Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms in patients with small cell and non-small cell lung cancer

Siemianowicz, Krzysztof; Gmiński, Jan; Garczorz, Wojciech; Slabiak, Natalia; Goss, M; Machalski, M; Magiera-Molendowska, H

doi:10.3892/or.10.5.1341

Cited by 32 publications

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“…Some of these studies reported that MTHFR 677T allele carriers have reduced risks of colorectal [5][6][7][8][9], leukemia [10][11][12], and lung cancers [29]. In contrast, other studies reported elevated risks of esophageal [17], gastric [18], ovarian [30], cervical [14], bladder [13], colorectal [31,32], and lung cancers [33] for MTHFR 677T allele carriers. These conflicting results might be explained by the modifying effects of the MTHFR polymorphisms on the balance between DNA methylation and DNA synthesis.…”

Section: Discussionmentioning

confidence: 99%

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and the risk of primary Hepatocellular Carcinoma (HCC) in a Chinese population

Cao

Zhang

et al. 2007

Cancer Causes Control

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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 homo-zygotes 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.

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Section: Discussionmentioning

confidence: 99%

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and the risk of primary Hepatocellular Carcinoma (HCC) in a Chinese population

Cao

Zhang

et al. 2007

Cancer Causes Control

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“…The roles of these polymorphisms in the risk of various cancers, including lung cancer, have been studied (17)(18)(19)(20)(21)(22)(23)(24), but the results have been inconsistent (17,22,23), suggesting phenotypic and genotypic heterogeneity. In addition, these published studies did not include all three nonsynonymous single nucleotide polymorphisms and all have had relatively small sample sizes without the statistical power to identify a susceptible subgroup or to detect gene-environment interactions.…”

Section: Introductionmentioning

confidence: 99%

Sex Differences in Risk of Lung Cancer Associated with Methylene-tetrahydrofolate Reductase Polymorphisms

Shi

Zhang

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotides needed for DNA synthesis and repair. Variations in MTHFR functions likely play roles in the etiology of lung cancer. The MTHFR gene has three nonsynonymous single nucleotide polymorphisms (i.e., C677T, A1298C, and G1793A) that have a minor allele frequency of >5%. We investigated the associations between the frequencies of MTHFR variant genotypes and risk of lung cancer in a hospital-based case-control study of 1,051 lung cancer patients and 1,141 cancer-free controls in a nonHispanic White population. We found that compared with the MTHFR 1298AA genotype, the 1298CC genotype was associated with a significantly increased risk of lung cancer in women [(odds ratio (OR), 2.09; 95% confidence interval (95% CI), 1.32-3.29)] but not in men (OR, 0.95; 95% CI, 0.62-1.45). The MTHFR 677TT genotype was associated with a significantly decreased risk of lung cancer in women (OR, 0.60; 95% CI, 0.40-0.92) but not in men. No association was found between the MTHFR G1793A polymorphism and risk of lung cancer. Further analysis suggested evidence of genedietary interactions between the MTHFR C677T polymorphism and dietary intake of vitamin B 6 , vitamin B 12 , and methionine in women and evidence of gene-environment interactions between the MTHFR C677T and A1298C polymorphisms and tobacco smoking in men. In conclusion, the polymorphisms of MTHFR may contribute to the risk of lung cancer in non-Hispanic Whites and modify the risk associated with the dietary and environmental exposure in a sex-specific manner. (Cancer Epidemiol Biomarkers Prev 2005;14(6):1477 -84)

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“…In fact, carriage of the 677T allele was associated with an elevated risk of developing esophageal (Song et al, 2001), gastric (Shen et al, 2001), ovarian (Gershoni-Baruch et al, 2000), and lung (Siemianowicz et al, 2003) cancer, and with a reduced risk in colorectal (Ma et al, 1997;Slattery et al, 1999;Yin et al, 2004) and lung (Jeng et al, 2003) cancer and in leukemia (Franco et al, 2001;Skibola et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

MTHFR C677T Polymorphism and Risk of HCC in Patients With Liver Cirrhosis: Role of Male Gender and Alcohol Consumption

Fabris

Toniutto

Falleti

et al. 2008

Alcoholism Clin & Exp Res

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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.

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Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms in patients with small cell and non-small cell lung cancer

Cited by 32 publications

References 0 publications

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and the risk of primary Hepatocellular Carcinoma (HCC) in a Chinese population

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and the risk of primary Hepatocellular Carcinoma (HCC) in a Chinese population

Sex Differences in Risk of Lung Cancer Associated with Methylene-tetrahydrofolate Reductase Polymorphisms

MTHFR C677T Polymorphism and Risk of HCC in Patients With Liver Cirrhosis: Role of Male Gender and Alcohol Consumption

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