Cancer Risks Associated With <i>BRCA1</i> and <i>BRCA2</i> Pathogenic Variants.

Abstract

To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in <i>BRCA1</i> and <i>BRCA2</i> for effective cancer risk management. We used data from 3,184 <i>BRCA1</i> and 2,157 <i>BRCA2</i> families in the Consortium of Investigators of Modifiers of <i>BRCA1/2</i> to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment. <i>BRCA1</i> PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. <i>BRCA2</i> PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 <i>v</i> 2.76; <i>P</i> = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for <i>BRCA1</i> carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for <i>BRCA2</i> carriers. In addition to female breast and ovarian cancers, <i>BRCA1</i> and <i>BRCA2</i> PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only <i>BRCA2</i> 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 <i>BRCA1/2</i> PVs.