My Journey From DNA Test Skeptic to Participant

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Not so many months ago, I wrote a post about the “Wild West Marketplace” of consumer genetic testing. That description came from Laura Hercher, a highly respected genetics counselor whom I interviewed for the piece. Though our focus primarily was on the entertainment aspect of consumer DNA testing (tracing one’s ancestry, etc.), we also discussed the more serious health implications. I find the topic fascinating, but I thought I’d leave it there. Hercher pointed out many of the flaws and potentially false results that these tests may yield.

Then events made me take a second look at the feasibility of genetic testing in my own life: my sister died of pancreatic cancer, only 43 days after she’d been diagnosed. (Despite our grief, in view of the horror of this disease, we all realized that the brief time period was a blessing). Knowing that my mother had had bilateral mastectomies for breast cancer, and that her mother had died in her 50s from what we thought was liver cancer but could have been a metastasis from breast or other site, I began to think about my likelihood of developing a heritable cancer. 

And—even more to the point—I thought about my daughters. My gynecologist had told me years ago that I owed it to my daughters to find out if I carried variants in the BRCA1 and/or BRCA2 genes, which are associated with cancers of the breast and ovaries and—it turns out—pancreas as well. At the time, genetic testing cost more than $5000, so I never followed up on her recommendation. It’s worth noting here that the preponderance of women who develop breast cancer have no known risk factors.

As a former health writer/editor and continuing catastrophizer, I immediately felt I needed more information about pancreatic cancer. The heritable component ranges from 5% to 10%. But I knew that unlike some cancers, which are now being regarded as chronic diseases, pancreatic cancer carries a prognosis that is usually dire. The American Cancer Society reports that pancreatic cancer accounts for about 3% of all cancers in the US—and about 7% of all cancer deaths. That high mortality rate is because it’s nearly always diagnosed late, after it has metastasized. 

But I wondered: if I tested positive for the pancreatic cancer variant, were there any monitoring programs that might make it possible to find the disease at an earlier stage? And were there medical genetic tests that were more reliable than some of the “consumer DNA” ones that Hercher had discussed?

My research led me to Johns Hopkins, one of the medical centers doing considerable work in this field, and they did, indeed, have a surveillance study for those who’d tested positive for heritable pancreatic cancer. Knowing that gave me a sense of control in the midst of my personal concerns and while my sadness at the sudden loss of my sister was still quite raw. The people I spoke with there suggested that I have heredity genetic cancer screening done—and they recommended as a reliable company Color Genomics.

I contacted Laura Hercher, told her about my sister’s death and my family history, and sought her advice. She and a friend/colleague who specializes in cancer counseling agreed that my family history of breast cancer merited testing and was more likely to be associated with a positive test result than the pancreatic cancer: “likelihood of a positive test result there is 10% times 1/2, since there is a 50% chance you share any gene your sister had—but I would say less than that because the cancer occurred over a certain age.”

But she also included a link to an article suggesting that every pancreatic cancer patient should consider genetic testing. Although she had been skeptical about pancreatic cancer screening because there’s no proven way to do it, this article suggested that screening may be effective for both patients and families.

However, she added a caveat: “Understand that our track record with screening for cancer is pretty dismal. Many things that sounded great on paper didn’t result in fewer deaths…but still worth considering.”

She recommended Color Genomics, the same company that Johns Hopkins had suggested, so I felt confident with those dual recommendations from trusted sources. I’m not suggesting they are the only reputable firm, of course.  A friend who works in cancer education for oncologists said she’d heard positive things about Invitae, and I’m sure there are others as well. 

I encourage anyone who is considering this action to do some research and talk with medical sources you trust.

I spoke with my physicians. My primary care physician was skeptical, asking me to think through what I’d do with the results. Both my gynecologist and gastroenterologist thought testing was a good idea in my circumstances and offered to write the medical requests necessary to get the test (more on this shortly). My gynecologist said that although many of her patients who test positive for these mutations opt to have their ovaries removed, if I chose not to do so, I could have half-yearly ultrasounds and Ca-125 blood work, which indicates the presence of cancer.

