Exome-wide analysis identifies three low-frequency missense variants associated with pancreatic cancer risk in Chinese populations.
case_control · Level III
Where this comes from
- Record sourced from PubMed, PMID 30206226.
- Also identified by DOI 10.1038/s41467-018-06136-x and PMC identifier 6134090.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-10</sup>), rs2242241 in DOK2 (OR = 1.85, 95% CI: 1.50-2.27, P = 4.34 × 10<sup>-9</sup>), and rs183117027 in APOB (OR = 2.34, 95% CI: 1.72-3.16, P = 4.21 × 10<sup>-8</sup>). Functional analyses show that the PKN1 rs34309238 variant significantly increases the level of phosphorylated PKN1 and thus enhances PDAC cells' proliferation by phosphorylating and activating the FAK/PI3K/AKT pathway. These findings highlight the significance of coding variants in the development of PDAC and provide more insights into the prevention of this disease.
Medical subject headings
- Asian People
- Exome
- Genetic Predisposition to Disease
- Mutation Rate
- Mutation, Missense
- Pancreatic Neoplasms