU might donate blood to save someone's life. But, would you donate your blood, your DNA, and your most intimate medical secrets on a promise that it may help save a life years from now?

These are the questions asked in an article today in the New Scientist

Once again, the public is being asked to donate the code that makes each of them a unique individual to a study intended to link genes and diseases. Once again, the promise is cures of devastating diseases. Would you join the group that will donate a small blood sample?

You have a while to decide--unless you live in the UK or in Iceland. The project called Biobank is not expected to start in the US in the near future--it's still in the planning stage, according to the New Scientist. Here's how the Iceland, UK, and US projects differ:

The Icelandic studies focused on spotting gene variants in people who already have specific diseases or family histories of disease, and comparing them with those of healthy people. The proposed British and American studies are far more ambitious, as they will recruit people who are healthy at the outset and then wait to see which of them falls ill. Scientists will record environmental factors, such as people's diets, in real time, rather than relying on patients remembering what they ate in the past, in the hope this will help reveal factors other studies miss.

In addition,

...the organisers of the US project are considering using microchip-based devices such as rings, bracelets and body patches to keep a continuous check on volunteers' heart rate and blood oxygen levels. Participants' cellphones could be rigged up to transmit data on physiology and diet, and microchip-based sensors could be placed around the body to record other data such as exposure to radiation, or even what they consume, including alcohol and tobacco.

The £61 million UK Biobank project, funded by the UK Medical Research Council, the Wellcome Trust and the government health ministry, will rely more heavily on health records and diagnoses of family doctors to keep tabs on its subjects. It will also take detailed recordings of subjects' body fat, blood pressure and weight, use lifestyle questionnaires, and take blood and urine samples when people are recruited into the study.

Are we getting ever closer to carrying our genetic codes on our foreheads and transmitting to some "secure" database our actions, environment, and even our thoughts?

Marie Godfrey, PhD