deCODE scientists have discovered a single SNP that confers increased risk if inherited from the father, but is protective if inherited from the mother

Scientists at deCODE genetics, Inc. publish in the journal Nature the discovery of a version of a common single-letter variant in the sequence of the human genome (SNP) with a major impact on susceptibility to type 2 diabetes (T2D). The impact of the T2D variant is not only large, but unusual: if an individual inherits it from their father, the variant increases risk of T2D by more than 30% compared to those who inherit the non T2D-linked version; if inherited maternally, the variant  lowers risk by more than 10% compared to the non T2D-linked version. Nearly one quarter of those studied have the highest risk combination of the versions of this SNP, putting them at a roughly 50% greater lifetime risk of T2D than the quarter with the protective combination. This is the second largest effect of any genetic variant for T2D apart from SNPs in TCF7L2, discovered by deCODE in 2006.

“We could make this discovery beacause we are in the unique position of being able to distinguish what is inherited from the mother from what is inherited from the father. This we can do because of the large amount of data we have assembled on the Icelandic population. These data empower us in many ways. For example, using our ability to impute sequence data, we can multiply by 100 times the amount of information generated by sequencing one individual. We can use these tools to discover and integrate rarer variants into our tests and scans, identify drug targets for licensing, and put our know-how at the disposal of our service customers. We believe that this is an important advantage for conducting large-scale whole sequence studies over the next couple of years,” said Kari Stefansson, CEO of deCODE.

Because the risk is inherited and varies in this way, the SNP, located on chromsome 11, had never been linked to T2D even though it had been genotyped in large, traditional genome-wide association studies (GWAS). These do not distinguish between paternally and maternally inherited SNPs. But deCODE can track the parental origin of virtually any SNP in the genome of the tens of thousands of Icelandic participants in the company’s gene discovery work. In this study, deCODE used its population-wide genealogy database and proprietary statistical tools to determine the parent of origin of a number of SNPs in some 40,000 Icelandic participants in the company’s gene discovery programs. Some of these SNPs had previously been associated with different diseases and are located near “imprinted” genes – genes in which only the maternally or paternally inherited copy is “switched-on” to encode a protein. Five of these, one each in breast and skin cancer and three in T2D, showed that the parental origin of the variants affects the risk they confer.

The paper, “Parental origin of sequence variants associated with complex diseases,” is published online at www.nature.com, and will appear in the December 17 print edition.

As a deCODEyou reader, you have an active interest in how genetics can help to improve personal health and healthcare. If you are a deCODEme subscriber or have taken one of our DNA-based diagnostic tests, you have already followed up on that interest.

Then again, you may not have had your genome analyzed yet. You may simply be interested in taking part in research, having a scan, or simply in keeping up with the latest discoveries.

But whoever you are, your genome is information about you. And at deCODE, we believe that your genome belongs to you. Over the past decade we have worked with hundreds of thousands individuals who have decided to use their genome to advance our gene discovery work, to understand their risk of a certain disease, or who want to have a broad and constantly updated look at their genome through deCODEme. In every case, we think it is the individual who has the right to decide to use their genome and learn about it as they wish.

Our job is to find the variations in the sequence of the genome that have an impact on risk of disease, and to report to those who use our tests and scans what those findings mean to them. We have done a lot of this – more than anyone else. And because we take your genome as seriously as you do, our tests and scans only detect genetic risk factors that have been validated in multiple populations and to very strict criteria. Many of the risk factors we have found and test for in diseases like heart attack, type 2 diabetes and breast cancer account for a large proportion of the occurrence of these diseases. Some have as big an impact on risk as do some of the major lifestyle and environmental risk factors that are already a standard part of risk screening.

So when we hear august voices argue that you shouldn’t have the right to look at your genome if you want to, or that we shouldn’t test for genetic risk factors until we know everything there is to know about the human genome, we feel obliged to disagree. In this week’s New England Journal of Medicine, we have heard again that it is “too early” to measure genetic risk factors for common diseases. Why? In essence because in the coming years we are likely to discover many more genetic risk factors that will help to round out our understanding of all of the risk factors that exist. To be sure, we will discover more risk variants in a great many diseases. Many will be common but with little effect on risk. Others will be rare but will confer a high likelihood of disease and thus likely be useful components in genetic tests.

