Cancer risks associated with BRCA1 and BRCA2 pathogenic variants

Abstract

PURPOSE To provide precise age-specific risk estimates of cancers other than female breast and ovary associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management. METHODS We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment. RESULTS BRCA1 PVs were associated with risks of male breast (RR=4.30; 95% confidence interval (CI), 1.09-16.96), pancreatic (RR=2.36; 95% CI, 1.51-3.68) and stomach (RR=2.17; 95% CI, 1.25-3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR=44.0; 95% CI, 21.3-90.9), stomach (RR=3.69; 95% CI, 2.40-5.67), pancreatic (RR=3.34; 95% CI, 2.21-5.06) and prostate (RR=2.22; 95% CI, 1.63-3.03) cancers. The stomach cancer RR was higher for females than males (6.89 vs 2.76; P=0.04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to ~2.5% for pancreatic cancer for BRCA1 carriers, and from ~2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers. CONCLUSION In addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.