BACKGROUND: A single nucleotide polymorphism (SNP) C677T in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified. The TT or CT genotypes show a marked reduction of the enzyme activity; this causes higher homocysteine levels and alterations of folate metabolism. Folate metabolism is essential for DNA synthesis and methylation, crucial steps in carcinogenesis. In this paper, we investigated whether the MTHFR C677T SNP could influence the occurrence of hepatocellular carcinoma (HCC) in a cohort of patients transplanted for end stage liver disease of different etiologies. METHODS: Two hundred and twelve consecutive patients who underwent liver transplantation for end stage liver disease due to hepatitis B or C, alcoholic liver disease, and other causes were studied. Two hundred and thirty-six blood donors served as controls. Focal hepatic lesions were searched in the sectioned explanted livers. The presence of the MTHFR C677T SNP was determined via polymerase chain reaction amplification. RESULTS: Among the 65 patients with HCC, 22 had the CC genotype, 30 the CT, and 13 the TT genotype. Only in patients with alcoholic liver disease was a significant association detected between the TT genotype and the presence of liver cancer (6/17 vs. 5/46, p < 0.05). At stepwise logistic regression analysis the independent selected predictors of HCC were found: age at transplantation >55 years (p < 0.001) and the association among male gender, alcoholic liver disease, and MTHFR TT genotype (p = 0.002). CONCLUSIONS: The present study suggests that male TT carriers with alcoholic cirrhosis bear an increased risk of developing HCC.
BACKGROUND: A single nucleotide polymorphism (SNP) C677T in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified. The TT or CT genotypes show a marked reduction of the enzyme activity; this causes higher homocysteine levels and alterations of folate metabolism. Folate metabolism is essential for DNA synthesis and methylation, crucial steps in carcinogenesis. In this paper, we investigated whether the MTHFRC677T SNP could influence the occurrence of hepatocellular carcinoma (HCC) in a cohort of patients transplanted for end stage liver disease of different etiologies. METHODS: Two hundred and twelve consecutive patients who underwent liver transplantation for end stage liver disease due to hepatitis B or C, alcoholic liver disease, and other causes were studied. Two hundred and thirty-six blood donors served as controls. Focal hepatic lesions were searched in the sectioned explanted livers. The presence of the MTHFRC677T SNP was determined via polymerase chain reaction amplification. RESULTS: Among the 65 patients with HCC, 22 had the CC genotype, 30 the CT, and 13 the TT genotype. Only in patients with alcoholic liver disease was a significant association detected between the TT genotype and the presence of liver cancer (6/17 vs. 5/46, p < 0.05). At stepwise logistic regression analysis the independent selected predictors of HCC were found: age at transplantation >55 years (p < 0.001) and the association among male gender, alcoholic liver disease, and MTHFR TT genotype (p = 0.002). CONCLUSIONS: The present study suggests that male TT carriers with alcoholic cirrhosis bear an increased risk of developing HCC.
Authors: Robert Levy; Andreea M Catana; Blythe Durbin-Johnson; Charles H Halsted; Valentina Medici Journal: Alcohol Clin Exp Res Date: 2015-02-20 Impact factor: 3.455
Authors: E Christina Persson; Lauren M Schwartz; Yikyung Park; Britton Trabert; Albert R Hollenbeck; Barry I Graubard; Neal D Freedman; Katherine A McGlynn Journal: Cancer Epidemiol Biomarkers Prev Date: 2013-01-10 Impact factor: 4.254