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

By Edward Weinman

With a simple swab from the inside of your cheek, deCODE genetics can scan your DNA, map your markers and assess your risk of developing 29 common diseases. Edward Weinman, self-described hypochondriac, wonders if he should look too closely at his possible future.

Fifteen hundred Americans will die of cancer today. Tomorrow, another 1,500 will perish. And the day after tomorrow: yet another 1,500.

While I’ve never had cancer (knock on wood) I know how the disease changes lives. My grandmother died from it. My brother has non-Hodgkin’s lymphoma, although thankfully it’s currently in remission after a lengthy round of chemotherapy. Cancer is scary. It accounts for one out of every four deaths. According to the American Cancer Society, cancer is the second leading cause of death in the US, behind heart disease.
Oh, yeah. Heart disease. The great American killer. Heart disease kills 652,486 Americans per year, according to the National Center for Health Statistics. Let’s not forget Alzheimer’s, no pun intended. This cruel disease that strips us of our memories is the sixth leading cause of death, and rising. Every 71 seconds, someone develops Alzheimer’s, including my mother. It’s hard to face the fact there is almost nothing we can do about some diseases, except prepare ourselves and our loved ones for the eventuality.
On the other hand, there are so-called killer diseases on which we can have a positive impact. We cut back on fatty foods and load up on vegetables. We increase our daily intake of fiber by eating cereal that tastes like bark dust. We pop vitamins. We spend time in the gym, going from workout station to workout station like a rat in a cage. Some of us work through crossword puzzles in the hope that mental gymnastics will keep plague from forming in our brains.

But are these healthy habits enough? Is there something more I can do to protect myself from these killer diseases?

For about $1000, deCODE will scan my genome for genetic markers linked to such killers as heart disease, diabetes, certain types of cancer and Alzheimer’s. All that’s required is for me to order a kit, swab the inside of my cheek, drop the swab into the mail, wait a few weeks and then log on to decodeme.com to view my results.

According to deCODE, discovering an inherited propensity toward a particular illness can motivate individuals to get more frequent checkups, take preventive medicines or make lifestyle changes to try to ward off the specter of disease.

But is it really a good idea for a hypochondriac like myself to know my own DNA? What if I discover that I have a high risk of heart disease? Will I soon be hauling myself off to the ER complaining of chest pains? Until recently, my view is that it would have been better to live and hope for the best rather than discover I have a high probability of developing a fatal condition. Ignorance is bliss.

Then my mother fell ill. And my brother got sick. As far as my own health, I exercise like a banshee. However, despite all the hours logged in the gym, I’ve taken more than one trip to the ER because of chest pains. I’ve had EKGs, stress tests, even a CT angiogram which all revealed that my heart was strong. The cause of my chest pains: stomach ulcers and, later, anxiety. But that helpless feeling of lying in the ER as doctors connect EKG leads to my chest sometimes returns. I worry about my health more than most 41-year-olds. So maybe a genetic test is exactly what I need to put my mind at rest.

Yes, I want to arm myself with as much information as possible in order to fight what might be coming, or at least prepare for what might await me on the horizon.

“We need to empower people,” says Dr. Robert Superko, author of the book Before the Heart Attacks, and executive director of the Center for Genomics and Human Health at the St Joseph’s Translational Research Institute. “If a genetic test prompts people to do what’s right for them then we have accomplished our goal.”
I order the kit.

Sitting at my laptop, logged on to deCODEme.com, the genetic secrets to my future health are only a mouse click away. I can click to see my inherent risks of contracting all 29 of the diseases deCODE tests for, or click on the results one disease at a time, leaving the scary diseases for later, or not at all. It’s my choice.

I’m not really concerned about whether or not I’m lactose intolerant. I’m not too worried about Celiac disease, or restless-leg syndrome. No, I’m sweating over the Alpha diseases: Prostate Cancer. Alzheimer’s. Heart Disease. What if my test results portend to a future weighted down by Chemo, or if I’ll one day take Arecept, or have a stent inserted into my arteries?

