title: Genetic variations in the one-carbon metabolism pathway genes and susceptibility to hepatocellular carcinoma risk: a case-control study.
abstract: Hepatocellular carcinoma (HCC) is the sixth common cancer and the third common cause of cancer mortality worldwide. However, the exact molecular mechanism of HCC remains uncertain. Many enzymes are involved in one-carbon metabolism (OCM), and single nucleotide polymorphisms (SNPs) in the corresponding genes may play a role in liver carcinogenesis. In this study, we enrolled 1500 HCC patients and 1500 cancer-free controls, which were frequency-matched by age, gender, and HBV infection status. Then eight SNPs from seven OCM genes (MTHFR, MTR, MTRR, FTHFD, GART, SHMT, and CBS) were evaluated. Results showed that six SNPs (MTHFR rs1801133, MTRR rs2287780, MTRR rs10380, FTHFD rs1127717, GART rs8971, and SHMT rs1979277) were significantly associated with HCC risk in Chinese population, with P values range from 2.26 × 10(-4) to 0.035). The most significant association was detected for GART rs8971. Compared with individuals with the TT genotype, the age- and sex-adjusted odds ratio (OR) for developing HCC was 1.44 (95% confidence interval (CI): 1.03-2.02) among those with the CC genotype and 1.30 (95% CI: 1.10-1.53) for those with CT genotype. Under the log-additive model, each additional copy of minor allele C was associated with a 1.28-fold increased risk of HCC (OR = 1.28, 95% CI: 1.12-1.45). These findings indicated that genetic variants in OCM genes might contribute to HCC susceptibility.
authors.affiliation: China Medical University, Shenyang, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.forename: Chunhe
authors.initials: C
authors.lastname: Liu
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Han
authors.forename: Zuohong
authors.initials: Z
authors.lastname: Ma
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhang
authors.forename: Yinan
authors.initials: Y
authors.lastname: Ma
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People; D019731:Carbon-Nitrogen Ligases / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019875:One-Carbon Group Transferases / Q000235:genetics*; D051026:Phosphoribosylglycinamide Formyltransferase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D019875:One-Carbon Group Transferases; D051026:Phosphoribosylglycinamide Formyltransferase; D019731:Carbon-Nitrogen Ligases; C494823:GART protein, human