But since we already know risk factors that can nearly double the risk of heart attack, diabetes or breast cancer, in a substantial portion of the population, we take the much clearer view that there is an ethical responsibility to make tests for these risk factors available as widely as possible. As our CEO, Kari Stefansson, was cited as noting in the New York Times yesterday, our tests can identify people who are at several times average risk of major diseases, and there is nothing trivial about that sort of increased risk.

After all, we believe that testing for cholesterol is a good thing, even though our understanding of just how LDL impacts risk of heart disease in incomplete. Similarly, we are only now learning how to optimize the use of statins (and that our heart attack risk factor on chromosome 9p21 has been shown to be helpful for finding the best dose for individuals). How many lives would have been lost if we had taken statins off the market until that elusive day when we thought we understood everything about them?

In our view the challenge is rather to try to bring genetic risk factors into clinical practice as swiftly as possible. As an article this week in The Times points out, a deCODEme scan has a lot of actionable risk information in it. But one of the things we need to do is educate doctors about how to use such results  and how to integrate genetic risk into everyday screening. Our own experience with doctors is that most are very eager to learn. Moreover, genetic information complements what they already do and helps them to deliver better and more personalized medicine to their patients.

In the past few years we have made rapid strides in identifying the key genetic risk factors for some of the most common diseases in our society. Very large independent studies have established that detecting these risk factors can help individuals to act to protect their health and to get the treatments that are best suited to them. This is precisely the sort of information that is going to make it possible to transform our healthcare system into one that is both more effective and efficient – focused on preventing disease and treating it early, rather than spending vast sums of money once people are already seriously ill.

You and your genome are already at the heart of this transformation. If someone tells you that you need to wait, or that they will decide whether and what you can learn about yourself, you need to set them straight. We’ll be there with you.

Dr Edward M Farmer
Chief Communications Officer
deCODE genetics Inc.

deCODEme customer Anna Peterson on top of Acropolis on a camping trip in Athens.

By: Anna Peterson
I am a fit, healthy, 27 year old Canadian graduate student looking forward to the future. So why, you might wonder, did I decide to take the deCODEme genetic test? It’s simple really. Information is the key to prevention. By learning about my genetic predisposition for different illnesses, I will be better prepared to take an active role in my future health care decisions.
Many of my friends were surprised that I decided to take this comprehensive genetic test. Some were curious about the story my genes would tell, while others wondered whether or not I really wanted to know. When I put my genetic sample in the mail, I felt a little nervous about the chain of events I had set in motion, but curiosity overcame fear. In my opinion, knowledge is power and I’d rather make lifestyle changes in my 20s than in my 60s.

It wasn’t just curiosity that prompted me to take the deCODEme test. I was particularly interested to better understand my genetic predisposition to both breast cancer and age-related macular degeneration (AMD). According to the Canadian Cancer Society, one in nine women is expected to develop breast cancer in her lifetime. While I have been familiar with this statistic for a long time, it becomes much more real when someone you know is affected. Two and a half years ago, my mother’s sister was diagnosed with breast cancer. At arm’s length, I witnessed the impact of a breast cancer diagnosis. This experience, however, did little to prepare me for the phone call I received in June of this year. Tearfully my mother told me how she had found a lump in her breast and that a recent biopsy had confirmed the lump was indeed cancerous. In a few short moments our lives changed forever. Sharing this difficult journey with a woman I love and admire has been a harrowing privilege. But I couldn’t help wondering if I might find myself in a similar position one day. Still years away from my first mammogram, I thought why wait for time to tell. No matter the results, I wanted to know my relative genetic risk of developing breast cancer.

Anna Peterson: "Prevention Starts with Knowing the Odds."