I demur. You know, no news is good news. The last thing a hypochondriac like myself needs is a fortuneteller mapping out my future in a pack of tarot cards. I understand that information is power, but what about Alzheimer’s? If my risk is relatively high, I can whittle down pencil after pencil working on the NY Times crossword and not really reduce my risk, even if I throw in a few Sudoku puzzles for good measure.
“The test is a way of bringing patient and doctor together,” says Dr. Jeffrey Gulcher, deCODE’s chief scientific advisor. “The test gives you a risk assessment, and then you and your doctor can figure out what to do about it.”

So the test is not definitive. It’s not a diagnostic tool in the usual sense. If I have a higher than normal inherited risk of heart disease that doesn’t mean I have to replace my artery clogging Ben & Jerry’s Chocolate Fudge Brownie with apple slices. If my risk of Alzheimer’s is high I’m not going to have to purchase an identity bracelet with my name, address and phone number engraved on it in case I get lost.

“The genetic test is analogous to a cholesterol test,” says Dr. Gulcher. “Just because you have high cholesterol, doesn’t mean you’ll have a heart attack. Just because you have low cholesterol, doesn’t mean you’re off the hook.”

I breathe a sigh of relief. I can look at my results without breaking out into a cold sweat. My DNA results aren’t going to say: “Tomorrow, Edward Weinman, you’ll contract cancer.”

Then again, Dr. Gulcher’s recent health issues suggest that comparing the deCODEme genetic test to a cholesterol screening is not all together an accurate analogy. Months ago, Dr. Gulcher took the swab, and his genetic profile revealed that he had a 30 percent lifetime risk of contracting prostate cancer. At 48, Gulcher was still two years away from when most medical experts believe prostate screening should begin.
How did Dr. Gulcher take the news? He was empowered. Dr. Gulcher took a standard blood test measuring his prostate-specific antigen, or PSA, which showed he was at the high end of normal. This data, combined with Dr. Gulcher’s DNA test, compelled his doctor to refer Gulcher to a urologist who performed an exploratory biopsy. The biopsy’s result? “A fairly aggressive form of cancer,” Dr. Gulcher recalls. Thankfully, Dr. Gulcher’s cancer had not spread to other parts of his body, and he underwent surgery to remove the cancer. Dr. Gulcher has just had his catheter removed when I ask him if deCODE’s genetic test saved his life.
“I can’t say for sure, but it’s likely it did. I had a tumor at the time of diagnosis. There is a good chance that tumor would’ve already spread” by the time he went in for a normal PSA screening at the age of 50.
Okay, I’m convinced. Time to decode my DNA. I click on the link and my test results are revealed:
My relative genetic risk for Alzheimer’s is 1.74, translating into a lifetime risk of 10.5 percent.

Not so bad, right? Not exactly. The average risk of contracting the disease is 6.4 percent. So I’m higher than average. But what stands out like a scar on a model’s face is when I look at the percentage of the population at a less or equal risk to me: 97.2 percent. In other words, only 2.8 percent of the population has a higher risk of contracting Alzheimer’s than I do.

So what does this mean?

“We emphasize that these are not determinative factors. They reflect risk. Relative risk,” Dr. Gulcher tells me.
He’s got a point. When I look at my risk of becoming obese I realize these results must be taken with a grain or two of salt. My DNA says that my relative genetic risk for obesity is .80, translating into a 31.6 percent chance of becoming fat. I chuckle, because I work out four to five days a week, and I’m what you might call skinny, or as I prefer, lean and toned. Plus, my metabolism works at hyper speed. At 41, I can proudly say that I have a six-pack. So a 31.6 percent risk of becoming fat? I don’t think so. (There’s no need to elaborate more because this grain or two of salt is refuted below, in that the test is necessary, and one that can improve health. One must always present the counter argument to make the argument stronger.)
Again, deCODEme only provides me with information on my “relative” risk of contracting common diseases. It’s not definitive. But can’t I just look at my parents’ and grandparents’ health and the health of my siblings to decode what diseases might afflict me when I grow older? Do I really need to pay $1000 for a genome scan?

