BRCA1 & BRCA2: What Your Genetic Results Actually Mean

BRCA1 (chromosome 17) and BRCA2 (chromosome 13) are tumor suppressor genes. Their proteins repair double-strand DNA breaks through homologous recombination. When these genes carry pathogenic variants, DNA repair becomes impaired — allowing mutations to accumulate and increasing cancer risk.

It's important to understand: everyone has BRCA1 and BRCA2 genes. Having them is normal and essential. What matters is whether you carry a *pathogenic variant* (mutation) in these genes that impairs their function.

General population lifetime breast cancer risk: ~12% (1 in 8 women). With a BRCA1 pathogenic variant: 55–72% by age 80. With a BRCA2 pathogenic variant: 45–69% by age 80.

For ovarian cancer: general population risk is ~1.2%. BRCA1 carriers: 39–44%. BRCA2 carriers: 11–17%.

Male breast cancer risk also increases: general population ~0.1%, BRCA2 carriers ~6–8%. Prostate cancer risk is elevated in BRCA2 carriers as well.

Key point: these are *lifetime cumulative risks*, not guarantees. Many carriers never develop cancer, especially with proactive surveillance and risk-reduction strategies.

23andMe tests for exactly 3 BRCA variants — three specific Ashkenazi Jewish founder mutations (185delAG and 5382insC in BRCA1, 6174delT in BRCA2). These three variants account for ~90% of BRCA mutations in Ashkenazi Jewish individuals but only ~2% of all known BRCA pathogenic variants.

GenomeInsight analyzes the SNPs available on consumer arrays, but we are not a diagnostic test. A negative result on consumer genotyping does NOT rule out a BRCA mutation. There are over 1,800 known pathogenic BRCA variants, and most require clinical-grade sequencing (not array genotyping) to detect.

If you have a strong family history of breast or ovarian cancer, talk to a genetic counselor about clinical BRCA testing regardless of consumer test results.

NCCN guidelines recommend genetic counseling and possible testing if you have:

• Breast cancer diagnosed before age 50 • Triple-negative breast cancer before age 60 • Two or more primary breast cancers • Male breast cancer at any age • Ovarian, fallopian tube, or peritoneal cancer at any age • Known BRCA mutation in the family • Ashkenazi Jewish ancestry with any breast/ovarian cancer • Pancreatic cancer with 2+ close relatives with BRCA-associated cancers

Genetic counseling costs are typically covered by insurance when clinical criteria are met.

Enhanced Surveillance: • Annual mammogram + breast MRI starting at age 25–30 (alternating every 6 months) • Clinical breast exam every 6 months • Transvaginal ultrasound + CA-125 every 6 months for ovarian surveillance (though sensitivity is limited)

Risk-Reducing Surgery: • Bilateral risk-reducing mastectomy reduces breast cancer risk by ~90% • Risk-reducing salpingo-oophorectomy (RRSO) reduces ovarian cancer risk by ~80% and breast cancer risk by ~50% if done before menopause

Chemoprevention: • Tamoxifen or raloxifene can reduce breast cancer risk by ~50% in high-risk women • Olaparib (PARP inhibitor) is FDA-approved for treatment of BRCA-associated cancers

The right strategy depends on your specific variant, family history, age, and personal preferences. These decisions should always involve a multidisciplinary medical team.

In 2013, Angelina Jolie publicly disclosed her BRCA1 pathogenic variant and decision to undergo preventive double mastectomy. Studies showed this increased BRCA testing rates by 64% (the 'Angelina Jolie effect'). Importantly, it also increased *appropriate* testing — more women with legitimate risk factors sought counseling.

Jolie's transparency helped normalize genetic testing and proactive health management. However, it also created misconceptions — many women without risk factors sought unnecessary testing, and some overestimated what consumer DNA tests can detect.