Skip to main content

Advertisement

Log in

The association between methylene-tetrahydrofolate reductase gene polymorphism and lung cancer risk

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

This study aimed to determine the relation between methylene-tetrahydrofolate reductase (MTHFR) gene polymorphism and lung cancer risk and the frequency of this polymorphism. The study involved 64 lung cancer patients (the study group) with definitive diagnosis and 61 noncancerous subjects (the control group). MTHFR C677T and A1298C mutation analysis was made using DNA isolated from peripheric blood and multiplex PCR and reverse hybridization strip test. Eighty-four percent of the patients were male. The age, gender, and history of alcohol use of the patients and control group were statistically similar. While MTHFR 677T and 677C allele frequency was 0.33 and 0.67 in the patients respectively, it was 0.29 and 0.71 in the control group. The frequencies of MTHFR 1298C and 1298A were 0.33 and 0.67 in the patients, and it was 0.31 and 0.69 in the control group respectively. When MTHFR 677TT and 677CT genotypes were compared with 677CC genotype, lung cancer risk was 2.4 times higher in the 677TT genotype. When MTHFR 1298AC and 1298CC genotypes were compared with 1298AA genotype, lung cancer risk was 1.5 times higher in 1298CC genotype. According to the results, allele frequency of homozygote T and C was high in lung cancer patients. It was 3.05 and 1.29 times higher in smokers than in non-smokers, and 3.05 and 1.64 times higher in males than in females; 3.0 and 2.44 times higher in those with non-small cell lung cancer than in those with small-cell lung cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Spiro SG, Porter JC (2002) Lung cancer—where are we today? Current advances in staging and nonsurgical treatment. Am J Respir Crit Care Med 166:1166–1196

    Article  PubMed  Google Scholar 

  2. Parkin GM, Pisani P, Ferlay J (1999) Global cancer statistics. CA Cancer J Clin 49:33–64

    Article  CAS  PubMed  Google Scholar 

  3. Postmus PE (1998) Epidemiology of lung cancer. In: Fishman AP, Elias JA, Fishman JA et al (eds) Fishman’s pulmonary diseases and disorders. McGraw Hill Companies, New York, pp 1707–1719

    Google Scholar 

  4. Shields PG (2002) Molecular epidemiology of smoking and lung cancer. Oncogene 21:6870–6876

    Article  CAS  PubMed  Google Scholar 

  5. Spitz MR, Wei Q, Dong Q, Amos CI, Wu X (2003) Genetic susceptibility to lung cancer: the role of DNA damage and repair. Cancer Epidemiol Biomarkers Prev 12:689–698

    CAS  PubMed  Google Scholar 

  6. World Cancer Research Fund, American Institute for Cancer Research Expert Panel (Potter JD, chair) (1997) Food, nutrition and the prevention of cancer: a global perspective. American Institute for Cancer Research, Washington (DC)

  7. Perera FP (1998) Molecular epidemiology of environmental carcinogenesis. Recent Results Cancer Res 154:39–46

    CAS  PubMed  Google Scholar 

  8. Raunio H, Husgafvel-Pursiainen K, Anttila S, Hietanen E, Hirvonen A, Pelkonen O (1995) Diagnosis of polymorphisms in carcinogen activating and inactivating enzymes and cancer susceptibility. Gene 159:113–121

    Article  CAS  PubMed  Google Scholar 

  9. Shen H, Wei Q, Pillow PC, Amos CI, Hong WK, Spitz MR (2003) Dietary folate intake and lung cancer risk in former smokers: a case control analysis. Cancer Epidemiol Biomarkers Prev 12:980–986

    CAS  PubMed  Google Scholar 

  10. Larsson SC, Håkansson N, Giovannucci E, Wolk A (2006) Folate intake and pancreatic cancer incidence: a prospective study of Swedish women and men. J Natl Cancer Inst 98(6):407–413

    Article  CAS  PubMed  Google Scholar 

  11. Schabath MB, Spitz MR, Lerner SP, Pillow PC, Hernandez LM, Delclos GL, Grossman HB, Wu X (2005) Case-control analysis of dietary folate and risk of bladder cancer. Nutr Cancer 53(2):144–151

    Article  CAS  PubMed  Google Scholar 

  12. Shrubsole MJ, Gao YT, Cai Q, Shu XO, Dai Q, Hébert JR, Jin F, Zheng W (2004) MTHFR polymorphisms, dietary folate intake, and breast cancer risk: results from the Shanghai breast cancer study. Cancer Epidemiol Biomarkers Prev 13:190–196

    Article  CAS  PubMed  Google Scholar 

  13. Choi SW, Mason JB (2002) Folate status: effects on pathways of colorectal carcinogenesis. J Nutr 132:2413–2418

    Google Scholar 

  14. Xu WH, Shrubsole MJ, Xiang YB, Cai Q, Zhao GM, Ruan ZX, Cheng JR, Zheng W, Shu XO (2007) Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese woman. Cancer Epidemiol Biomarkers Prev 16(2):281–287

    Article  CAS  PubMed  Google Scholar 

  15. Heijmans BT, Boer JMA, Suchiman HED, Cornelisse CJ, Westendorp RGJ, Kromhout D, Feskens EJM, Slagboom PE (2003) A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased risk of cancer. Cancer Res 63:1249–1253

    CAS  PubMed  Google Scholar 

  16. Leclerc D, Sibani S, Rosen R (2005) Molecular biology of methylenetetrahydrofolate reductase (MTHFR) and overview of mutations/polymorphisms. In: Ueland PM, Rozen R (eds) MTHFR polymorphisms and disease. Landes Bioscience, Texas, USA, pp 1–20

