One-carbon metabolism pathway gene variants and risk of clear cell renal cell carcinoma in a Chinese population

• Published in: PloS one Vol. 8; no. 11; p. e81129
• Main Authors: Zhang, Lei, Meng, Xiaoxin, Ju, Xiaobing, Cai, Hongzhou, Li, Pu, Cao, Qiang, Shao, Pengfei, Qin, Chao, Yin, Changjun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.11.2013; Public Library of Science (PLoS)
• Subjects: Age; Aged; Alleles; Asian Continental Ancestry Group; Cancer; Cancer genetics; Carbon; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - pathology; Case-Control Studies; China; Clear cell-type renal cell carcinoma; Colorectal cancer; Confidence intervals; Deoxyribonucleic acid; Development and progression; Diabetes; Disease susceptibility; DNA; DNA methylation; Female; Gene expression; Genes; Genetic polymorphisms; Genetic Predisposition to Disease; Genotype; Health aspects; Health risks; Hospitals; Humans; Kidney cancer; Kidney Neoplasms - genetics; Male; Medical schools; Metabolism; Methylation; Methylenetetrahydrofolate reductase; Middle Aged; Neoplasm Grading; Neoplasm Staging; Odds Ratio; Patients; Physiological aspects; Polymorphism, Genetic; Population; Population studies; Renal cell carcinoma; Risk; Risk factors; Single-nucleotide polymorphism; Smoking; Studies; Urology; Vitamin B; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0081129

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. 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. 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. 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.