I also had intense interest in joining a pancreatic cancer surveillance study—for myself and my family, as well as to add to scientific understanding of the disease that took my sister’s life and is occurring with greater frequency.

But I had to think long and hard about my mental mindset. Which way would I worry more—if I had the test and received positive results, or if I didn’t have the test and was left to wonder? Of course, as Hercher had stressed in my interview with her, and we all should keep in mind: testing positive for a cancerous genetic mutation does not necessarily mean an individual will get that cancer, and testing negative doesn’t mean that individual won’t. We’re advancing our knowledge of genetics all the time, but so many other variables may play a role in specific cancers—diet, lifestyle issues, environmental aspects, and plain dumb luck among them. 

I also did some due diligence: checking resources from the American Cancer Society, the U.S. National Library of Medicine, and the National Cancer Institute. The latter carried this caveat about using Direct to Consumer (DTC) genetic tests:

“Even when people have DTC genetic tests for gene variants that are known to be associated with inherited cancer susceptibility syndromes, there are potential risks and drawbacks to the use of DTC testing. For instance, some DTC genetic tests look for variants in the BRCA1 and BRCA2 genes that are associated with Hereditary Breast and Ovarian Cancer Syndrome (HBOC). However, this testing looks only for three specific variants out of the thousands that have been identified. Therefore, someone could have a negative result with this kind of test but still have a harmful BRCA1 or BRCA2 gene variant that was just not identified by that test. In particular, without guidance about the most appropriate genetic testing to do and interpretation of the genetic test results from a knowledgeable health care provider, people may experience unneeded anxiety or false reassurance, or they may make important decisions about medical treatment or care based on incomplete information.”

This is an important reminder that if you opt for inherited cancer genetic testing, you must be cautious about the source you select.

Ultimately, I couldn’t get past the idea that if I didn’t get tested, I wasn’t doing everything I could to protect my daughters. What they did with the information would be their decision, but I felt I needed to get it for them.

I bought the Color Heredity Cancer Test from Amazon for less than $200. It tested for 30 known gene mutations associated with breast, ovarian, pancreatic, stomach, colorectal, and uterine cancers, and melanoma. 

Here’s where the doctor issue arose. My physicians were right that a doctor’s authorization was needed, though that information wasn’t provided on Amazon or on the Color site—until I registered to proceed. Then I was told that I needed my doctor’s approval. Color company representatives were accessible by phone and said that since I didn’t have that approval, one of their doctors would review my personal and family history and the final results at no extra fee.  I also knew a genetic counselor would be available for me to talk with once I received my results.

It was time to act. After reading the directions not to eat, drink (even water), smoke, or chew gum for 30 minutes before providing the saliva sample, I followed the three simple steps as described: 1) Activate your kit online; 2) Provide your saliva sample [tube included, and a clear video available to answer any questions]; 3) Return kit via the US Postal Service. 

I was promised results within four weeks. I then did an amazing thing for a catastrophizer: I put all thoughts of the test and its implications out of my mind and didn’t agonize at all.

Two weeks later, an email arrived informing me that my test results were attached. I felt fortunate that the timetable was earlier than stated: I didn’t have time to anticipate the arrival.

I took a few deep, cleansing breaths, relaxed my tense shoulders, and opened the email.

I had tested negative for all 30 genetic variants. 

I breathed deeply again—this time with considerable relief—read all the disclaimers (which I knew: results meant no guarantees one way or the other), and decided that I’d avail myself of the talk with the genetic counselor just to see whether there was additional information I could learn. 

The woman I spoke with said my findings “didn’t give us much insight.” There was a possibility, she said, that my mother had a genetic mutation that I didn’t inherit—or a gene that hasn’t yet been identified as playing a role in these diseases. 

And she observed that since new genetic information is becoming available all the time, it’s probably a good idea to be tested every two to five years. That recommendation struck me as having a bit of a marketing tinge. 

