Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants
Authors: Li Shuai , Silvestri Valentina , Leslie Goska , Rebbeck Timothy R. , Neuhausen Susan L. , Hopper John L. , Nielsen Henriette Roed , Lee Andrew , Yang Xin , McGuffog Lesley , Parsons Michael T. , Andrulis Irene L. , Arnold Norbert , Belotti Muriel , Borg Åke , Buecher Bruno , Buys Saundra S. , Caputo Sandrine M. , Chung Wendy K. , Colas Chrystelle , Colonna Sarah V. , Cook Jackie , Daly Mary B. , de la Hoya Miguel , de Pauw Antoine , Delhomelle Hélène , Eason Jacqueline , Engel Christoph , Evans D. Gareth , Faust Ulrike , Fehm Tanja N. , Fostira Florentia , Fountzilas George , Frone Megan , Garcia-Barberan Vanesa , Garre Pilar , Gauthier-Villars Marion , Gehrig Andrea , Glendon Gord , Goldgar David E. , Golmard Lisa , Greene Mark H. , Hahnen Eric , Hamann Ute , Hanson Helen , Hassan Tiara , Hentschel Julia , Horvath Judit , Izatt Louise , Janavicius Ramunas , Jiao Yue , John Esther M. , Karlan Beth Y. , Kim Sung-Won , Konstantopoulou Irene , Kwong Ava , Laugé Anthony , Lee Jong Won , Lesueur Fabienne , Mebirouk Noura , Meindl Alfons , Mouret-Fourme Emmanuelle , Musgrave Hannah , Ngeow Yuen Yie Joanne , Niederacher Dieter , Park Sue K. , Pedersen Inge Sokilde , Ramser Juliane , Ramus Susan J. , Rantala Johanna , Rashid Muhammad U. , Reichl Florian , Ritter Julia , Rump Andreas , Santamariña Marta , Saule Claire , Schmidt Gunnar , Schmutzler Rita K. , Senter Leigha , Shariff Saba , Singer Christian F. , Southey Melissa C. , Stoppa-Lyonnet Dominique , Sutter Christian , Tan Yen , Teo Soo Hwang , Terry Mary Beth , Thomassen Mads , Tischkowitz Marc , Toland Amanda E. , Torres Diana , Vega Ana , Wagner Sebastian A. , Wang-Gohrke Shan , Wappenschmidt Barbara , Weber Bernhard H. F. , Yannoukakos Drakoulis , Spurdle Amanda B. , Easton Douglas F. , Chenevix-Trench Georgia , Ottini Laura , Antoniou Antonis C. 
Published: January 2022

PURPOSE To 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. METHODS We 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. RESULTS BRCA1 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. 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.