Prevalence of Pathogenic Germline BRCA1/2 Variants and Their Association with Clinical Characteristics in Patients with Epithelial Ovarian Cancer in a Rural Area of Japan

Abstract

The prevalence of germline BRCA1 or BRCA2 pathogenic variants (gBRCA1/2-PV) in patients with primary epithelial ovarian cancer (OC) in a rural area of Japan and their association with clinical characteristics, including treatment response and survival outcome, were investigated. A total of 123 unbiased patients with OC were tested for gBRCA1 and gBRCA2 using next-generation sequencing-based targeted amplicon sequencing. Clinical characteristics of OC patients with and without gBRCA1/2 status were compared. The overall prevalence of gBRCA1/2-PV was 15.4% (19 cases), with gBRCA2-PV (10.5%, 13 cases) being more common than gBRCA1-PV (4.9%, 6 cases). Among the observed gBRCA1/2-PV, several novel variants were included, suggesting that gBRCA1/2-PV unique to the local area exist. gBRCA1/2-PV was significantly more prevalent in OC patients at an older age, with high-grade serous carcinoma, with advanced-stage tumors, and with a family history of breast cancer or hereditary breast and ovarian cancer syndrome (HBOC)-associated cancers. Patients with advanced-stage OC with gBRCA1/2-PV showed a significantly lower recurrence rate and tended to have better progression-free and overall survival than those with wild-type gBRCA1/2. Genetic testing for gBRCA1/2 status in all OC patients is useful not only for diagnosing HBOC in patients and their relatives to assess the risk of HBOC-associated cancers, but also to estimate therapy response and outcomes in patients.

Risk-reducing decisions regarding germlineBRCApathogenic variant: focusing on the timing of genetic testing and RRSO

“…Primary fallopian tube, peritoneal and ovarian carcinomas (OC) remain the most lethal gynaecological malignancy in women, 3 primarily because of their late-stage diagnosis, frequent recurrence and treatment resistance. 3 4 The prevalence of gBRCA1/2-PVs in a study of patients with OC was 11.7%-15.4%, [5][6][7] whereas the prevalence of gBRCA1/2-PVs among patients with OC of high-grade serous carcinoma in the Japanese population was reportedly 27.7%-29.7%, [5][6][7] a higher percentage than among Caucasians. 8 9 According to Japanese data, the age of the onset of OC was 51.3 10 and 55.8 11 years for gBRCA1 and 58.3 10 and 57.5 11 years for gBRCA2.…”