Genetic variants and risk of prostate cancer using pathway analysis of a genome-wide association study.

Abstract

This study explored candidate causal single nucleotide polymorphisms (SNPs) to clarify the biological mechanism of prostate cancer (PCa). Identify candidate Causal SNPs and Pathways (ICSNPathway) analysis was applied using a PCa genome-wide association study (GWAS) dataset that included 473,736 SNPs in 1151 cases of PCa and 1156 controls of European ancestry. Five candidate causal SNPs, three candidate causal genes, and two candidate causal pathways were identified using integrating linkage disequilibrium analysis, functional SNP annotation, and pathway-based analysis. The ICSNPathway analysis suggested three hypothetical mechanisms of PCa. The first was rs13112390, rs13112358, rs2048074 to nei-like DNA glycosylase 3 (NEIL3) gene to damaged DNA binding. The second was rs3087386 to REV1, DNA directed polymerase (REV1) gene to damaged DNA binding. The third was rs1063134 to potassium channel, inwardly rectifying subfamily J, member 4 (KCNJ4) gene to inward rectifier potassium channel activity.