Correlation between the risk of ovarian cancer and BRCA recurrent pathogenic variants in Japan

We previously reported that L63X and Q934X are BRCA1 common founder variants in Japan. So far, there have been no reports of a correlation between such BRCA common variants and the risk of BRCA-related cancers. In this analysis, we investigated the correlation between the risk of ovarian cancer (OC) and BRCA recurrent pathogenic variants. We examined the database of the Japanese organization of hereditary breast and ovarian cancer. The database contained 3517 probands who underwent BRCA genetic testing. Among them, 11.1% (392/3517) had germline BRCA1 pathogenic variant, and 8.3% (293/3517) had BRCA2 pathogenic variant. We calculated the OC prevalence, breast cancer (BC) prevalence, and the ratio of OC to BC within second-degree relatives. The ratio of OC to BC in Q934X family members was significantly higher than that in the overall BRCA1 family members (0.80 vs.0.52: p = 0.038), and the ratio in STOP799 was 0.42, which was relatively lower than the overall BRCA1 value. Both Q934X and STOP799 are located in the ovarian cancer cluster region (OCCR), however there seems to be a difference in the risk of OC. R2318X family members had a significant higher ratio of OC to BC at 0.32 than the overall BRCA2 value of 0.13 (p = 0.012). R2318X is known to be located in the OCCR. This is the first report to investigate the correlation between BRCA recurrent variants and the risk of OC in Japan. The family members of probands with Q934X or R2318X have a higher risk of OC than that with other BRCA variants.