Abstract
Previous reports implicated 5,10-ethylenetetrahydrofolate reductase (MTHFR) polymorphisms acted as a potential risk factor for several cancers. In order to explore the effect of MTHFR SNPs on non-small cell lung cancer (NSCLC), we selected MTHFR tagging single nucleotide polymorphisms (SNPs) and carried out a case-control study to determine the potential relationship of MTHFR SNPs with NSCLC risk. Our study consisted of 521 NSCLC patients and 1,030 non-cancer controls. MTHFR SNPs were genotyped by SNPscanTM genotyping assay. Using four genetic models (additive, Homozygote, dominant, recessive), the genotype frequencies were compared using the chi-squared (χ2) test. Crude/adjusted odds ratios (ORs) with their 95% confidence intervals (CIs) were used to assess the difference for the genotype distribution. We found that MTHFR rs1801133 G>A polymorphism decreased the risk of overall NSCLC. In a subgroup analysis, MTHFR rs1801133 G>A polymorphism also decreased NSCLC risk in female, < 60 years and never smoking subgroups. However, we identified that MTHFR rs4845882 G>A polymorphism was associated with the development of NSCLC in female subgroup. In addition, MTHFR rs9651118 T>C polymorphism increased the risk of NSCLC in < 60 years, never smoking and BMI < 24 kg/m2 subgroups. In conclusion, the current study highlights MTHFR rs1801133 G>A variants decreases the risk of NSCLC. Nevertheless, MTHFR rs4845882 G>A and rs9651118 T > C polymorphisms may be associated with NSCLC susceptibility. Well-designed large-scale studies are needed to confirm these findings and explore the interactions of gene-gene and gene-environment involved in MTHFR SNPs and NSCLC.
Highlights
Lung cancer (LC) caused by multiple risk factors is one of the common malignancies worldwide
After adjustment by logistic regression analysis, we found MTHFR rs1801133 G>A variants were associated with the decreased risk of non-small cell LC (NSCLC) in some subgroups
We found that MTHFR rs9651118 T>C polymorphism increased the risk of NSCLC in several stratified analyses
Summary
Lung cancer (LC) caused by multiple risk factors is one of the common malignancies worldwide. With very complex biological characteristics and high degree of invasiveness, it is difficult to diagnose at an early stage and lack of very effective treatment at an advanced stage. LC is a common public health problem with a poor www.impactjournals.com/oncotarget prognosis. The increasing incidence of NSCLC is closely related to tobacco consumption, air pollution, cooking fumes, asbestos and other environmental factors [1]. These known risk factors might not contribute to overall susceptibility to NSCLC. Individual’s genetic factors have been determined to cause NSCLC
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