Research Papers:

Methylenetetrahydrofolate reductase tagging polymorphisms are associated with risk of non-small cell lung cancer in eastern Chinese Han population

Hao Ding, Yafeng Wang, Yuanmei Chen, Chao Liu, Hao Qiu, Mingqiang Kang and Weifeng Tang _

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Oncotarget. 2017; 8:110326-110336. https://doi.org/10.18632/oncotarget.22887

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Hao Ding1,*, Yafeng Wang2,*, Yuanmei Chen3,*, Chao Liu4, Hao Qiu5, Mingqiang Kang6 and Weifeng Tang6

1Department of Respiratory Disease, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China

2Department of Cardiology, The People's Hospital of Xishuangbanna Dai Autonomous Prefecture, Jinghong, Yunnan Province, China

3Department of Thoracic Surgery, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian Province, China

4Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China

5Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China

6Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China

*These authors contributed equally to this work

Correspondence to:

Weifeng Tang, email: [email protected]

Mingqiang Kang, email: [email protected]

Keywords: MTHFR; polymorphism; non-small cell lung cancer; risk

Received: May 30, 2017     Accepted: November 08, 2017     Published: December 04, 2017


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.

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