When I logged onto the deCODEme web site to explore my results, I spent several minutes avoiding the link to the breast cancer assessment. A very human hesitation, but I soon realized there was no point staying in the dark. The deCODEme test examines eight genetic variants found to increase the risk of developing breast cancer. The BRCA1 and BRCA2 genes (found in 2-5% of women with breast cancer) are not included in this assessment. My results indicate that the relative genetic risk for someone with my genotype is 1.23. This corresponds to a 14.7% lifetime risk of developing breast cancer, which is 23% greater than for females of European ancestry in general. Not the best news, but certainly not the worst.
To better understand my results, I contacted Dr. Kris Kristjansson, a genetic counselor at deCODE genetics. He stressed that the deCODE test is not a diagnostic tool, so there was no need to be alarmed by what I had learned. He explained the scientific details of my test results in simple terms and brought the Gail Model risk assessment tool to my attention. This tool, originally developed for physicians and now freely available on the web, calculates the impact of non-genetic factors to estimate a woman’s five year and lifetime risk of developing breast cancer. Taken together, the deCODEme test and the Gail Model provide a more complete approximation of a woman’s lifetime risk of developing breast cancer. Entering my age at 35, the Gail Model risk assessment tool estimated my lifetime risk of developing breast cancer at 17.6%, which is above the average 12.6% lifetime risk. To calculate the combined assessment I simply multiplied my deCODEme result of 1.23 with the Gail Model result of 17.6 for a total of 21.6. I now know that I am at higher risk of developing breast cancer from both genetic and non-genetic factors. With a 21.6% lifetime risk of developing breast cancer, I will have to be vigilant. Letting out a breath I didn’t realize I was holding, I still felt good about my choice not to walk blindly into the future. The results of my deCODEme test and the Gail Model have given me the tools to advocate for early screening and a renewed commitment to making positive lifestyle choices.

Anna Peterson on a backpacking trip.

How we live our lives today has a tremendous impact on the quality of life we will enjoy in the future. I chose to take the deCODEme complete scan because I also wanted to learn about my genetic predisposition for developing age-related macular degeneration (AMD). My grandmother developed AMD in her mid 70s and, for years, I have wondered if I would one day be among the 40% of Canadians over the age of 75 to develop AMD. I was born with an untreatable visual impairment in one eye and the challenges of growing up with limited sight have made me uniquely aware of the reality of blindness. I have silently worried about the possibility of one-day loosing my sight in both eyes. The deCODE genetic test revealed that the lifetime risk for someone with my genotype is only 2%, which is 75% less than for people of European ancestry in general. I am delighted to know that I have excellent genetic chances of avoiding this debilitating illness.
Before taking the deCODEme test, I never gave skin cancer a second thought (save to lather on sunscreen at the beach). Yet skin cancer is one of the most common cancers in the world. According to the National Cancer Institute of Canada, environmental and genetic factors are thought to play a role in basal cell carcinoma, which accounts for 80% of all skin cancers. Scientists at deCODE genetics have identified two genetic variants that appear to act independently from exposure to UV radiation.
It never occurred to me that I might be genetically predisposed to developing basal cell carcinoma. So you can imagine my surprise, when my results indicated a 45.9% lifetime risk for someone with my genotype. A few days ago, I knew nothing about basal cell carcinoma and now I’m beginning to realize I might come to know this disease all too well in the future.
Eager to learn more, I called home to speak with my parents. My test results provided the perfect opportunity to discuss our family medical history. I soon learned that my grandfather had “skin cancer” (possibly basal cell carcinoma) in his late 60s. For the first time, I understood my mother’s frequent visits to the dermatologist to have moles examined or removed. While she had been aware of a potential risk to herself, none of us had considered that I might also be at risk. No need to panic, however. In fact, I am grateful for the knowledge and the opportunity to take the steps necessary to protect myself now and hopefully avoid this illness in the future.

Anna Peterson camping

Genetic testing is a revolutionary way to protect yourself and the ones you love from unknowns and potential future illness. My genetic makeup isn’t going to change but, through this experience, I have changed. I’ve relaxed my concerns about 13 diseases (AMD, glaucoma, multiple sclerosis, etc.) and have learned of other conditions such as breast and skin cancer that I can now keep an eye on in the future. Empowered by a greater understanding of my genetic predisposition to different illnesses, I have become even more proactive about prevention.