As far as I can see, I’m done now. I’m grateful for the results, which mean I won’t have to worry about what I might have passed along to my daughters in this regard. And I won’t need extra monitoring myself—or to enter into a pancreatic cancer surveillance program.

Time to remind myself of mindfulness meditation: not to regret the past or worry about the future—just savor the present, each and every minute of it.

How does all of this strike you? Aside from ancestry testing, if you know you have a family history of cancer, have you, would you, will you consider cancer heredity genetic testing for future medical issues?  If so, under what circumstances? (I certainly understand the thinking of those who choose not to know.)  Your insights, opinions, and stories are, as always, most welcome.

Annie

 

Navigating “The Wild West” Marketplace of Consumer Genetic Testing–and Other Needed Information About Our DNA

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In an article in The New York Times Sunday Review, genetics counselor Laura Hercher described a man named Matthew Fender, who—after searching for heredity data through 23andMe—had placed his genetic test results into Promethease, a DNA search engine that probes such data for variants cited in the medical literature. 

Fender had sought to learn his risk for developing a pulmonary embolism, the condition that had killed his sister, a seemingly healthy young woman of 23. The report didn’t mention that, but it did provide the alarming news that he carried a mutation (PSEN1) strongly associated with early onset Alzheimer’s, as well as two copies of a gene variant (ApoE4) that indicates greatly increased chances of developing late-onset Alzheimer’s.

After getting no satisfactory guidance from his primary care doctor and other professionals, Fender checked out a competing genetics company, Ancestry DNA,  to see what his results there would say about the PSEN1 variant. They said nothing. He then persuaded his doctor to order the test, which proved negative.

End of story for Fender, although he said the experience led him to improve his diet and to consider using his technological skills to develop an app to assist people with dementia through voice-activated devices such as Siri and Alexa.

It’s worth noting that both companies claimed their tests were 99.9% accurate. Yet a 23andMe representative told Hercher that “a 99.9% accuracy can still mean errors.” And apparently, not every variant in their chip is even validated for 99.9% accuracy.

“The direct-to-consumer genetic testing marketplace is a regulatory Wild West,” wrote Hercher, who is the director of research at the Sarah Lawrence College Graduate Program in Human Genetics.

She’s also the host of an informative and entertaining podcast, “The Beagle Has Landed,” (named after Charles Darwin’s ship—not Charles Schulz’s Snoopy), designed for both professionals and “curious patients,” according to its introductory press release. One of her interviewees was Matt Fender.

Hercher explained that FDA Commissioner Scott Gottlieb announced in November a new regulatory approach that will allow companies like 23andMe to market some tests to determine health risks without premarket review. That change, Hercher observes, “is expected to usher in a rapid expansion of the consumer genetics industry.”

That means we consumers will need to better prepare ourselves to function in this new ”Wild West” by getting a better education on the important topic of genetics and the role it plays in our health—even as the field itself is changing all the time.

With that backdrop,  I spoke with Hercher to elicit her opinions on how to view all these genetic data at this stage. 

First, to her, the quest for information about one’s heritage, which she calls the “ancestry craze,” is a “mixed bag.” The positives she underscores are that people enjoy and are intrigued by learning about their forebears, and the process brings science and genetics into people’s lives.

But when people ask her if these quests yield legitimate information, she responds: “It’s accurate-ish. People think of this as their genealogy, but once you get past Mom and Dad, there’s a lot of randomness—you could inherit something important, or not.”

“People like to tell a story they can understand, a narrative that can explain why people turned out certain ways. Genetics also tells a story, but the risk we run is that when hearing it, we put aside other stories—involving culture and heritage, for example.  It’s very hard to weave it all together.”

If we’re interested in our predecessors’ story, then their story is ours, she notes, and that’s valuable to us. “Genes are a part of that, but not all of it. Even among siblings: one person could have 34% Southern European heritage, while his brother registered 15%. Would that make sense? No. The tests don’t gather with that level of precision.”

