Incidence of germline BRCA1 and BRCA2 mutations among Filipinos

Abstract

Background: The Philippines has the highest reported incidence of breast cancer (BC) in Southeast Asia, with a rate of 47.7 per 100,000 per year. 5 to 10% of BC results from a hereditary predisposition with majority caused by BRCA1/2 mutations, conferring a lifetime risk of 55-85% and 35-60%, respectively. Little is known about the contribution of BRCA mutations to cancer incidence in the Filipino population. Methods: Patients from St. Luke's Medical Center-Quezon City were enrolled with written informed consent. DNA samples were obtained from a total of 192 subjects (181 females, 11 males; 18-76 years old) who met the National Comprehensive Cancer Network (NCCN) criteria for BRCA genetic testing: 95 had breast cancer (BC), 18 had ovarian cancer, 1 had fallopian tube carcinoma, 4 had concomitant ovarian and BC; 78 had no known cancer diagnosis but with strong family history. Next generation sequencing (NGS) approach for diagnostic mutation screening of the BRCA1/2 gene using the Miseq Illumina platform was performed, followed by confirmation of identified variants by Sanger sequencing. Results: Among 192 patients, 13 (6.77%) were pathogenic, 6 with BRCA1 mutations (2 cases of c.5398delC, 2 cases of c.4148C>G, c.5314C>T, c.2213-2214dupTT) and 7 with BRCA2 mutations (c.3362C>G, 3 cases of c.2176delG, c.8009C>T, 2 cases of c.5851-5854depAGTT). Eight out of 13 patients with pathological variants had breast carcinoma, 1 had DCIS, 1 had ovarian carcinoma, 1 had fallopian tube carcinoma, and 2 were healthy individuals. 10 (5.21%) variants of uncertain significance were identified, which would require further cosegregation analysis. 169 (88.02%) were benign/no pathogenic variant detected. Conclusions: This is the first local study to apply NGS of BRCA1/2 mutation analysis in a Filipino population. This study prompts further investigation of unique variants to enable better understanding of the genetic predisposition to cancer among Filipinos. Benefits of BRCA1/2 mutation testing include optimal treatment tailored for BRCA-positive patients and, more importantly, extending testing to family members and helping them take measures for early detection of cancer.