In a study reported in the Journal of Clinical Oncology, Li et al found that pathogenic variants in BRCA1 or BRCA2—recognized risk factors for female breast and ovarian cancers—were also associated with increased risks of male breast, pancreatic, stomach, colorectal, gallbladder, and prostate cancers.
Study Details
The study used data from 3,184 BRCA1 and 2,157 BRCA2 families from 26 study groups in the Consortium of Investigators of Modifiers of BRCA1/2. Age-specific and overall risks were estimated for 22 first primary cancer types, excluding female breast and ovarian cancers. Cancer incidence among pathogenic variant carriers was compared with age-, country-, and birth cohort–specific population incidence.
Key Findings
BRCA1 pathogenic variants were associated with significantly increased risk of male breast (relative risk [RR] = 4.30, 95% confidence interval [CI] = 1.09–16.96), gallbladder (RR = 3.34, 95% CI = 1.34–8.28), pancreatic (RR = 2.36, 95% CI = 1.51–3.68), stomach (RR = 2.17, 95% CI = 1.25–3.77), and colorectal (RR = 1.48, 95% CI = 1.01–2.16) cancers. No association was found for prostate cancer (RR = 0.82, 95% CI = 0.54–1.27) or any other evaluated cancer. No significant differences between sexes was observed; a borderline higher risk for stomach cancer was observed for women vs men (RRs = 4.86 vs 1.67, P = .08 for interaction).
In addition to female breast and ovarian cancers, BRCA1 and BRCA2 pathogenic variants are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 pathogenic variants) 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 pathogenic variants.— Li et al
Tweet this quote
BRCA2 pathogenic variants were associated with significantly increased risk 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. A borderline increased risk was observed for eye cancers (RR = 4.60, 1.00–21.16). No other significant associations were observed. The risk ratio for stomach cancer was greater for women vs men (6.89 vs 2.76, P = .04 for interaction); no other significant between-sex differences were observed.
Among BRCA1 pathogenic variant carriers, absolute risks by age 60 and 80 years were: 0.07% and 0.4% for male breast cancer; 0.3% and 2.3% for women and 0.4% and 2.9% for men for pancreatic cancer; and 0.3% and 0.7% for women and 0.6% and 1.6% for men for stomach cancer.
Among BRCA2 pathogenic variant carriers, absolute risks by age 60 and 80 years were: 0.7% and 3.8% for male breast cancer; 2.9% and 26.9% for prostate cancer; 0.6% and 2.3% for women and 0.9% and 3.0% for men for pancreatic cancer; and 0.6% and 3.5% for women and 0.5% and 3.5% for men for stomach cancer.
As noted by the investigators, other data have suggested increased risks of cervical, corpus uterine, kidney, and testicular cancers for BRCA1 pathogenic variants and increased risk of bone, brain, blood, and gallbladder cancers and melanoma for BRCA2 pathogenic variants. The current analysis did not confirm such increased risks.
The investigators concluded, “In addition to female breast and ovarian cancers, BRCA1 and BRCA2 pathogenic variants are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 pathogenic variants) 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 pathogenic variants.”
Antonis C. Antoniou, PhD, of the Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Cancer Research UK, Gray Foundation, Fondazione Associazione Italiana Ricerca sul Cancro, and others. For full disclosures of the study authors, visit ascopubs.org.
