MTHFR C667T Polymorphism Association with Lung Cancer Risk in Henan Province: A Case-control Study

  • Cheng, Zhe (Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Institute of Clinical Medical Research of Henan Universities) ;
  • Wang, Wei (Department of Occupational Health and Toxicology, School of Public Health, Zhengzhou University) ;
  • Dai, Ling-Ling (Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Institute of Clinical Medical Research of Henan Universities) ;
  • Kang, Yan (Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Institute of Clinical Medical Research of Henan Universities)
  • Published : 2012.06.30


The current study was performed to assess any association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and risk of lung cancer in Henan province. This case-control study involved94 patients with newly histological confirmed lung cancer and 78 healthy controls. Genotyping was achieved with peripheral blood lymphocytes DNA and association of the polymorphism with risk of lung cancer was estimated by unconditional logistic regression analysis. The frequencies of the MTHFR 667TT genotype were 37.2% in cases compared with 23.1% in controls (${\chi}^2$ = 4.008, P = 0.045). Individuals with the 667CC/CT genotype displayed a significantly reduced risk of lung cancer compared with those with the TT genotypes [adjusted odds ratio (OR), 0.506; 95% confidence interval (95% CI), 0.258 - 0.991]. The C667T polymorphism might have a significant effect on the occurrence of lung cancer in Henan province.


  1. Amos CI, Wu XF, Broderick P, et al (2008). Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nature Genetics, 40, 616-22.
  2. Arslan S, Karadayi S, Yildirim ME, Ozdemir O, Akkurt I (2011). The association between methylene-tetrahydrofolate reductase gene polymorphism and lung cancer risk. Mol Biol Rep, 38, 991-6.
  3. Boccia S, Boffetta P, Brennan P, et al (2009). Meta-analyses of the methylenete trahydrofolate reductase C677T and A1298C polymorphisms and risk of head and neck and lung cancer. Cancer Lett, 273, 55-61.
  4. Botto LD, Yang Q (2000). 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol, 151, 862-77.
  5. Cui LH, Shin MH, Kim HN, et al (2011). Methylenetetrahydrofolate reductase C677T polymorphism in patients with lung cancer in a Korean population. BMC Med Genet, 22, 12-28.
  6. Dong LM, Potter JD, White E, et al (2008). Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA, 299, 2423-36.
  7. Eaton AM, Sandler R, Carethers JM, et al (2005). 5,10-methylenetetrahydrofolate reductase 677 and 1298 polymorphisms, folate intake, and microsatellite instability in colon cancer. Cancer Epidemiol Biomarkers Prev, 14, 2023-9.
  8. Friso S, Choi SW (2005). Gene-nutrient interactions in onecarbon metabolism. Curr Drug Metab, 6, 37-46.
  9. Frosst P, Blom HJ, Milos R, et al (1995). A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature genetics, 10, 111-3.
  10. Gill P (2001). An assessment of the utility of single nucleotide polymorphisms (SNPs) for forensic purposes. Int J Legal Med, 114, 204-10.
  11. Guenther BD, Sheppard CA, Tran P, et al (1999). The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia. Nat Struct Biol, 6, 359-65.
  12. Hoekstra HE, Hirschmann RJ, Bundey RA, Insel PA, Crossland JP (2006). A single amino acid mutation contributes to adaptive beach mouse color pattern. Science, 313, 101-4.
  13. Hung RJ, Hashibe M, McKay J, et al (2007). Folate-related genes and the risk of tobacco-related cancers in Central Europe. Carcinogenesis, 28, 1334-40.
  14. Jemal A, Siegel R, Xu J, Ward F (2010). Cancer statistics, 2010. CA Cancer J Clin, 60, 277-300.
  15. Jin C, Zhang YH, Peng MF, et al (2007). Research of relationship between gene polymorphisms of methylenetetrahydrofolate reductase enzyme and lung cancer. Chin J Cancer Prevention and Treatment, 14, 888-91.
  16. Jeng YL, Wu MH, Huang HB, et al (2003). The methylenetetrahydrofolate reductase 677C-->T polymorphism and lung cancer risk in a Chinese population. Anticancer Res, 23, 5149-52.
  17. Li D, Ahmed M, Li Y, Jiao L, et al (2005). 5, 10 - Methylenetetrahydrofolate reductase polymorphisms and the risk of pancreatic cancer. Cancer Epidemiol Biomarkers Prev, 14, 1470-6.
  18. Li D, Pickell L, Liu Y, et al (2005). Maternal methylenetetrahydrofolate reductase deficiency and low dietary folate lead to adverse reproductive outcomes and congenital heart defects in mice. Am J Clin Nutr, 82, 188-95.
  19. Lin J, Spitz MR, Wang Y, et al (2004). Polymorphisms of folate metabolic genes and susceptibility to bladder cancer: a casecontrol study. Carcinogenesis, 25, 1639-47.
  20. Liu CS, Tsai CW, Hsia TC, et al (2009). Interaction of methylenetetrahydrofolate reductase genotype and smoking habit in Taiwanese lung cancer patients. Cancer Genomics Proteomics, 6, 325-9.
  21. Mao R, Fan Y, Jin Y, Bai J, Fu S (2008). Methy-lenetetrahydrofolate reductase gene polymorphisms and lung cancer: a metaanalysis. J Hum Genet, 53, 340-8.
  22. Matsuo K, Suzuki R, Hamajima N, et al (2001). Association between polymorphisms of folate- and methioninemetabolizing enzymes and susceptibility to malignant lymphoma. Blood, 97, 3205-9.
  23. Pepe G, Camacho Vanegas O, et al (1998). Heterogeneity in world distribution of the thermolabile C677T mutation in 5,10-methylenetetrahydrofolate reductase. Am J Hum Genet, 63, 917-20.
  24. Poehlmann A, Kuester D, Meyer F, et al (2007). K-ras mutation detection in colorectal cancer using the Pyrosequencing technique. Pathol Res Pract, 203, 489-97.
  25. Shen M, Rothman N, Berndt SI, et al (2005). Polymorphisms in folate metabolic genes and lung cancer risk in Xuan Wei, China. Lung Cancer, 49, 299-309.
  26. Shields PG (2002). Molecular epidemiology of smoking and lung cancer. Oncogene, 21, 6870-6.
  27. Shi Q, Zhang Z, Li G, et al (2005). Sex differences in risk of lung cancer associated with methylene-tetrahydrofolate reductase polymorphisms. Cancer Epidemiol Biomarkers Prev, 14, 1477-84.
  28. Siemianowicz K, Gminski J, Garczorz W, et al (2003). Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms in patients with small cell and nonsmall cell lung cancer. Oncol Rep, 10, 1341-4.
  29. Suzuki T, Matsuo K, Hiraki A, et al (2007). Impact of onecarbon metabolism-related gene polymorphisms on risk of lung cancer in Japan: a case control study. Carcinogenesis, 28, 1718-25.
  30. Yu JM, Wang XC, Chen BB, et al (1998). The Various of Methylenetetrahydrofolate reductase gene polymorphism in five Chinese ethnic. Human Science, 17, 242-6.

Cited by

  1. Lack of Association between the MTHFR C677T Polymorphism and Lung Cancer in a Turkish Population vol.15, pp.15, 2014,
  2. Allele and Genotype Frequencies of the Polymorphic Methylenetetrahydrofolate Reductase and Lung Cancer in ther Jordanian Population: a Case Control Study vol.16, pp.8, 2015,