Anna Peterson

A new genetic test assessing a woman's risk of developing the most common forms of breast cancer has arrived. Can the test, developed by the biopharmaceutical company deCODE, improve the way doctors screen for breast cancer?

Breast cancer kills 40,000 people a year in the U.S. This is about the population of Atlantic City, New Jersey. Imagine, each year an entire city wiped out by breast cancer.

To help fight breast cancer, a new test assessing individual risk has just become available. For women without a clear family history of the disease, the deCODE BreastCancer^TM test assesses their personal risk of developing the most common forms of breast cancer. The DNA test, launched by the biopharmaceutical company deCODE, makes it possible to identify those women at significantly higher than average risk, helping doctors use new screening technologies and treatments in a more targeted, personalized and effective manner.

The key to fighting breast cancer, like all cancers, is early detection, which is why the medical field is buzzing over deCODE’s new breast cancer test.

“This test helps define individual prevention which is what so many of my patients want,” says Owen Winsett, MD, founder and director of the Breast Center of Austin.

Dr. Winsett, who has already ordered the test for 25 of his patients, can’t hide his enthusiasm over how the decode breast cancer test is changing the way he screens for the disease.

“I’m excited to be able to extend my screening and prevention practice. I plan to make this test a standard tool for helping me decide which of my patients may benefit from screening at an earlier age, or benefit from more intensive screening, including breast MRI’s. And then if my patients don’t have breast cancer, to motivate them to begin healthy preventive strategies.”

The test is not offered directly to individual women, but rather ordered by doctors on the request of their patients. deCODE advises that the test-which scans a woman’s genome for seven widely replicated single-letter variations (SNPs) in the human genome that are linked to increased risk of breast cancer-is a way to better connect doctor and patient.

Dr. Winsett agrees. He recommends that before taking this test women should consult their general practitioner, and if their doctor is uncertain about how to use the results of the test, to seek out a breast cancer specialist.

Like all new technologies – particularly those that may change accepted clinical practice – this type of risk screening has raised concerns in some quarters. Some critics have argued that the test is not accurate enough because it’s not based on a large enough sample of women to predict risk of breast cancer. However, the evidence tells a different story. According to Dr. Winsett, epidemiological studies on breast cancer present a fairly straightforward argument that deCODE’s genetic test does indeed give a picture of a patient’s baseline risk. The evidence shows that the seven SNPs in the human genome that the decode test scans for are linked to an estimated 60 percent of all breast cancer cases. These findings are derived from integrated data from discovery and replication studies published in major peer-reviewed journals and involving nearly 100,000 breast cancer patients.

“I remind patients this test is one peice of the puzzle,” says Dr. Winsett. “The test won’t tell patients if they will get breast cancer or if they won’t. It shows the average risk, and then says where a woman stands in relation to that average and then what her absolute risk is. As a doctor, deCODE’s breast cancer test helps me evaluate a patient and make a future plan for prevention and testing.”

Still, some non-clinicians feel genetic testing only benefits women who have a strong family history of breast cancer. One bioethicist recently wrote on an MSNBC blog that “the tests Decode and other companies are offering are more likely to empty family pocketbooks and leave women with a false sense of security than they are to prevent breast cancer.”

Dr. Winsett finds this argument muddled. There are already tests to pick up genetic risk factors for highly familial forms of the disease, and neither those tests nor deCODE’s for measuring risk will cure or prevent breast cancer. Dr. Winsett notes that mammograms, ultrasounds and breast MRIs don’t prevent women from getting breast cancer either, but doctors still use them because they are tools to help detect breast cancer.

“Sometimes a patient will say, ‘I’ve had a mammogram regularly, so how can I get breast cancer?’ It’s easy to think that. But neither mammograms nor the deCODE test can on their own prevent breast cancer. It’s how you use the information from the genetic test to shape a patient’s care that leads to prevention or early detection.”

