Abstract
Polymorphisms in one-carbon metabolism genes may influence the susceptibility to hepatocellular carcinoma (HCC). In the present study, we studied methylenetetrahydrofolate reductase (MTHFR) tagging polymorphisms in 584 HCC cases and 923 controls. Polymerase chain reaction was harnessed to detect MTHFR genotype. Overall, our results showed that genotype distribution of MTHFR rs4846048 and rs4845882 polymorphisms was not different between HCC patients and controls. MTHFR rs9651118 and rs1801133 loci were protective factors for HCC (rs9651118: CT vs. TT: adjusted odds ratio (OR) = 0.67, 95% confidence interval (CI): 0.49–0.90, P=0.008 and TC/CC vs. TT: adjusted OR = 0.70, 95% CI: 0.53–0.93, P=0.015; rs1801133: GA vs. GG: adjusted OR = 0.72, 95% CI: 0.54–0.97, P=0.031, AA/GA vs. GG: adjusted OR = 0.76, 95% CI: 0.57–0.99, P=0.045). However, MTHFR rs3753584 locus was a candidate for susceptibility to HCC (CT vs. TT: adjusted OR = 1.67, 95% CI: 1.20–2.32, P=0.003 and TC/CC vs. TT: adjusted OR = 1.59, 95% CI: 1.15–2.20, P=0.005). Results of haplotype analysis suggested that MTHFR Grs1801133Trs3753584Grs4845882Ars4846048Trs9651118 was associated with the risk of HCC (OR = 1.55, 95% CI: 1.16–2.07, P=0.003). The power of our study also confirmed these associations (the value of power >0.80). In summary, our findings suggested that MTHFR rs3753584, rs9651118 and rs1801133 polymorphisms may affect the risk of HCC in Chinese Han population. In future, our findings should be further validated in additional case–control studies.
Highlights
In 2015, liver cancer (LC) ranked the third most frequent type of malignancy in males and the sixth most frequent type in females, approximately 343700 and 122300 cases occuring in China, respectively [1]
We found that Methylenetetrahydrofolate reductase (MTHFR) rs1801133 and rs9651118 polymorphisms were associated with the decreased risk of hepatocellular carcinoma (HCC) in no chronic hepatitis B virus (HBV) infection subgroup
The HCC susceptibility to individuals may be affected by certain environmental risk factors [27,28]
Summary
In 2015, liver cancer (LC) ranked the third most frequent type of malignancy in males and the sixth most frequent type in females, approximately 343700 and 122300 cases occuring in China, respectively [1]. The total LC-related deaths are the third most frequent type of malignancy [1,2]; the etiology of LC remains unclear. Susceptibility factors [e.g. hepatitis B virus (HBV), age, obesity, type 2 diabetes, consumption of food contaminated with aflatoxin, nonalcoholic fatty liver disease, heavy drinking related cirrhosis, and tobacco use] may be implicated in the etiology of LC [3,4,5,6,7]. Folic acid is important for DNA synthesis and methylation, mitosis and controlling related gene expression. Epidemiological investigations showed that sufficient fruits and vegetables intake may be a protective factor for carcinogenesis [8,9,10]. It is thought that these potential protective roles of diet attribute to the high level intake of folic acid. Methylenetetrahydrofolate reductase (MTHFR) plays an important role in catalyzing the transition of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate
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