Germline BRCA1 and BRCA2 variants in a population based cohort of ovarian, peritoneal or fallopian tube cancer patients in Malaysia

Abstract

Background : Germline BRCA1 or BRCA2 pathogenic variants in ovarian cancer patients may be predictive of sensitivity to platinum derivatives and PARP enzyme inhibitors. Population studies have indicated a >10% prevalence of BRCA1/2 pathogenic variants with wide variance amongst ethnically different populations. We aim to establish the first population-based cohort to assess the prevalence of BRCA1/2 in ovarian cancer patients throughout Malaysia. Methods : From August 2016, women with non-mucinous epithelial ovarian, peritoneal or fallopian tube cancer are continually being recruited to the MaGiC Observational Study. DNA were tested using a Hi-Plex next generation sequencing method and multiplex ligation‑dependent probe amplification to detect <10bp alterations and exon deletions/duplications in the BRCA1 and BRCA2 genes. Results : Interim results from 208 patients tested until September 2017 have identified BRCA1 and BRCA2 pathogenic variants in 10.1% (21/208) and 2.9% (6/208) patients, respectively. Variants of uncertain significance were detected in 15.9% (33/208) patients and no pathogenic variants were detected in 71.2% (148/208) patients. Taken together, the prevalence of BRCA1/2 in ovarian cancer patients is approximately 13.0% (27/208). Conclusions : To our knowledge, this will be the first population-based cohort of Malaysian women with ovarian, fallopian tube or peritoneal carcinoma. Given the clinical significance of BRCA1/2 pathogenic variants in patient management and cancer risk assessment, the data arising from this study may be beneficial to healthcare professionals in medical practice and genetic service centres in Malaysia. NMRR-16-1322-31114, UMMC 20163-2255 and RSDH 201612.2.