Genetic risk screening for breast cancer might sound like cutting-edge medicine, but doctors have been using genetics to assess risk of developing breast cancer for years. There are genetic tests that look for mutations of the BRCA 1 and BRCA 2 genes. Variations in these genes are linked to the rare and essentially purely genetic forms of breast cancer.

While detecting the BRCA variants is considered very valuable information to women with a family history of the disease, doctors and researchers knew genetics would one day play a bigger role in the remaining 95 percent of breast cancers. The deCODE BreastCancer^TM test is aimed squarely at filling this gap, and to broadening the use of genetics in fight against breast cancer.

When a woman’s genome is scanned with deCODE BreastCancer, deCODE’s CLIA-registered laboratory checks for certain versions of seven single-letter variations in the genome, called SNPs. According to which versions are detected, that woman’s risk is then tallied, adding together the risk of each of the seven SNPs, to yield a score in relation to average risk, which is about 12% for American women of European origin. By multiplying the relative risk by the average, the results also provide a score of a woman’s absolute risk of developing breast cancer in her lifetime.

Depending upon a woman’s assessed risk, her doctor may suggest that she receive regular mammograms earlier than age 40, the standard starting age in the United States. If the test reveals a high risk, clinicians like Dr. Winsett might order a more advanced breast MRI or an ultrasound test for his patient. In some cases, high-risk patients with other contributing risk factors might start on a course of treatment to reduce the risk of tumors.

Decode’s breast cancer test is not a silver bullet. It won’t cure cancer. It measures risk and will be used in conjunction with other diagnostic tools and treatments to reduce the impact of the disease. But by using deCODE’s genetic test to find out which patients have a higher risk for the disease, says Dr. Winsett, earlier detection of breast cancer is possible.

“With the advent of deCODE’s breast cancer test we can intervene before the cancer happens. My hope is that we’ll see fewer breast cancers. I’m in business of dealing with breast lumps. I’m hoping this test can help reduce the breast lumps that I see.”

Breast Cancer Network of Strength was started by Mimi Kaplan and Ann Marcou.

Attitudes towards breast cancer have changed quite a lot over the past three decades, a fact evidenced by the outpouring of response when stars such as Olivia Newton-John, Kylie Minogue, and, most recently, Christina Applegate, went public with their personal struggles with the disease. But this change in attitude is also reflected in many other ways and not least in the adoption of a new name for the patient advocacy and support organization that until now called itself Y-ME? Tomorrow, a gala event held at the Fairmont Hotel in Chicago will celebrate Breast Cancer Awareness Month and the evolution of Y-ME, 30 years on, into the Breast Cancer Network of Strength-a change they hope that will better communicate the organization’s mission to promote a proactive, engaged and positive approach to fighting breast cancer.

Started in 1978 by librarian Mimi Kaplan and social worker Ann Marcou (both breast cancer patients hailing from Chicago), the newly named Breast Cancer Network of Strength includes a 24-hour hotline with interpreters in 150 languages, as well as an internet-based support system where breast cancer patients can share their stories. Breast Cancer Awareness Month (BCAM) has a slightly shorter history but the pink ribbons you have seen everywhere for the past two weeks (one of which you are hopefully wearing right now) are now a familiar sight worldwide.

Alongside a number of other organizations, deCODE genetics is working on the preventative side of matters via ongoing research into the genetic risk factors for breast cancer. Last week deCODE genetics launched deCODE BreastCancer^TM, a new tool for assessing risk of the common forms of breast cancer (that are also the result of environmental and lifestyle factors) and for targeting intensive screening and early detection for women at high risk of the disease. deCODE BreastCancer^TM aims to put the power of genetic risk assessment to work for the majority of women, complementing the use of tests for variants in the BRCA1&2 that cause rarer, highly familial forms of the disease.

MainStreet.com – How to Fight Breast Cancer Without Giving Money

Breast Cancer Network of Strength

On October 8th MSNBC published an article by Arthur Caplan, Ph.D. on genetic tests for breast cancer.
The following is a response by Jeff Gulcher, M.D., Ph.D, Chief Scientific Officer at deCODE Genetics.

