Abstract
PURPOSETo provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management.METHODSWe used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment.RESULTSBRCA1 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. BRCA2 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 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers.CONCLUSIONIn 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.
Highlights
It is well established that pathogenic variants (PVs) in BRCA1 and BRCA2 (BRCA1/2) are associated with increased risks of breast and ovarian cancers in women for which reliable risk estimates are available.[1]
3,184 BRCA1 families and 2,157 BRCA2 families were informative for inclusion in the analysis, including 14,979 carriers, 9,296 noncarriers
BRCA1 PVs were associated with male breast (RR 5 4.30; 95% CI, 1.09 to 16.96), gallbladder (RR 5 3.34; 95% CI, 1.34 to 8.28), pancreatic
Summary
It is well established that pathogenic variants (PVs) in BRCA1 and BRCA2 (BRCA1/2) are associated with increased risks of breast and ovarian cancers in women for which reliable risk estimates are available.[1] Accumulated evidence indicates that BRCA1/2 PVs are associated with pancreatic cancer[2,3,4,5,6,7,8] and male breast cancer risks[3,6,9,10,11,12,13] and that BRCA2 PVs are associated with prostate cancer risk, aggressive prostate cancer, whereas the association between BRCA1. PVs and prostate cancer risk is still debated.[2,5,6,8,14,15,16,17]. The associations of pathogenic variants (PVs) in BRCA1 and BRCA2 with cancers other than female breast and ovarian cancers remain uncertain. Precise risk estimates are required to inform effective cancer risk management. This study investigates the associations between the risks of 22 cancers and BRCA1/2 PVs using data from 5,341 families segregating BRCA1 or BRCA2 PVs.
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