Difference in Risk of Breast and Ovarian Cancer According to Putative Functional Domain Regions in Korean BRCA1/2 Mutation Carriers

Abstract

IntroductionWe investigated the relative risk of breast and ovarian cancers related to the putative functional domain regions, obesity, and parity among Korean BRCA1/2 mutation carriers. Patients and MethodsWe analyzed the clinical characteristics, cancer history, and mutations according to the putative functional domain of BRCA proteins among 229 women with BRCA1/2 mutations who were treated at Yonsei Cancer Center, Severance Hospital between January 2009 and March 2017. ResultsTwenty-two carriers (18.8% of 117 BRCA1 mutation carriers) with mutations located in the BRCT domain region had a higher risk of breast cancers (hazard ratio [HR], 2.851; 95% confidence interval [CI], 1.614-5.039; P < .001) than those with mutations outside of the putative functional domains of BRCA1. The risk of ovarian cancer was increased in 13 (11.6%) of 112 BRCA2 mutation carriers, with mutations located on BRC repeat regions (HR, 3.129; 95% CI, 1.123-8.720; P = .029). The term-pregnancies number was a significant risk-reducing factor for breast cancers in BRCA1 mutation carriers (HR per pregnancy, 0.640; 95% CI, 0.508-0.806; P < .001), for breast cancers in BRCA2 mutation carriers (HR per pregnancy, 0.534; 95% CI, 0.419-0.681; P < .001), and for ovarian cancers for BRCA1 mutation carriers (HR per pregnancy, 0.625; 95% CI, 0.474-0.824; P = .001). ConclusionAmong Korean women with the BRCA1/2 mutation, the location of the mutations may influence the risk of breast and ovarian cancers according to the putative functional domain regions. Further investigations are required for risk prediction and preventive strategies in the BRCA1/2 mutation carriers.