title: One-carbon metabolism pathway gene variants and risk of clear cell renal cell carcinoma in a Chinese population.
abstract: 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.
authors.affiliation: Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Meng
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Ju
authors.forename: Hongzhou
authors.initials: H
authors.lastname: Cai
authors.forename: Pu
authors.initials: P
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cao
authors.forename: Pengfei
authors.initials: P
authors.lastname: Shao
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D011110:Polymorphism, Genetic