OBJECTIVES: 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. CONCLUSION: 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.
OBJECTIVES: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. MTHFRC677T 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 MTHFR677 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. CONCLUSION: We observed that the MTHFR677 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: M T Goodman; K McDuffie; B Hernandez; L R Wilkens; C C Bertram; J Killeen; L Le Marchand; J Selhub; S Murphy; T A Donlon Journal: Cancer Epidemiol Biomarkers Prev Date: 2001-12 Impact factor: 4.254
Authors: N M van der Put; F Gabreëls; E M Stevens; J A Smeitink; F J Trijbels; T K Eskes; L P van den Heuvel; H J Blom Journal: Am J Hum Genet Date: 1998-05 Impact factor: 11.025
Authors: B C Blount; M M Mack; C M Wehr; J T MacGregor; R A Hiatt; G Wang; S N Wickramasinghe; R B Everson; B N Ames Journal: Proc Natl Acad Sci U S A Date: 1997-04-01 Impact factor: 11.205
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Authors: Sungshim L Park; Delara Bastani; Binh Y Goldstein; Shen-Chih Chang; Wendy Cozen; Lin Cai; Carlos Cordon-Cardo; Baoguo Ding; Sander Greenland; Na He; Shehnaz K Hussain; Qingwu Jiang; Yuan-Chin A Lee; Simin Liu; Ming-Lan Lu; Thomas M Mack; Jenny T Mao; Hal Morgenstern; Li-Na Mu; Sam S Oh; Allan Pantuck; Jeanette C Papp; Jianyu Rao; Victor E Reuter; Donald P Tashkin; Hua Wang; Nai-Chieh Y You; Shun-Zhang Yu; Jin-Kou Zhao; Zuo-Feng Zhang Journal: Carcinogenesis Date: 2010-05-17 Impact factor: 4.944
Authors: Joan Oliva; Fawzia Bardag-Gorce; Jun Li; Barbara A French; Sheila K Nguyen; Shelly C Lu; Samuel W French Journal: Exp Mol Pathol Date: 2008-11-24 Impact factor: 3.362