Abstract

BackgroundThis study was designed to investigate an association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of lung cancer in a Korean population.MethodsWe conducted a large-scale, case-control study involving 3938 patients with newly diagnosed lung cancer and 1700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. Statistical significance was estimated by logistic regression analysis.ResultsThe MTHFR C677T frequencies of CC, CT, and TT genotypes were 34.5%, 48.5%, and 17% among lung cancer patients, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677CT and TT genotype showed a weak protection against lung cancer compared with the homozygous CC genotype, although the results did not reach statistical significance. The age- and gender-adjusted odds ratio (OR) of overall lung cancer was 0.90 (95% confidence interval (CI), 0.77-1.04) for MTHFR 677 CT and 0.88 (95% CI, 0.71-1.07) for MTHFR 677TT. However, after stratification analysis by histological type, the MTHFR 677CT genotype showed a significantly decreased risk for squamous cell carcinoma (age- and gender-adjusted OR, 0.78; 95% CI, 0.64-0.96). The combination of 677 TT homozygous with 677 CT heterozygous also appeared to have a protection effect on the risk of squamous cell carcinoma. We observed no significant interaction between the MTHFR C677T polymorphism and age and gender or smoking habit.ConclusionsThis is the first reported study focusing on the association between MTHFR C677T polymorphisms and the risk of lung cancer in a Korean population. The T allele was found to provide a weak protective association with lung squamous cell carcinoma.

Highlights

  • This study was designed to investigate an association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of lung cancer in a Korean population

  • The current study represents the largest sample (3938 lung cancer patients and 1700 controls) of a single population reported to evaluate a possible association between MTHFR C677T gene polymorphism and susceptibility to lung cancer

  • This is the first report to examine the association between MTHFR C677T polymorphisms and susceptibility to lung cancer in a Korean population

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Summary

Introduction

This study was designed to investigate an association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of lung cancer in a Korean population. According to the Korean National Cancer Registry, the age-standardized incidence rate for lung cancer of Korean population was 47.5/100,000 for men and 13.3/100,000 for women in 2007 [2], it has become the second most common malignant tumor following gastric cancer. The reason for this increase in lung cancer has not been clearly. The low enzymatic activity of the MTHFR C677T genotypic variant is associated with DNA hypomethylation, which may induce genomic instability or the derepression of proto-oncogenes

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