Dongliang Cao1, Yixuan Meng2, Shuwei Li2, Junyi Xin2, Shuai Ben2, Yifei Cheng1, Meilin Wang2, Lixin Hua1, Gong Cheng1. 1. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China. 2. Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Abstract
BACKGROUND: Evidence suggests that serum retinol level is associated with prostate cancer risk, but the association between genetic variants in the retinol metabolism pathway genes and prostate cancer risk remains unclarified. METHODS: Single-nucleotide polymorphisms (SNPs) in 31 genes in the retinol metabolism pathway were genotyped to evaluate the association with prostate cancer risk in 4,662 cases and 3,114 controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The gene expression analysis was evaluated using data from the Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA) database. Data from the Genotype-Tissue Expression (GTEx) project dataset were utilized to perform the expression quantitative trait loci (eQTL) analysis. RESULTS: Two SNPs were significantly associated with prostate cancer risk [rs1330286 in ALDH1A1: odds ratio (OR) = 0.88, 95% confidence interval (CI) = 0.83-0.94, p = 2.45 × 10-4 ; rs4646653 in ALDH1A3: OR = 1.17, 95% CI =1.07-1.27, p = 4.33 × 10-4 ]. Moreover, the mRNA level of ALDH1A3 was significantly higher in prostate cancer tissues than in normal tissues in both TCGA datasets and GEO datasets (p = 1.63 × 10-12 and p = 4.33 × 10-2 , respectively). rs1330286 was an eQTL of ALDH1A1 (P = 2.90 × 10-3 ). CONCLUSION: Our findings highlight that genetic variants in retinol metabolism pathway genes are associated with prostate cancer risk.
BACKGROUND: Evidence suggests that serum retinol level is associated with prostate cancer risk, but the association between genetic variants in the retinol metabolism pathway genes and prostate cancer risk remains unclarified. METHODS: Single-nucleotide polymorphisms (SNPs) in 31 genes in the retinol metabolism pathway were genotyped to evaluate the association with prostate cancer risk in 4,662 cases and 3,114 controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The gene expression analysis was evaluated using data from the Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA) database. Data from the Genotype-Tissue Expression (GTEx) project dataset were utilized to perform the expression quantitative trait loci (eQTL) analysis. RESULTS: Two SNPs were significantly associated with prostate cancer risk [rs1330286 in ALDH1A1: odds ratio (OR) = 0.88, 95% confidence interval (CI) = 0.83-0.94, p = 2.45 × 10-4 ; rs4646653 in ALDH1A3: OR = 1.17, 95% CI =1.07-1.27, p = 4.33 × 10-4 ]. Moreover, the mRNA level of ALDH1A3 was significantly higher in prostate cancer tissues than in normal tissues in both TCGA datasets and GEO datasets (p = 1.63 × 10-12 and p = 4.33 × 10-2 , respectively). rs1330286 was an eQTL of ALDH1A1 (P = 2.90 × 10-3 ). CONCLUSION: Our findings highlight that genetic variants in retinol metabolism pathway genes are associated with prostate cancer risk.
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