    Google Scholar 

  17. Robien K, Ulrich CM (2003) 5, 10-Methylenetetrahydrofolate reductase polymorphisms and leukemia risk: a HuGE minireview. Am J Epidemiol 157:571–582

    Article  PubMed  Google Scholar 

  18. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJH, den Heijer M, Kluijtmans LAJ, van den Heuve LP, Rozen R (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111–113

    Article  CAS  PubMed  Google Scholar 

  19. Weisberg I, Tran P, Christensen B, Sibani S, Rozen R (1998) A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 64:169–172

    Article  CAS  PubMed  Google Scholar 

  20. Ergul E, Sazci A, Utkan Z, Canturk NZ (2003) Polymorphisms in the MTHFR gene are associated with breast cancer. Tumour Biol 24:286–290

    Article  CAS  PubMed  Google Scholar 

  21. Stolzenberg-Solomon RZ, Qiao YL, Abnet CC, Ratnasinghe DL, Dawsey SM, Dong ZW, Taylor PR, Mark SD (2003) Esophageal and gastric cardia cancer risk and folate- and vitamin B (12)-related polymorphisms in Linxian, China. Cancer Epidemiol Biomarkers Prev 12:1222–1226

    CAS  PubMed  Google Scholar 

  22. Song C, Xing D, Tan W, Wei Q, Lin D (2001) Methylenetetrahydrofolate reductase polymorphisms increase risk of esophageal squamous cell carcinoma in a Chinese population. Cancer Res 61:3272–3275

    CAS  PubMed  Google Scholar 

  23. Siemianowicz K, Gminski J, Garczorz W, Slabiak N, Goss M, Machalski M, Magiera-Molendowska H (2003) Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms in patients with small cell and non-small cell lung cancer. Oncol Rep 10:1341–1344

    CAS  PubMed  Google Scholar 

  24. Shen H, Spitz MR, Wang LE, Hong WK, Wei Q (2001) Polymorphisms of methylene-tetrahydrofolate reductase and risk of lung cancer: a case-control study. Cancer Epidemiol Biomarkers Prev 10:397–401

    CAS  PubMed  Google Scholar 

  25. Jeng YL, Wu MH, Huang HB, Lin WY, You SL, Chu TY, Chen CJ (2003) The methylenetetrahydrofolate reductase 677C → T polymorphism and lung cancer risk in a Chinese population. Anticancer Res 23:5149–5152

    CAS  PubMed  Google Scholar 

  26. Shi Q, Zhang Z, Li G, Pillow PC, Hernandez LM, Spitz MR, Wei Q (2005) Sex differences in risk of lung cancer associated with methylene-tetrahydrofolate reductase polymorphisms. Cancer Epidemiol Biomarkers Prev 14(6):1477–1484

    Article  CAS  PubMed  Google Scholar 

  27. Suzuki T, Matsuo K, Hiraki A, Saito T, Sato S, Yatabe Y, Mitsudomi M, Hida T, Ueda R, Tajima K (2007) Impact of one-carbon metabolism-related gene polymorphisms on risk of lung cancer in Japan: a case–control study. Carcinogenesis 28(8):1718–1725

    Google Scholar 

  28. Ryberg D, Hewer A, Phillips DH, Haugen A (1994) Different susceptibility to smoking-induced DNA damage among male and female lung cancer atients. Cancer Res 54:5801–5803

    CAS  PubMed  Google Scholar 

  29. Mollerup S, Ryberg D, Hewer A, Phillips DH, Haugen A (1999) Sex differences in lung CYP1A1 expression and DNA adduct levels among lung cancer patients. Cancer Res 59:3317–3320

    CAS  PubMed  Google Scholar 

  30. Cheng YW, Hsieh LL, Lin PP, Chen CP, Chen CY, Lin TS, Su SM (2001) Gender difference in DNA adduct levels among nonsmoking lung cancer patients. Environ Mol Mutagen 37:304–310

    Article  CAS  PubMed  Google Scholar 

  31. Kelemen LE, Anand SS, Hegele RA, Stampferef MJ, Rosnerf B, Willettef WC, Montague PA (2004) Associations of plasma homocysteine and the methylenetetrahydrofolate reductase C677T polymorphism with carotid intima media thickness among South Asian, Chinese and European Canadians. Atherosclerosis 176:361–370

    Article  CAS  PubMed  Google Scholar 

  32. Curtin K, Bigler J, Slattery ML, Caan B, Potter JD, Ulrich CM (2004) MTHFR C677T and A1298C polymorphisms: diet, estrogen, and risk of colon cancer. Cancer Epidemiol Biomarkers Prev 13:285–292

    Article  CAS  PubMed  Google Scholar 

  33. Gemmati D, Ongaro A, Scapoli GL, Porta MD, Tognazzo S, Serino ML, Bona ED (2004) Common gene polymorphisms in the metabolic folate and methylation pathway and the risk of acute lymphoblastic leukemia and non Hodgkin’s lymphoma in adults. Cancer Epidemiol Biomarkers Prev 13:787–794

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sule Karadayi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arslan, S., Karadayi, S., Yildirim, M.E. et al. The association between methylene-tetrahydrofolate reductase gene polymorphism and lung cancer risk. Mol Biol Rep 38, 991–996 (2011). https://doi.org/10.1007/s11033-010-0194-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-010-0194-z

Keywords

Navigation