Arthur Caplan stresses caution in the application of the new genetic risk tests for common diseases and I certainly agree that genetic testing should be applied with care. However, he goes too far when he says that the new deCODE BreastCancer genetic risk test is only useful for women who have two or more close relatives with breast cancer, is not based on large enough studies to be accurate, and is not regulated.

There are two major types of breast cancer: the rare, early onset form that occurs in certain families and for the detection (for which the Myriad Genetic test is well suited), and the common form which accounts for 95 percent of breast cancer. The vast majority of women who develop breast cancer do not have the conventional risk factors of family history, pregnancy history or breast density. Unfortunately, many of these women were likely considered to be of average risk before their cancer was found. Therefore, they were not even offered screening with breast MRI which detects two to three times more cancer at an earlier stage than mammography alone, or preventive measures such as tamoxifen treatment which can cut down cancer rates by 40 to 50%.
To date, the healthcare system has not been as good as it would like to be at predicting which women are at higher risk of the common forms of breast cancer: But we at deCODE and others have invested years of research and tens of millions of dollars to find other factors that can complement the conventional factors. Our efforts have paid off, because there are 7 genetic markers, easily and accurately measured from a cheek swab, that define most of the genetic risk for the common forms of breast cancer. The test defines risk from 0.4-fold to 4-fold compared to the general population risk (the average woman of European ancestry in the US has a lifetime risk of 12%). Based on this test alone, 10 percent of women have risks ranging from 1.4- to 4-fold, and would account for about 17 percent of breast cancer cases. Five percent of women are at more than 2-fold average risk, and the 1 percent are at 3-fold risk, so the risk is substantial for a significant portion of the population.

This risk is independent of family history and other conventional risk factors and therefore may identify some women as having higher risk even if breast cancer does not appear to be in their families. So Arthur Caplan is fundamentally incorrect in stating that only women with a family history of breast cancer would benefit from genetic testing. That may be true for traditional genetic diseases like Huntington’s disease and the rare highly familial form of early breast cancer addressed by the Myriad test, but the new tests for common diseases define risk beyond family history.

Each of the genetic markers in this risk test have been replicated in between 5 and 30 different populations in studies by deCODE genetics, the National Cancer Institute, and UK Cancer Research. These studies have been published in the most prestigious, peer-reviewed journals, including Nature Genetics and the New England Journal of Medicine. Altogether almost 100,000 patients and controls have been studied to define the marker risks. We made this test available for physicians to order for their patients through our reference laboratory which is regulated under CLIA by the US Federal government.

However, it is important to emphasize that the test does not diagnose breast cancer: it is simply a means of assessing personal risk of the disease, much more analogous to an LDL-cholesterol test for assessing heart disease risk than traditional genetic tests for purely genetic rare disorders like that for Huntington’s disease. That is, women at higher risk based on deCODE Breast Cancer are not destined to develop breast cancer. They may have a 20 to 36 percent lifetime risk for developing cancer (versus baseline risk of 12%). Women at lower risk are not immune from breast cancer and therefore would still be regularly screened with mammography. Women at higher risk above a certain threshold may benefit from more intensive screening using breast MRI on top of mammography, as recommended by the American Cancer Society. Also, certain medications such as tamoxifen which blocks the estrogen stimulation of breast cancer cells are approved by FDA to reduce breast cancer risk for women at higher risk.

In summary, this test may reclassify as higher risk some women who were previously considered to be of average risk, contributing to earlier detection and more focused prevention strategies. In fact, this test together with family history could define as higher risk the roughly 20% of women who may account for 35 to 40% of future breast cancers.

Looking at the big picture, about 5 percent of the health care budget is used for diagnostics and most of the rest is for therapeutics. Much money has been invested in the development and use of new expensive therapies for women with advanced cancer. But individual women and our healthcare system may both benefit from the increased use of risk diagnostics to help to focus on women at higher risk and thus diagnose cancers earlier rather than later, saving lives, suffering, and money.

Anyone who wants to hear some real stories from real people about how genetic tests like this may improve healthcare can find them on this blog.

