Risk factors and genetic predisposition

Pancreatic cancer (PC) is the third leading cause of cancer-related mortality in the USA and the seventh worldwide. More than 90% of PCs are exocrine pancreatic ductal adenocarcinomas. Major modifiable risk factors of PC include cigarette smoking, obesity, and type 2 diabetes. Other risk factors include heavy alcohol consumption, chronic pancreatitis, and family history. The majority (>90%) of PC cases are sporadic (not inherited), while those with familial PCs have at least two first-degree family members with this cancer and account for about 7% of cases. Genetic susceptibility to sporadic PC has been investigated in genome-wide association studies and high-throughput-sequencing based studies. Numerous susceptibility loci or gene variants (e.g. ABO, NR5A2, PDX1, and TRET) have been identified. In familial PC cases, germline mutations (e.g. PRSS1, CFTR, STK11, BRCA1/2, CDKN2A, MLH1, MSH2, PALB2, FANCC, and ATM) associated with cancer syndromes or other inherited diseases have been identified.