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."

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.

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 3^rd 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%.

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.