Abstract 4279: Germline BRCA mutations in Asian patients with locally advanced unresectable or metastatic pancreatic adenocarcinoma (PDAC): Risk categories for genetic testing in Asian population
Authors: Lee Kyoungmin , Yoo Changhoon , Kim Kyu-pyo , Chang Heung-Moon , Kwak Hyerim , Kim Tae Wom , Lee Jae Lyun , Ryoo Baek-Yeol 
Published: July 2017

Background: Familial PDAC constitutes of 5-10% of all PDAC, and germline mutations in BRCA1 and BRCA2 are associated with increased risk of PDAC. Although previous studies showed the prevalence of BRCA1 and BRCA2 germline mutations in patients with PDAC ranged between 3% and 21%, these data have been mostly based on the Western patient population. Considering ethnic differences in the prevalence of the mutations in these genes, we performed prospective evaluation to analyze the prevalence of BRCA1 and BRCA2 mutations in PDAC patients with Asian ethnicity.

Methods: Between November 2015 and May 2016, all consecutive PDAC patients with locally advanced unresectable or metastatic disease who were referred for systemic chemotherapy in Asan Medical Center, Seoul, Korea were included. Mutation analysis for germline BRCA1 and BRCA2 were performed for patient with one or more first- or second-degree relatives with breast or ovarian cancers, or past medical history of these diseases. Germline DNA was extracted from 10 cc of whole blood and analyzed for 23 coding exons of BRCA1 and 26 coding exons of BRCA2 using Sanger sequencing.

Results: A total of 175 potential participants with locally advanced unresectable or metastatic PDAC were identified during the study period. Among them, 10 (5.7%) patients met the criteria for further analysis of germline BRCA1 and BRCA2 mutations. Six (60%) patients had family history of breast or ovarian cancers and four (40%) patients had previous medical history of breast cancer. The median age was 60 years (range 49-72) and 5 patients (50%) were male. Pathogenic germline BRCA2 mutation (7480C&gt;T) was identified in one male patient (10%) with family history of breast cancer. Two patients had germline BRCA2 mutations (68-7T&gt;A and 1744A&gt;C), which were regarded as the variants of uncertain significance (VUS).

Conclusion: Germline BRCA mutations, potentially clinically meaningful, were identified in 1.7% (3/175) of overall patients with locally advanced or metastatic PDAC and 30% (3/10) of patients with past or family history of breast or ovarian cancers. Our results indicate that the prevalence of BRCA mutation in Asian PDAC population is lower than Western patients. Risk category used in this study (past medical history or one or more first- or second-degree relatives with breast or ovarian cancers) may be the feasible criteria for germline BRCA mutation analysis in PDAC patients with Asian ethnicity.

Citation Format: Kyoungmin Lee, Changhoon Yoo, Kyu-pyo Kim, Heung-Moon Chang, Hyerim Kwak, Tae Wom Kim, Jae Lyun Lee, Baek-Yeol Ryoo. Germline BRCA mutations in Asian patients with locally advanced unresectable or metastatic pancreatic adenocarcinoma (PDAC): Risk categories for genetic testing in Asian population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4279. doi:10.1158/1538-7445.AM2017-4279