Learning about my genetic mutation (BRCA2), and optimism for the future of health research
Last month, I decided to try Color — one of several new personal genetic sequencing tools. Color screens for genetic mutations associated with various cancers and other diseases. As a health data geek, and as a patient with a family history of cancer, I was curious to understand more about my genetic makeup and understand my own risk profile.
This post will walk through the testing, the results, and the known implications, and how it informs my view on the future of health research.
My Process & Results
The Color experience was extremely seamless: they mailed me a kit; I provided a saliva sample and mailed it back to them. A few weeks later, they reached out to schedule a phone appointment with a genetic counselor to review my results.
I discovered that I have a BRCA2 mutation, one of the most significant (known) mutations impacting the risk of cancer. The BRCA2 mutation impacts about 1 in 245 Americans, and is associated with increased risk of a variety of cancers. It is most notable for its impact on women: while the typical woman has a ~12% lifetime risk of breast cancer, women with BRCA mutations have ~70% risk, including much younger diagnoses on average. There are similarly dramatic effects on the incidence of ovarian cancer for women with BRCA mutations. While every case is different and it is a deeply personal decision, some women with BRCA mutations facing these statistics may choose to take preventive measures, including choices like preventive mastectomies. BRCA mutations are among the most well-known mutations that exist, with public figures like Angelina Jolie and Christina Applegate having shared their experiences.
Relative to women, the impact on men is less significant, but is still meaningful. In addition to being a carrier, men face their own risks. The average US male has a ~10% lifetime risk of prostate cancer; patients with BRCA mutations have 17–34% odds of prostate cancer. While breast cancer is extremely rare for men without the BRCA mutation (<0.1% prevalence), 5–10% of men with BRCA mutations are diagnosed with breast cancer (and men with BRCA mutations are recommended for similar self-exam and annual breast exam procedures as women). Incidence of melanoma and pancreatic cancer is also significantly higher for males with BRCA mutation than the general population. And significantly, as a carrier, any children I have will each have 50% odds of also having the mutation.
For males, there is less immediate action to take after discovering a BRCA mutation, so one question I considered upfront was whether the knowledge was valuable. That said, there are actionable steps for males: patients can set up a personalized risk reduction plan that establishes cancer screenings and makes healthy lifestyle recommendations. I made the choice to be tested with eyes wide open; before I took the test, I already knew that my mother had a BRCA mutation (she is a breast cancer survivor), so there would be 50–50 odds for myself. I decided the incremental knowledge was valuable, and that I would rather have the knowledge to optimize my choices over time. This is also a deeply personal choice for people to make, and for myself I am glad consumer genetic screening tools like this exist (and I also appreciated the role of the genetic counselor in explaining the results).
Why My Results Make Me More Optimistic about the Future of Medical Research
Going through the process of genetic screening, I am fortunate in many respects. For this circumstance, I am fortunate to be male, where the impacts of a BRCA2 mutation are smaller (though still very significant). I am fortunate to be young enough that there is a reasonable likelihood that these cancers may have treatments by the age they are most likely to impact me (and an even higher likelihood that any children I have would have cures).
One subtle form of luck is that I’m fortunate that I have a mutation that is known to be problematic. The first BRCA gene was not isolated until 1994, and most problematic mutations that exist in the human genome aren’t understood or even identified.
The history of BRCA gene discovery is a triumph in the power of health data and correlative research. As The Gene recounts, the search for breast cancer-causing genes began in the 1970s with a brave geneticist named Mary-Claire King. King hypothesized that breast cancer was genetic, and when the National Cancer Institute launched a survey for breast cancer patients, she added questions about family history. A pattern quickly emerged, but the search for the BRCA gene took more than a decade. Researchers raced to identify the gene, and ultimately Myriad Genetics isolated the BRCA1 gene in 1994 (one year before they isolated the BRCA2 gene).
King is a pioneer and the discovery of BRCA was a triumph, but today we no longer have to settle for a 15 year search to locate disease-causing genes. DNA sequencing was only invented as King was commencing her research in the late 1970s, and the Human Genome Project was not completed until 2003 — at a cost of $3 billion. Today, as the cost of sequencing continues to drop (whole genome sequencing is now available for less than $1000!), it is much more feasible to link genetic data with clinical outcomes and allow researchers to more rapidly identify disease-causing genetic mutations.
This is especially important because the problem has become exponentially complex: many diseases aren’t just associated with one gene, but instead are associated with complex combinations of genetic and other factors — so the combinatorics and amount of data required to isolate genetic causes becomes much greater. For progress to accelerate, new sequencing technology is not enough. Society also needs:
- A critical mass of patients sequenced (preferably with whole genome sequencing). This should become more probable as sequencing gets cheaper and cheaper.
- A solution to the giant collective action problem of data use rights and patient privacy — enabling data to be unlocked at scale for research purposes while patients control access and benefit from its use
- A robust, interoperable data ecosystem that makes it easy to connect clinical outcomes with genetic data
If we succeed, then within a generation, actionable genomic information will be integrated into the ordinary course of care, allowing patients and their physicians a much more complete and personal understanding of their health — and hopefully better treatments that come from this knowledge. Isolating BRCA1/2 and making it easier for patients to discover their mutations and take steps to reduce their risk of cancer has been a triumph in medical research, and hopefully foreshadows a future of personalized care.
Appendix: Resources for the BRCA Patient Community
Facing Our Risk of Cancer Empowered (FORCE) — a national non-profit organization dedicated to improving the lives of individuals and families affected by hereditary breast, ovarian, and related cancers.
Basser Center for BRCA (Penn Medicine) — the first comprehensive center for research, treatment and prevention of BRCA-related cancers
Bright Pink — national non-profit organization focused on the prevention and early detection of breast and ovarian cancer in young women
UCSF — Center for BRCA Research — to provide a central resource for families with BRCA and other mutations to receive personalized care and planning for their long-term health and well-being. This is our opportunity to rethink how we treat and manage hereditary cancers.
National Ovarian Cancer Coalition (NOCC) — The mission of the NOCC is to fight tirelessly to prevent and cure ovarian cancer and to improve the quality of life for survivors. The NOCC offers many ways to connect through its Web site and social media channels.
Ovarian Cancer Research Fund Alliance (OCRFA) — OCRFA is a powerful voice for everyone touched by ovarian cancer. This organization connects survivors, women at risk, caregivers, and health care providers with the resources they need, and funds scientific research.
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