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Relationships between folate status, genetic polymorphisms in the methylenetetrahydrofolate reductase and thymidylate synthase genes and susceptibility to hepatocellular carcinoma
Author(s) -
Kuo Chang Sheng,
Huang RweiFen Syu
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.728.4
Subject(s) - methylenetetrahydrofolate reductase , genotype , thymidylate synthase , allele , medicine , biology , homocysteine , hepatocellular carcinoma , gastroenterology , methyltransferase , genetics , endocrinology , gene , methylation , cancer , fluorouracil
The aims of the study were to investigate interactive relationships between serum folate levels, MTHFR and TS genetic polymorphisms and risks of HCC development. Genotypes of MTHFR C677T, a 28‐bp tandem repeat in the TS 5′‐untranslated enhanced region, and a 6‐bp deletion/insertion in the 3′‐untranslated region were determined on 190 HCC cases and 190 healthy control subjects. Serum samples were assayed for folate and homocysteine (Hcy) concentrations. The data revealed that serum folate of HCC patients was lower and Hcy concentrations were higher than those of controls (P < 0.05). The distributions of CT/TT genotypes significantly differ between HCC patients and controls (P = 0.018). Subjects with the CT/TT genotype had a decreased risk for HCC relative to those with CC genotype, particularly among individuals with adequate folate status (serum folate > 14 nmol/L). Relative to those with low folate status, individuals with adequate folate status had a significant 80–90% reduction in risk of HCC. The MTHFR CT/TT genotype in conjunction with TSER or TS 3′UTR polymorphisms was associated with a statistically nonsignificant 50–60% reduction in risk of HCC as compared with the CC genotype. Taken together, our data supports the hypothesis that adequate folate status in combination with at least one mutant allele in MTFHR C677T or/and TSER or TS 3′UTR genotype may protect against the development of HCC.