One-Carbon Metabolism Pathway Gene Variants and Risk of Clear Cell Renal Cell Carcinoma in a Chinese Population

Background: One-carbon metabolism is the basement of nucleotide synthesis and the methylation of DNA linked to cancer risk. Variations in one-carbon metabolism genes are reported to affect the risk of many cancers, including renal cancer, but little knowledge about this mechanism is known in Chinese population. Methods: Each subject donated 5 mL venous blood after signing the agreement. The study was approved by the Institutional Review Board of the Nanjing Medical University, Nanjing, China. 18 SNPs in six one-carbon metabolism-related genes (CBS, MTHFR, MTR, MTRR, SHMT1, and TYMS) were genotyped in 859 clear cell renal cell carcinoma (ccRCC) patients and 1005 cancer-free controls by the Snapshot. Results: Strong associations with ccRCC risk were observed for rs706209 (P = 0.006) in CBS and rs9332 (P = 0.027) in MTRR. Compared with those carrying none variant allele, individuals carrying one or more variant alleles in these two genes had a statistically significantly decreased risk of ccRCC [P = 0.001, adjusted odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.06-0.90]. In addition, patients carrying one or more variant alleles were more likely to develop localized stage disease (P = 0.002, adjusted OR = 1.37, 95% CI = 1.11-1.69) and well-differentiated ccRCC (P, 0.001, adjusted OR = 1.42, 95% CI = 0.87-1.68). In the subgroup analysis, individuals carrying none variant allele in older group (P = 0.007, adjusted OR = 0.67, 95% CI = 0.49-0.91), male group (P = 0.007, adjusted OR = 0.71, 95% CI = 0.55-0.92), never smoking group (P = 0.002, adjusted OR = 0.68, 95% CI = 0.53-0.88) and never drinking group (P, 0.001, adjusted OR = 0.68, 95% CI = 0.53-0.88) had an increased ccRCC risk. Conclusions: Our results suggest that the polymorphisms of the one-carbon metabolism-related genes are associated with ccRCC risk in Chinese population. Future population-based prospective studies are required to confirm the results.