title: Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and the risk of primary hepatocellular carcinoma (HCC) in a Chinese population.
abstract: OBJECTIVE
  Methylenetetrahydrofolate reductase (MTHFR), which is expressed in the liver, may be involved in both DNA methylation and DNA synthesis. It is also indicated as a potential risk factor of liver cancer in patients with chronic liver disease. To date, no study has been conducted on MTHFR and hepatocellular carcinoma (HCC) using a population-based design. The objective of this study was to evaluate the effects of polymorphisms of the MTHFR gene on the risk of primary liver cancer and their possible effect modifications on various environmental risk factors.
  
  
  METHODS
  A population-based case-control study was conducted in Taixing, China. MTHFR C677T and A1298C were assayed by PCR-RFLP techniques.
  
  
  RESULTS
  The frequency of MTHFR 677 C/C wild homozygotes genotype was 25.8% in cases, which was lower than that in controls (34.5%). The adjusted odds ratios (ORs) for the MTHFR 677 C/T and T/T genotype were 1.66(95% CI: 1.06-2.61), 1.21(95% CI: 0.65-2.28) respectively when compared with the MTHFR 677 C/C genotype. Subjects carrying any T genotype have the increased risk of 1.55(95% CI: 1.01-2.40) for development of primary hepatocellular carcinoma. A high degree of linkage disequilibrium was observed between the C677T and A1298C polymorphisms, with the D' of 0.887 and p < 0.01. The MTHFR 677 any T genotype was suggested to have potentially more than multiplicative interactions with raw water drinking with p-value for adjusted interaction of 0.03.
  
  
  CONCLUSIONS
  We observed that the MTHFR 677 C/T genotype was associated with an increased risk of primary liver cancer in a Chinese population. The polymorphism of MTHFR 677 might modify the effects of raw water drinking on the risk of primary hepatocellular carcinoma.
authors.affiliation: Department of Epidemiology, Fudan University School of Public Health, Shanghai, China. lina.Mu@yale.edu
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Mu
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Zuo-Feng
authors.initials: ZF
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.forename: Qing-Wu
authors.initials: QW
authors.lastname: Jiang
authors.forename: Nai-Chieh
authors.initials: NC
authors.lastname: You
authors.forename: Binh Yang
authors.initials: BY
authors.lastname: Goldstein
authors.forename: Guo-Rong
authors.initials: GR
authors.lastname: Wei
authors.forename: Chuan-Wei
authors.initials: CW
authors.lastname: Chen
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Lu
authors.forename: Xue-Fu
authors.initials: XF
authors.lastname: Zhou
authors.forename: Bao-Guo
authors.initials: BG
authors.lastname: Ding
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.forename: Shun-Zhang
authors.initials: SZ
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)