Jeff Gulcher MD PhD
Chief Scientific Officer
deCODE Genetics

deCODE Breast Cancer enables women to understand whether they may benefit from more intensive screening, monitoring or preventive drug therapy.

Reykjavik, ICELAND, October 8, 2008 – deCODE genetics today announced the launch of deCODE BreastCancer™, a new tool for assessing risk of the common forms of breast cancer. For the first time, a woman concerned about breast cancer can speak with her physician about a genetic test to better understand her lifetime risk of developing the common forms of the disease.

The common forms of breast cancer result from the interplay of genetic as well as environmental and lifestyle factors and represent 95 percent of all breast cancers. These are distinct from the rare and essentially purely inherited forms of the disease due to mutations in the BRCA1 and BRCA2 genes, which cause between 1 and 3 percent of breast cancers. deCODE BreastCancer™ is a DNA-based reference laboratory test performed using a simple blood sample or cheek swab, ordered by physicians on behalf of their patients.

“This test is simple and compelling because it provides a woman and her doctor a means of understanding her personal risk of developing the common forms of breast cancer. This information is well-validated, relevant to the vast majority of women, and independent of family history and other known risk factors. Combined with the high public awareness of the importance of screening, advances in magnetic resonance imaging (MRI) technology and the availability of preventive drugs targeting estrogen receptors, I believe this test will help to save lives,” said Dr. Kari Stefansson, M.D., Dr. Med., CEO of deCODE.

“DNA-based breast cancer risk assessment has to date been focused on detecting rare mutations that confer very high risk of early onset breast cancer. These are very valuable tests, but they do not measure genetic risk of the common forms of the disease.  The DNA markers identified recently by deCODE represent an important step toward filling current gaps in our understanding of breast cancer risk.  Ultimately, the goal is to deliver more personalized prevention and treatment for a much greater number of women,” said Rebecca Sutphen, M.D., Clinical Geneticist at Moffitt Cancer Center and Advisory Board member at Informed Medical Decisions, Inc., a network of genetic counselors who provide support to physicians and patients using deCODE’s tests.
“We speak to many people who are concerned about breast cancer through our 24/7 YourShoes Breast Cancer Support Center,” said Margaret C. Kirk, CEO, Breast Cancer Network of Strength (formerly known as YME National Breast Cancer Organization). “We are very interested in all advances that could empower people to take charge of their health care and better understand their risk for developing breast cancer.”

Owen Winsett, M.D., founder and director of the Breast Center of Austin, Texas, commented: “I have followed closely the recent scientific discoveries that are incorporated into this test. I am excited to be able to extend my screening and prevention practice, because this test applies to so many more women than the BRCA1 and BRCA2 tests. My patients are eager for this type of risk information and appreciate that the test can be done with a painless inner-cheek swab. I have ordered several tests on an early-access basis and plan to make this test a standard tool for helping me to decide which of my patients may benefit from screening at an earlier age, breast MRIs, and other risk reduction measures. This test helps define individual prevention, which is what so many of my patients want.”

The deCODE BreastCancer™ test measures seven widely replicated single-letter variations (SNPs) in the human genome that deCODE and others have linked to risk of breast cancer. These SNPs contribute to the incidence of an estimated 60 percent of all breast cancers. The test integrates data from discovery and replication studies published in major peer-reviewed journals and involving nearly 100,000 breast cancer patients and healthy volunteers from many populations, principally of European descent. deCODE and other organizations are conducting replication studies to validate these markers in populations of other continental ancestries.

Women taking the deCODE BreastCancer™ test will receive a numerical score representing their relative risk of developing breast cancer in their lifetime compared to that of the general population as well as their personal lifetime risk. According to the American Cancer Society, average lifetime risk for women of European descent is 12 percent. Test scores range from 4.0 times average lifetime risk to less than half, or 0.4-times. The risk assessed by deCODE BreastCancer™ is independent of conventional risk factors such as family history of breast cancer in close relatives, age at first menstrual period, pregnancy history, and breast density. Therefore, this genetic risk should be viewed in the context of other risk factors assessed by a woman’s physician.

deCODE BreastCancer™ can identify the roughly 5 percent of women who are at a greater than 20 percent lifetime risk of the common forms of breast cancer (about twice the average risk in the general population), and the 1 percent of women whose lifetime risk is roughly 36 percent (about three-times average). According to ACS guidelines, women with a lifetime risk of 20 percent or greater should receive annual MRI breast screenings in additional to mammograms, and women at 15 to 20 percent lifetime risk should talk with their doctors about the benefits and limitations of adding MRI screening to their yearly mammogram. With the information provided by the deCODE BreastCancer™ test, an additional 15 percent of women may fall within this range of moderately increased risk.

