BRCA germline mutations in an unselected nationwide cohort of Chinese patients with ovarian cancer and healthy controls

Abstract Objective To investigate the BRCA status in Chinese patients with ovarian cancer (OC). Though there were two large prevalence studies in Chinese OC patients, this was the first time to observe it in healthy controls. Methods We performed BRCA mutation screening using next-generation sequencing to determine the prevalence of BRCA germline deleterious mutations in an unselected cohort of Chinese OC patients (n = 1331) versus healthy controls (n = 1763) and describe the types and spectrum of BRCA deleterious variants. Results Among the 1331 patients with OC, 227 (17.1%) carried deleterious variants in BRCA 1 and 70 (5.3%) carried deleterious variants in BRCA 2. Of 1763 control subjects, 6 (0.3%) and 2 (0.1%) had deleterious variants in BRCA 1 and BRCA 2. No patient carried mutations in both BRCA 1 and BRCA 2 simultaneously. Sixty-three novel mutations were identified, and three Chinese specific hot-spot mutations were notified as BRCA 1 c.5470_5477delATTGGGCA, BRCA 1 c.981_982delAT, and BRCA 1 c.3770_3771delAG. Interestingly, all these high-frequency recurrent mutations were distributed on exon 10, which may also be the Chinese OC BRCA mutations' distinct characteristics. In addition, in our study, the estimated odds ratio (OR) of OC associated with BRCA 1 positive variants were approximately 34.6 (95% CI, 12.5–95.7) in age group under 40 and 42.4 (95% CI, 5.9–305.2) in group older than 50 in the Chinese population, respectively. Conclusions We recommend BRCA testing to all Chinese OC patients and those general Chinese who have family members with hereditary breast and ovarian related cancer (HBOC)-related cancers. Variants carriers would not only benefit from early prevention of OC but also for the medical management.