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.

先前的研究已经发现胆固醇生物合成途径基因与前列腺癌（PCa）的风险或预后之间的关系，而没有确凿证据表明胆固醇生物合成途径基因的遗传变异与PCa风险有关。因此，我们进行了这项研究，以探讨胆固醇生物合成途径中的单核苷酸多态性（SNP）与PCa风险的关联。我们使用前列腺癌，肺癌，结肠直肠癌和卵巢癌（PLCO）癌症筛查试验数据库，通过逻辑回归模型，系统地评估了21种胆固醇生物合成途径基因中SNP与PCa风险的相关性。将来自基因表达综合（GEO）数据集和癌基因组图谱（TCGA）数据库的PCa的基因表达数据用于mRNA表达分析。TCGA数据库用于执行表达定量性状基因座（eQTL）分析。使用二乘四表分析了人口统计学因素与SNP之间的相互作用。我们在以下位置找到了rs67415672的T等位基因HMGCS1是PCa的重要保护等位基因[调整比值比（OR）= 0.90，95％置信区间（CI）= 0.83-0.97，P = 4.16×10 ^-3 ]。此外，rs67415672是用于eQTL HMGCS1（P = 2.23×10 ^-6）。PCa原发性肿瘤中HMGCS1的表达明显低于正常组织。这些发现表明，HMGCS1 rs67415672可能是PCa的功能敏感性基因座。