Exome-wide analysis identifies three low-frequency missense variants associated with pancreatic cancer risk in Chinese populations.

ABSTRACT: Germline coding variants have not been systematically investigated for pancreatic ductal adenocarcinoma (PDAC). Here we report an exome-wide investigation using the Illumina Human Exome Beadchip with 943 PDAC cases and 3908 controls in the Chinese population, followed by two independent replicate samples including 2142 cases and 4697 controls. We identify three low-frequency missense variants associated with the PDAC risk: rs34309238 in PKN1 (OR = 1.77, 95% CI: 1.48-2.12, P = 5.35 × 10^-10), rs2242241 in DOK2 (OR = 1.85, 95% CI: 1.50-2.27, P = 4.34 × 10^-9), and rs183117027 in APOB (OR = 2.34, 95% CI: 1.72-3.16, P = 4.21 × 10^-8). Functional analyses show that the PKN1 rs34309238 variant significantly increases the level of phosphorylated PKN1 and thus enhance

SUBMITTER: Chang J 

PROVIDER: S-EPMC6134090 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature