You Asked. Mary Answered.


By Mary Carpenter

The following is a new post in MyLittleBird’s Well-Being series “Answers to Readers’ Questions”:

Q: If I have a family history of cancer and heart disease, should I get genetic testing to figure out my personal risks (despite knowing I don’t have the BRCA variants signaling susceptibility to breast cancer)?

A:What most experts say: If there is anything you would be willing and able to do, such as more frequent screenings or changes in diet, to better protect yourself in the event that the results you get are “actionable”—then predictive genetic testing could be helpful.

Among commercially available and relatively inexpensive screening tests, the Color Extended test ($258.95) can analyze genes related to cardiac disease and medication response, as well as to eight types of cancer: breast, ovarian, uterine, colorectal, melanoma, pancreatic, stomach and prostate, according to the American Society of Clinical Oncology.  Such genetic screenings —also offered by 23 AND ME, Veritas and others — require an order from a physician, either one’s own or one provided by the company.

The risk of breast cancer rises from 13% of women in the general population to between 45 and 72% of women with a BRCA variant—who are expected to develop breast cancer by 70 to 80 years old. Also, in screenings of unselected populations, 50% of those discovered to have BRCA variants reported no personal or family history to indicate increased cancer risk.

Between 5% and 10% of all cancers might be related to inherited genetic mutations, with about 15% of colorectal cancers linked to a genetic profile called Lynch syndrome. For heart disease, the picture is more complicated, with interactions among various genes as well as lifestyle factors playing a greater role.

Critics have warned that “our ability to sequence DNA…has far outpaced our ability to understand how those genes cause cancer,” according to Wired. Said former UCSF researcher, “If you talk to docs, they say, ‘BRCA, that’s the only thing I’m interested in because I don’t know what to do with the other information.’” (Although that opinion dates from 2016, it remains widespread today.)

But according to the CDC, screening those populations with no family history is worthwhile for three conditions—Hereditary Breast and Ovarian Cancer Syndrome (cancers linked to the BRCA variants), Lynch Syndrome and Familial Hypercholesterolemia (very high cholesterol starting at an early age). For these three, there is sufficient evidence that interventions can reduce morbidity and mortality.

In results from an unselected population genetic-screening study for Mass General Brigham Biobank, “worrisome gene variants” found in 425 of 36,000 participants had “effects [that] could be ameliorated by…enhanced cancer surveillance or aggressive medical treatments to lower cholesterol, for example,” writes Gina Kolata in The New York Times.

One-third of the Biobank study participants contacted about their variants said they did not want to hear “what the gene was or what its effects might be.” But among those who did, at least one was grateful to learn he had Lynch syndrome —leading him to discover several relatives who had died from cancer, and to have screenings for liver and skin cancer as well as to begin annual colonoscopies.

While hereditary colon cancer has two forms—Lynch syndrome and another called polyposis— familial CRC (colorectal cancer) also occurs in “many other families” in which several members who have no apparent association with an identifiable genetic variant are diagnosed with colon cancer.

For breast and ovarian cancer, guidelines from the National Comprehensive Cancer Network (NCCN) updated in 2019 “still have a strong focus on BRCA1 and 2 mutations but also now include other high and moderate penetrance genes associated with breast, ovarian and pancreatic cancer,” according to NCCN Guidelines Panel Chair Mary B. Daly.  Penetrance refers to the likelihood that certain genes or gene variants will result in disease.

For heart conditions other than Familial Hypercholesteremia, genetic screening can also detect variants linked to cardiomyopathy (abnormality of the heart muscle), arrhythmia (abnormality of the heart rhythm) and arteriopathy (problems with the structures of arteries in the heart and other parts of the body). Finding the relevant genetic variants can motivate patients and healthcare providers to do more intensive or frequent monitoring for these conditions.

As genetic screening tests become more accessible, though, the issues involved remain complicated. One question relates to everyone who might be affected by one person’s genetic testing, such as other family members. Notes the American Cancer Society (ACS): “Not everyone might want to know if they are at increased risk.”  

Also, genetic testing can lead to additional medical tests, screenings and procedures — each potentially involving more stress and anxiety, as well as greater time and expense. The availability of insurance coverage raises questions about whether insurers or employers might use the resulting information to the detriment of the person being tested. According to the ACS, “Some people choose to pay for genetic testing themselves in order to keep the results as private as possible.”

For me, one parent had colon cancer but suffered so many other health problems that my risk is uncertain. As recommended, I’ve had regular colonoscopies since age 50, but I might schedule these more frequently if I knew I had a greater genetic risk. On the other hand, I remain unsure about whether I want to know and what I would do with that information.

—Mary Carpenter regularly reports on topical issues in health and medicine.

One thought on “You Asked. Mary Answered.

  1. Holly Pollinger says:

    Really informative. Thank you for putting all this in one place. I have just completed the 23&Me package and discovered a few things I may not have needed to know. But it does have me curious and so I may take the next steps. Haven’t made up my mind and I’m not sure there is room in there for any more information I’m supposed to take action on anyway.

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