Genetic variants in choline metabolism pathway are associated with the risk of bladder cancer in the Chinese population.

Choline metabolism alteration is considered as a metabolic hallmark in cancer, reflecting the complex interactions between carcinogenic signaling pathways and cancer metabolism, but little is known about whether genetic variants in the metabolism pathway contribute to the susceptibility of bladder cancer. Herein, a case-control study comprising 580 patients and 1,101 controls was carried out to analyze the association of bladder cancer with genetic variants on candidate genes involved in the choline metabolism pathway using unconditional logistic regression. Gene expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were applied for differential gene expression analysis. Cox regression was also applied to estimate the role of candidate genes on bladder cancer prognosis. Our results demonstrated that C allele of rs6810830 in ENPP6 was a significant protective allele of bladder cancer, compared to the T allele [Odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.64-0.86, P = 7.14 × 10-5 in additive model]. Besides, we also found that the expression of ENPP6 remarkably decreased in bladder tumors compared with normal tissues. Moreover, high expression of ENPP6 was associated with worse overall survival (OS) in bladder cancer patients [hazard ratio (HR) with their 95% CI 1.39 (1.02-1.90), P = 0.039]. In conclusion, our results suggested that SNP rs6810830 (T > C) in ENPP6 might be a potential susceptibility loci for bladder cancer, and these findings provided novel insights into the underlying mechanism of choline metabolism in cancers.