A genetic variant is a permanent change in the DNA sequence that makes up a gene. While genetic variants often result in genetic disorders associated with poor health, some variants can be benign or even beneficial health. Pathogenic variants (PVs), also called mutations, describe variants responsible for causing diseases. PVs are defined based on significant scientific research supporting the association between genetic mutation and a specific disease.
Researchers have extensively studied BRCA1 and BRCA2 since their discovery in 1990 and 1994, respectively. Identifying PVs in BRCA1/2 genes has led to an understanding of their well-documented role in breast and ovarian cancers in women. BRACA1/2 genes are inherited from our parents, and we receive one copy of each gene from our mother and one copy from our father, so everyone has two copies of each. Normal copies of BRCA1/2 produce proteins that help repair DNA damage. Thus, inheriting a mutant copy of either of these genes increases cancer risk.
Approximately 1 in 500 women in the United States have a mutation in their BRCA1 or BRCA2 gene. Accurate risk estimates help shape cancer screening and prevention strategies. Further, identifying individuals at increased risk of developing cancer due to BRAC1/2 PVs enhances the ability to provide genetic counseling to those at greatest risk. The plethora of research on PVs in these genes has led to significant outreach to encourage genetic screening for women with a family history of BRCA-related cancers. There has been a longtime focus on understanding how these mutations could influence other types of cancer.
Researchers have linked BRCA mutations and other cancers, including male breast, prostate, colon, and pancreatic cancers. However, the studies published on these cancer types tended to have low sample sizes resulting in imprecise risk estimates. Until now, scientific literature has lacked precise risk estimates for PVs leading to cancers other than female breast and ovarian cancer. A recent study published in the Journal of Clinical Oncology has provided age-specific risk estimates for PVs of BRAC1/2 in male breast, prostate, stomach, and pancreatic cancers.
The study analyzed data from the Consortium of Investigators of Modifying BRCA1/2 (CIMBA). Researchers generated a dataset containing information from over 3,000 and 2,000 families having at least one family member carrying a BRCA1 or BRCA2 mutation to identify associations between BRCA1/2 PVs and 22 different cancers.
The researchers uncovered numerous cancers with elevated risk for BRCA1/2 carriers. The study found that BRCA1 PVs increased the risk of male breast, pancreatic, and stomach cancers. The study also demonstrated associations between BRCA2 PVs and male breast, stomach, pancreatic, and prostate cancers. Notably, men with a BRCA2 mutation had a nearly 27% risk of developing prostate cancer by age 80 and over 33% by age 85.
The authors conclude that BRCA1/2 PVs increase the risk of cancers which male breast, pancreatic, stomach, and prostate cancer. The manuscript provides estimated age-specific risks that oncologists and physicians can use to improve cancer risk management for men and women with a BRCA1/2 mutation.