Germline BRCA mutations in Asian patients with pancreatic adenocarcinoma: a prospective study evaluating risk category for genetic testing

• Published in: Investigational new drugs 2018-02, Vol.36 (1), p.163-169
• Main Authors: Lee, Kyoungmin, Yoo, Changhoon, Kim, Kyu-pyo, Park, Kyoung-Jin, Chang, Heung-Moon, Kim, Tae Won, Lee, Jae-Lyun, Lee, Woochang, Lee, Sang Soo, Park, Do Hyun, Song, Tae Jun, Seo, Dong Wan, Lee, Sung Koo, Kim, Myung-Hwan, Shin, Sang Hyun, Hwang, Dae Wook, Song, Ki Byung, Lee, Jae Hoon, Kim, Song Cheol, Ryoo, Baek-Yeol
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asian Continental Ancestry Group - genetics; BRCA1 protein; BRCA1 Protein - genetics; BRCA2 protein; BRCA2 Protein - genetics; Breast; Breast cancer; Breast Neoplasms - genetics; Chemotherapy; Criteria; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; Exons; Female; Gene sequencing; Genetic screening; Genetic Testing; Genetics; Germ-Line Mutation; Health risk assessment; Health risks; Humans; Male; Mammography; Medical History Taking; Medicine; Medicine & Public Health; Metastases; Middle Aged; Minority & ethnic groups; Mutation; Oncology; Ovarian cancer; Ovarian Neoplasms - genetics; Pancreas; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - genetics; Patients; Pharmacology/Toxicology; Progression-Free Survival; Risk; Risk Factors; Short Report; Studies
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-017-0497-1

Summary Introduction Germline BRCA mutations may have therapeutic implications as surrogate markers of DNA-damage repair status in pancreatic ductal adenocarcinoma (PDAC). We performed a prospective study to evaluate the efficiency of risk criteria based on personal or family history of breast and ovarian cancer for determining germline BRCA mutations in PDAC patients with Asian ethnicity. Methods Between November 2015 and May 2016, we screened consecutive PDAC patients with locally advanced unresectable or metastatic disease who were referred for systemic chemotherapy. Analyses for germline BRCA mutations were performed if patients had one or more first-degree or second-degree relatives with breast or ovarian cancers or had a personal medical history of these diseases. DNA was extracted from whole blood, and all coding exons and their flanking intron regions of BRCA1 and BRCA2 were sequenced. Results A total of 175 patients were screened for personal and family history and 10 (5.7%) met the inclusion criteria for genetic sequencing. Pathogenic germline BRCA2 mutation [c.7480C>T (p.Arg2494*)] was identified in one male patient, resulting in a frequency of 10% for the risk-stratified patients and 0.6% for the unselected PDAC population. Two patients had germline BRCA2 variants of uncertain significance [c.1744A>C (p.Thr582Pro) and c.68-7T>A]. Conclusion Personal or family history of breast or ovarian cancers is a feasible, cost-effective risk categorization for screening germline BRCA mutations in Asian PDAC patients as 10% of this population had the pathogenic mutation herein. Future validation from a large, prospective cohort is needed.