Frequency of BRCA1 and BRCA2 Germline Variants in Women With Ovarian Cancer in Malaysia
Lim J., Lau SY., Bashah NSA., Lai KN., Wen WX., Hasan SN., Park DJ., Pope BJ., Nguyen-Dumont T., Southey MC., Rahman N., Woo YL., Thong MK., Ch'ng GS., Teo SH., Yoon SY.
<jats:p> Background: Germline BRCA1 or BRCA2 pathogenic variants in ovarian cancer patients may be informative in risk management and treatment, with the advent of poly(ADP-ribose) polymerase inhibitors. In the era of precision medicine, companion diagnostics for BRCA1 and BRCA2 genes have been featured as a strategy in the Malaysia National Strategic Plan for Cancer Control Program (2016-2020). To facilitate this strategy, frequency data from Malaysia's understudied multiethnic population will be required. Aim: To determine the prevalence of BRCA1 and BRCA2 germline variants in a population-based cohort of ovarian cancer patients in Malaysia. Methods: From August 2016, women with nonmucinous epithelial ovarian, peritoneal or fallopian tube carcinoma are prospectively recruited to the Malaysia-wide population-based MaGiC Observational Study. DNA were tested using a Hi-Plex next generation sequencing method and multiplex ligation-dependent probe amplification to detect < 10 bp alterations and exon deletions or duplications in the BRCA1 and BRCA2 genes. Results: Interim results from 325 patients tested until March 2018 have identified BRCA1 and BRCA2 pathogenic variants in 9.8% (32/325) and 3.1% (10/325) patients, respectively. Variants of uncertain significance were detected in 13.2% (43/325) patients and no pathogenic variants were detected in 73.8% (240/325) patients. Taken together, the frequency of BRCA1/2 pathogenic variants in ovarian cancer patients is approximately 12.9% (42/325). Conclusion: The identification of BRCA1 or BRCA2 carriers across the country have enabled the concentration of efforts from limited genetic counseling resources to high risk families. Results arising from the completion of this study will supplement cancer control programs and genetic services in Malaysia. </jats:p>