“That would work well for certain diseases, like certain types of breast cancer, but common diseases tend to skip generations. Most of us don’t keep track of our genealogy. But that’s what’s going on when we find these common variations.” Dr. Gulcher continues: When we run a test “we are percolating the risk through your family’s history of disease.”

Dr. Gulcher then asks me a question. He curiously wants to know what my top two diseases are in terms of risk. I figure Alzheimer’s is number one, until I scan down my gene profile and learn that I have a 2.3 relative genetic risk of developing Type 2 Diabetes, translating into a 57.5 percent lifetime risk, double the average lifetime risk.

Not a chance. No way is it possible that I’m at risk for diabetes. I’m healthy. I eat right. I exercise. I’m not even close to being overweight. My BMI is perfect. I went so long during my last stress test that the cardiologist asked if I ever ran cross-country competitively. How can I be at risk for Type 2 Diabetes? Surely this proves deCODEme’s genetic test must be taken with many grains of salt. Perhaps this invalidates all my other results.

The doctor draws my blood and ships it off to the lab.

A few days later, I find out that my fasting glucose level is 96 mg/dl. That’s the high end of the normal range but a lot higher than I expected. One indication of pre-diabetes is a fasting glucose level that is between 100 and 125 mg/dl. Talk about a wakeup call. Despite my healthy lifestyle, my glucose levels are too high and that can be nothing other than genetic.

I remember Dr. Gulcher’s words: “The test is a way of bringing patient and doctor together. The test gives you a risk assessment, and then you and your doctor can figure out what to do about it.”
There’s no need to panic, but it is time to make an appointment to see my doctor. It’s time to trade in my Ben & Jerry’s for those apple slices.

Edward Weinman is a freelance writer living in Los Angeles, and a contributor to deCODE’s News Blog. He spent eight years in Iceland, working as a journalist and he co-wrote the film A Little Trip to Heaven.

Chief scientific officer of deCODE, Jeff Gulcher (48) takes a deCODEme scan that indicates he has a very high risk bracket for prostate cancer. Taking his results to a urologist may have saved his life.

Rick Weiss of the Washington Post reports:

Jeffrey Gulcher had no reason to think much about prostate cancer. He was just 48, and the disease typically strikes later in life. Even the most cautious medical groups agree that most men need not begin annual prostate screenings until age 50.

But Gulcher happens to be the chief scientific officer of deCODE Genetics — one of several companies that, amid some controversy, have begun offering direct-to-consumer DNA tests that can help people predict which diseases they are likely to get. So in April, he spat into a test tube and, without giving the matter much thought, sent the sample in for analysis by his own company.

He was in for a shock.

The test indicated that he carries a genetic variant that nearly doubles his lifetime risk of getting prostate cancer: While the average man has a 15 percent chance of being stricken, Gulcher had a 30 percent shot. That spurred his physician to order a standard blood test for prostate cancer. The result was toward the high end of the range considered normal, which, together with the DNA test, worried the doctor. He referred Gulcher to a urologist, who performed an exploratory biopsy — and found that Gulcher’s prostate gland was riddled with cancer, and a fairly aggressive version of it at that.

Gulcher is going in for surgery tomorrow, and not a moment too soon. Tests suggest that the disease has not yet spread to other parts of his body, a milestone that often portends death and that may well have been passed had he waited until he turned 50 to get a standard prostate-specific antigen (PSA) test.

Did genetic testing save Gulcher’s life? I think it may have. His dramatic story seems to illustrate perfectly the claims, made by his company and others, that an open market of DNA tests is the 21st century’s ticket to a healthier nation.

Link: Read the full article in the Washington Post.