Purpose: We investigated the clinical relevance and spectrum of BRCA1/2 mutations in Korean ovarian cancer (KoOC) patients.
Materials and methods: Two hundred seventy-nine KoOC patients were enrolled from three university hospitals between 2012 and 2017. Their peripheral blood samples were obtained for BRCA1/2 mutation analysis by direct sequencing. Clinicopathological characteristics were retrospectively reviewed, and spectrum analyses of BRCA1/2 mutation were assessed by systematic literature review.
Results: Frequency of BRCA1/2 mutations was 16.5% in KoOC patients. BRCA1/2 mutations were significantly associated with family history of breast/ovarian cancer (p<0.001), serous histology (p=0.044), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV, p=0.018) but not with early age-of-onset (age < 50, p=0.729). Literature review of BRCA1/2 mutations in KoOC patients found 111 (55 distinct) mutations with high proportion of Korean-specific mutations (24/55, 43.6%). Comparing the spectrum of BRCA1/2 mutation between KoOC and Korean breast cancer (KoBC) patients, the ratio of BRCA1-to-BRCA2 mutations was different, with BRCA1 (78.4%) being predominant in KoOC and BRCA2 in KoBC (59.2%). The most common mutation also differed between the two (c.3627insA of BRCA1 in KoOC and c.7480C>T of BRCA2 in KoBC).
Conclusion: The clinical relevance of BRCA1/2 mutations in KoOC patients was confirmed but that of early age-of-onset was not. Possible inconsistency in the ratio of BRCA1-to-BRCA2 mutations and the most common mutation between KoOC and KoBC may probably suggest presence of mutation sequence-associated penetrance tendency in hereditary Korean breast and ovarian cancer. These data may provide insights for optimal genetic counseling and prophylactic treatment for at-risk relatives of KoOC patients.
Keywords: BRCA1 genes; BRCA2 genes; Germ-line mutation; Koreans; Ovarian neoplasms.