Abstract
Clinicopathologic and genetic features of familial pancreatic cancer (FPC) in Asian countries remain largely unknown. The main purpose of this study was to determine the prevalence of FPC and to define causative FPC-predisposition genes in a Japanese cohort with pancreatic ductal adenocarcinoma (PDAC). We reviewed 1,197 patients with a pathologically proven PDAC and found that 88 (7.3%) were FPC patients who had at least one first-degree relative with PDAC. There were no significant differences between the FPC cases and sporadic cases in terms of gender, age, tumor location, stage, family history of any cancer except PDAC, and personal history of smoking, other cancers, diabetes mellitus and chronic pancreatitis. In the FPC patients, we then investigated the prevalence of germline mutations in 21 genes associated with hereditary predispositions for pancreatic, breast and ovarian cancers by means of the next-generation sequencing using a custom multiple-gene panel. We found that eight (14.5%) of the 54 FPC patients with available germline DNA carried deleterious mutations in BRCA2, PALB2, ATM, or MLH1. These results indicate that a significant fraction of patients with PDAC in Japan have a family history of pancreatic cancer, and some of them harbor deleterious causative mutations in known FPC predisposition genes.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is a devastating diagnosis for patients and their families [1]
The main purpose of this study was to determine the prevalence of familial pancreatic cancer (FPC) and to define causative FPC-predisposition genes in a Japanese cohort with pancreatic ductal adenocarcinoma (PDAC).We reviewed 1,197 patients with a pathologically proven PDAC and found that 88 (7.3%) were FPC patients who had at least one first-degree relative with PDAC
These results indicate that a significant fraction of patients with PDAC in Japan have a family history of pancreatic cancer, and some of them harbor deleterious causative mutations in known FPC predisposition genes
Summary
Pancreatic ductal adenocarcinoma (PDAC) is a devastating diagnosis for patients and their families [1]. In Japan, the incidence and mortality have shown an increasing trend over the past decades [2] and incidence and mortality rates are approximately twice of those in the United States [3]. A generally accepted definition of familial pancreatic cancer (FPC) is presence of at least a pair of affected first-degree relatives (FDRs: sibling–sibling or parent-child) in the family [5]. Of patients with PDAC is familial in the United States [6] and individuals with a family history of PDAC have been shown to have a greatly elevated risk of developing PDAC themselves [5]. The prevalence of deleterious mutations in these genes varies significantly in different populations (e.g., Ashkenazi Jews have high rates of germline BRCA2 mutations) [10]
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