Prevalence and Risk Factors of Germline Pathogenic Variants in Pancreatic Ductal Adenocarcinoma

Abstract

Purpose The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC.Materials and Methods Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed.Results PVs were detected in 20 patients (6.7%, median age 65) in <i>ATM</i> (n=7, 31.8%), <i>BRCA1</i> (n=3, 13.6%), <i>BRCA2</i> (n=3), and <i>RAD51D</i> (n=3). Each one patient showed <i>TP53, PALB2, PMS2, RAD50, MSH3,</i> and <i>SPINK1</i> PV. Among them, two likely PVs were in <i>ATM</i> and <i>RAD51D</i>, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with <i>ATM</i> PVs and a patient with three germline PVs (<i>BRCA2, MSH3,</i> and <i>RAD51D</i>) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035).Conclusion Our study demonstrated that germline PVs in <i>ATM, BRCA1, BRCA2,</i> and <i>RAD51D</i> are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.