Genetic variants in the cholesterol biosynthesis pathway genes and risk of prostate cancer

Previous studies have found the relationship between cholesterol biosynthesis pathway genes and the risk or prognosis of prostate cancer (PCa), while there is no definite evidence that genetic variants in the cholesterol biosynthesis pathway gene is related to PCa risk. Consequently, we performed this study to explore the associations of single-nucleotide polymorphisms (SNPs) in the cholesterol biosynthesis pathway with PCa risk. We systematically evaluated the association of SNPs in 21 cholesterol biosynthesis pathway genes with the risk of PCa using the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial database using a logistic regression model. Gene expression data of PCa from Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA) database were applied for mRNA expression analysis. The TCGA database was used to perform expression quantitative trait loci (eQTL) analysis. The interaction between demographic factors and SNPs was analyzed using two-by-four tables. We found T allele of rs67415672 in HMGCS1 is a significant protective allele of PCa [adjusted odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.83-0.97, P = 4.16 × 10^-3]. Moreover, rs67415672 was an eQTL for HMGCS1 (P = 2.23 × 10^-6). The expression of HMGCS1 significantly decreased in PCa primary tumors than that in normal tissues. These findings indicated that the HMGCS1 rs67415672 might be possible functional susceptibility loci for PCa.