title: Genetic Polymorphism of MTHFR C677T Influences Susceptibility to HBV-Related Hepatocellular Carcinoma in a Chinese Population: a Case-Control Study.
abstract: BACKGROUND
  Methylene tetrahydrofolate reductase (MTHFR) is the key enzyme of folic acid metabolism and the C677T mutation is associated with decreased enzyme activity. Several studies have shown its regulatory role in carcinogenesis and tumor growth. HBV (hepatitis B virus)-related HCC (hepatocellular carcinoma) is one of the most common liver cancers worldwide. Therefore, the present case-control study aimed to investigate the role of genetic polymorphism of MTHFR C677T in the development and progression of HBV-related HCC in a Chinese population.
  
  
  METHODS
  Subjects enrolled included 204 HBV-related HCC patients and 211 HBV infected patients without HCC. MTHFR C677T polymorphism was genotyped via a DNA microarray-based assay. The relationship between the MTHFR C677T polymorphism and HBV-related HCC was analyzed.
  
  
  RESULTS
  The genotype frequencies of MTHFR C677T were statistically different between the HCC and control groups (p = 0.025). The TT genotype was associated with elevated risk of HBV-related HCC in a Chinese population under different genetic models after an adjustment for age, gender, HBV infection duration, and HCC family history (T vs. C, OR = 1.462, 95% CI: 1.090 - 1.962, p = 0.011; TT vs. CC, OR = 2.151, 95% CI: 1.143 - 4.049, p = 0.018; TT vs. CC+CT, OR = 1.918, 95% CI: 1.215 - 3.026, p = 0.005). When stratified with the known duration of HBV infection, subjects with HBV infection duration of more than 20 years and carrying the homozygous TT genotype had a higher susceptibility to HCC than those with the C allele (CC/CT) (OR = 2.568, 95% CI: 1.244 - 5.303; p = 0.011). There was no significant association between MTHFR C677T genotypes and HCC stages based on BCLC staging system.
  
  
  CONCLUSIONS
  MTHFR C677T polymorphism with TT genotype could be a factor that increases the risk of HBVrelated HCC in a Chinese population, especially those with HBV infection duration of more than 20 years.
authors.forename: Kunyan
authors.initials: K
authors.lastname: Qiao
authors.forename: Shitian
authors.initials: S
authors.lastname: Zhang
authors.forename: Congdoanh
authors.initials: C
authors.lastname: Trieu
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Dai
authors.forename: Zhixiao
authors.initials: Z
authors.lastname: Huo
authors.forename: Yanan
authors.initials: Y
authors.lastname: Du
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
mesh_terms: D006528:Carcinoma, Hepatocellular; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006509:Hepatitis B; D006801:Humans; D008113:Liver Neoplasms; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)