Hercher analogizes a swimming pool, with some blue substance for African ancestry, red for Chinese, etc. “The testers scoop a sampling from a spot of genomes into a net, and they’ll get red, green, yellow,” she says.  “Different tests reach down and get the same mix, but it’s not identical.”

To Hercher, the ancestry tests also tend to encourage a kind of tribal thinking and ignore the overriding message: 99% of our DNA identifies us as human and is genetically shared among us. “The DNA story is our commonality as a people—as well as with other living things. I wish these companies presented the data in a way that made that clear.”

And this commonality has great implications for the subject of race. “No quality geneticist will tell you that the concept of race does a good job of describing our shared genetic ancestry. Race isn’t a scientific grouping; it’s defined culturally. There’s more mixture within groups than between groups.” In a point that is probably obvious to all but the most rabid white supremacists, she says: “Racial purity is a myth.”

Those in the genetics field are disturbed by the current efforts to bring back eugenics, or “scientific racism,” which was once believed even by serious scientists who felt they could, by controlled breeding, create an increase in desirable heritable traits and a decrease in undesirable ones, thereby improving the human race. 

The concept was easily manipulated and became discredited after its use by the Nazis in Germany. “Now all these things are widely talked about,” Hercher laments. “The white nationalist movement has adopted the language of hate ideology and put a scientific gloss on it.”

This is the background for the hot water that Massachusetts Senator Elizabeth Warren has gotten herself into by taking a DNA test to prove her Native American ancestry. With this action, critics say, the possible 2020 Presidential candidate has played into the concept of “racial science”–validating the alleged link between blood and race, which The New York Times calls “a bedrock principle for white supremacists and others who believe in racial hierarchies.”

That’s not, I trust, the way most of us view genetics. We may remember how we were introduced to the subject in school: with Gregor Mendel and the 29,000 pea plants he cultivated that formed the foundation of the field. But even among the experts, “we never knew how complicated heredity is,” Hercher says. Single gene inheritance, such as blood type, is fairly straightforward and rare—as are diseases attributed to a single gene, the so-called “Mendelian diseases,” which include sickle cell disease, as well as cystic fibrosis, Huntington disease, muscular dystrophy, and a few others. 

Most of genetics, Hercher stresses, is more multi-layered. Heredity, and the traits and illnesses that are in our DNA, involve the interaction of genes with both our external environment and the internal environment comprised of our hormones, metabolism, and other factors. So when we find out we have certain genes—and their variants and mutations—there’s no straight line to determining how our bodies will deal with their existence.

One important issue that stirs debates among geneticists involves ApoE4—the gene that denotes a higher risk for Alzheimer’s and carries both individual and societal implications—for care and economics—as our population ages. Approximately 25% of Caucasians carry this gene, but Hercher points out that an individual at somewhat increased risk may not develop the disease; while someone with decreased risk may still get it. 

And currently, without a cure, that raises questions. “There’s a faction in the genetics counseling community that says we have no business giving out that information,” says Hercher. Indeed, when Matt Fender initially sought guidance from his primary care doctor, Hercher reported in her Times article, the doctor responded: “What the heck do we do about it, once we know, other than create high anxiety?” However, says Hercher, “a growing faction says that whether or not to provide the information is not really our call.” In other words, it’s the patient’s decision.

So if we’re deciding to search out our ancestry–or to be tested for a possible disease– the important thing for us, the consumer/patient, is to seek education before we even consider being tested. 

How will we regard the potential results? Do we need the information to inform our choices about health decisions that must be made—before a pregnancy, for example, or to assess our odds of developing certain cancers?

On such matters, Hercher stresses, both factions in the genetics counseling community agree: if the information is to be given, good counseling should be involved to help patients think through the implications—and then to support them once they’ve decided whether or not to act on the findings.

What do you think? Have you had any experiences you’d like to share? Please enter them in the Comment box near the bottom of this post.

Annie

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