BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high‐risk pancreatic cancer screening and pancreatic cancer cohorts

Abstract

Background Ten percent of pancreatic ductal adenocarcinoma (PDAC) is due to genetic predisposition, including the breast and ovarian cancer syndrome germline mutations BRCA1 and BRCA2. Knowledge of specific genetic mutations predisposing to PDAC may enable risk stratification, early detection and development of effective screening and surveillance programs. We aimed to determine the diagnostic yield of testing for BRCA1/2 germline mutations in a PDAC screening cohort and a PDAC cohort referred for genetic testing. Methods Patients in a high-risk PDAC prevention and genetics program or with a personal history of PDAC referred for genetic evaluation underwent testing for BRCA1/2 germline mutations. Clinical BRCA1/2 genetic testing included testing for the 3 Ashkenazi Jewish founder mutations or BRCA1/2 comprehensive testing. Results 37 patients without PDAC underwent BRCA1/2 testing at our institution. Genetic testing identified 7 patients who were BRCA1/2 carriers for a yield of 18.9%. Six carried Ashkenazi Jewish founder mutations (3 BRCA1, 3 BRCA2), and 1 had a BRCA2 mutation on comprehensive testing. 32 patients with PDAC underwent BRCA1/2 genetic testing. Five had Ashkenazi Jewish founder mutations (two BRCA1, three BRCA2), and 2 had BRCA2 mutations on comprehensive testing. The diagnostic yield was 7/32 (21.8%). Conclusions BRCA1/2 testing is useful in PDAC risk stratification and alters risk assignment and screening recommendations for mutation positive patients and their families. Clinical BRCA1/2 testing should be considered in patients of Ashkenazi Jewish descent, with a personal history or family history of PDAC, even in the absence of a family history of breast and ovarian cancer.

Global Trends in Pancreatic Cancer Mortality From 1980 Through 2013 and Predictions for 2017

“…36, 37 Those factors, however, contribute less to pancreatic cancer on a population level, 38 and are unlikely to have major impact on worldwide mortality trends.…”

Is it time to split strategies to treat homologous recombinant deficiency in pancreas cancer?

“…The cohort was significantly enriched with germline BRCA2 mutation in 17.2% of the patients while no germline mutations in the other three genes were observed (MP2K4, MADH4 and ACVR1B) (44). A similar study by Lucas and colleagues identified germline BRCA1/2 mutations in 21.9% of 32 patients with pancreatic cancer and 18.9% in patients without a cancer diagnosis currently enrolled in their high-risk pancreatic cancer prevention and genetics program (45). However, the majority of these early studies were significantly restricted by small sample size.…”

BRCA1 and BRCA2 Mutation in Pancreatic Cancer: Significance in Therapeutic Approach

“…It was found that BRCA2 mutation poses an increased risk for developing pancreatic cancer [20]. Some study proposed BRCA2 as a genetic factor as causes of the pancreatic cancer [21]. As like breast cancer, 5-10% of pancreatic cancer cases are believed to be hereditary.…”