Association of genetic variants in autophagy-lysosome pathway genes with susceptibility and survival to prostate cancer.

Abstract

Previous studies have indicated the connections between autophagy-lysosome pathway genes dysfunction and prostate cancer, but few studies have investigated whether single nucleotide polymorphisms (SNPs) in autophagy-lysosome pathway genes are implicated in prostate cancer risk and survival. Logistic regression analysis and stepwise Cox regression analysis were conducted in 4,662 cases and 3,114 controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The false positive rate probability (FPRP) method was applied to correct for multiple comparisons. Gene-based analysis was calculated by versatile gene-based association study approach. We found that SLC11A1 rs7573065 significantly increased the risk of prostate cancer [adjusted odds ratio (OR)=1.24, 95% confidence interval (CI)=1.06-1.46, P=7.02×10-3, FPRP=0.082]. Furthermore, rs7573065 was confirmed as the independent predicator of overall survival (OS) for prostate cancer patients [Hazard ratio (HR)=1.30, 95% CI=1.01-1.66, P=0.041]. The significant association between SLC11A1 and prostate cancer risk was calculated by gene-based analysis (P=0.030). We also observed that the mRNA of SLC11A1 in prostate tumor tissues was significantly over-expressed than that in normal tissues. This study suggested that rs7573065 in SLC11A1 was associated with an increased risk and poor OS of prostate cancer. Our findings may provide evidence for genetic variants in autophagy-lysosome pathway as the risk and prognostic biomarkers for prostate cancer.