Objective: To examine the relationship between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR ) gene and susceptibility to lung cancer in a female Chinese population.
Method: A hospital-based case-control study of 388 cases and 388 controls was conducted. Two polymorphisms in MTHFR  were detected using TaqMan methods.
Results: The MTHFR  C677T polymorphism was associated with the risk of lung cancer and lung adenocarcinoma. Carriers with the TT genotype of C677T were observed to have an increased risk of lung cancer and lung adenocarcinoma (the ORs were 1.550 and 1.588, respectively). By contrast, the A1298C polymorphism had a negative relationship with the risk of lung cancer and lung adenocarcinoma; compared with the AA genotype carriers, the CC genotype carriers had a lower risk of lung cancer and adenocarcinoma in the female Chinese population (ORs were 0.302 and 0.215, respectively). In the stratified analyses, we observed only the A1298C polymorphism in the CC genotype carriers with a statistically significant reduction in the risk of non-small-cell lung cancer, compared to the AA genotype carriers. No significant statistical association was found between the MTHFR  gene polymorphisms and risk of the residual subtype of lung cancer.
Conclusion: This study provides evidence that the MTHFR  C677T polymorphism may contribute to the development of lung cancer and lung adenocarcinoma in a female Chinese population. However, the MTHFR  A1298C polymorphism may be associated with the decreasing risk of lung cancer.
Keywords: MTHFR , single nucleotide polymorphism, lung cancer, genetic susceptibility