The test also predicts which women are more likely to develop ER-positive breast cancer if they develop cancer at all. This is important because these women may be more likely to respond to prevention strategies with drugs like tamoxifen that target estrogen receptors. The American Society of Clinical Oncology (ASCO) recommends that women with a five-year risk of 1.66 percent or greater should be considered for preventive treatment with tamoxifen.

deCODE BreastCancer™ may also be used to modulate the risk profile of the early onset inherited forms of breast cancer in women who have tested positive for risk variants in the BRCA1 or BRCA2 genes.

How to order deCODE BreastCancer™
Additional information and physician order forms for deCODE BreastCancer™ can be found at www.decodebreastcancer.com. The price of the test is $1625 dollars and deCODE facilitates filing for reimbursement with commercial insurers. Testing is performed in deCODE’s CLIA-registered laboratory, which has analyzed the genomes of hundreds of thousands of people from around the globe.

About Breast Cancer
Breast cancer is the most common cancer and the second leading cause of cancer deaths among women, according to the World Health Organization. The ACS estimates that 182,400 new cases of invasive breast cancer will be diagnosed in the United States in 2008, resulting in more than 40,000 deaths.

Breast cancers are classified as ER-positive or ER-negative according to whether tumors are found to contain estrogen receptors. In women of European descent, approximately three-quarters of breast cancers are ER-positive, and in women of African descent, approximately 50 percent are ER-positive.

Although a substantial portion of risk of breast cancer is inherited, it has taken painstaking research to find genetic variants predisposing to the disease’s common forms. The mutations in the BRCA1 and BRCA2 genes conferring very high risk have a less than 0.5 percent frequency in the general population in the United States and Europe, accounting for only 1-3 % of all breast cancers.

Identifying and enabling the detection of a substantial proportion of the genetic risk for the common forms of breast cancer is the goal of deCODE’s gene discovery work in breast cancer and the deCODE BreastCancer™ test. Women who know they are at a higher than average risk of breast cancer can also make proactive lifestyle changes to lower their lifetime risk, according to ACS. These include staying physically active, maintaining a healthy weight, eating healthy foods, and limiting alcohol intake and smoking.

About deCODE
deCODE is a biopharmaceutical company applying its discoveries in human genetics to the development of diagnostics and drugs for common diseases. deCODE is a global leader in gene discovery — our population approach and resources have enabled us to isolate key genes contributing to major public health challenges from cardiovascular disease to cancer, genes that are providing us with drug targets rooted in the basic biology of disease. Through its CLIA-registered laboratory, deCODE is offering a growing range of DNA-based tests for gauging risk and empowering prevention of common diseases, including deCODE T2™ for type 2 diabetes; deCODE AF™ for atrial fibrillation and stroke; deCODE MI™ for heart attack; deCODE ProCa™ for prostate cancer; deCODE Glaucoma™ for a major type of glaucoma; and deCODE BreastCancer™ for the common forms of breast cancer. deCODE is delivering on the promise of the new genetics.

With this latest discovery, the genetic factors underpinning a very significant proportion of inherited risk of ER+ breast cancer have now been elucidated. Common variants previously discovered by deCODE are together involved in an estimated 25% of ER+ breast cancers.

deCODE made today’s discovery through the analysis of genotypic data from a total of nearly 40,000 patients and control subjects from five countries. deCODE gratefully acknowledges the participation of the patients and researchers who took part in this study.

Link: Read the paper, ‘Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer’, in Nature Genetics