The Association Between Methylene-tetrahydrofolate Reductase Gene Polymorphism and Lung Cancer Risk

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2010 Jun 10

PMID 20532637

Citations 12

Authors

Sulhattin Arslan

Sule Karadayi

Malik Ejder Yildirim

Ozturk Ozdemir

Ibrahim Akkurt

Affiliations

Soon will be listed here.

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.

Citing Articles

Influence of polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility.

Huang Y, Hu Q, Wei Z, Chen L, Luo Y, Li X Open Life Sci. 2023; 18(1):20220680.

PMID: 37772262 PMC: 10523282. DOI: 10.1515/biol-2022-0680.

Folate/homocysteine metabolism and lung cancer risk among smokers.

Stanislawska-Sachadyn A, Borzyszkowska J, Krzeminski M, Janowicz A, Dziadziuszko R, Jassem J PLoS One. 2019; 14(4):e0214462.

PMID: 30939165 PMC: 6445430. DOI: 10.1371/journal.pone.0214462.

Genetic Variants Involved in One-Carbon Metabolism: Polymorphism Frequencies and Differences in Homocysteine Concentrations in the Folic Acid Fortification Era.

Steluti J, Carvalho A, Carioca A, Miranda A, Gattas G, Fisberg R Nutrients. 2017; 9(6).

PMID: 28587068 PMC: 5490518. DOI: 10.3390/nu9060539.

Meta-analysis on MTHFR polymorphism and lung cancer susceptibility in East Asian populations.

Zhang X, Li Y, Yang S, Li W Biomed Rep. 2014; 1(3):440-446.

PMID: 24648965 PMC: 3917083. DOI: 10.3892/br.2013.68.

Influence of methylenetetrahydrofolate reductase C677T polymorphism on the risk of lung cancer and the clinical response to platinum-based chemotherapy for advanced non-small cell lung cancer: an updated meta-analysis.

Zhu N, Gong Y, He J, Xia J, Chen X Yonsei Med J. 2013; 54(6):1384-93.

PMID: 24142642 PMC: 3809863. DOI: 10.3349/ymj.2013.54.6.1384.

References

Kelemen L, Anand S, Hegele R, Stampfer M, Rosner B, Willett W . Associations of plasma homocysteine and the methylenetetrahydrofolate reductase C677T polymorphism with carotid intima media thickness among South Asian, Chinese and European Canadians. Atherosclerosis. 2004; 176(2):361-70. DOI: 10.1016/j.atherosclerosis.2004.06.003. View

Parkin D, Pisani P, Ferlay J . Global cancer statistics. CA Cancer J Clin. 1999; 49(1):33-64, 1. DOI: 10.3322/canjclin.49.1.33. View

Xu W, Shrubsole M, Xiang Y, Cai Q, Zhao G, Ruan Z . Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women. Cancer Epidemiol Biomarkers Prev. 2007; 16(2):281-7. DOI: 10.1158/1055-9965.EPI-06-0798. View

Ergul E, Sazci A, Utkan Z, Canturk N . Polymorphisms in the MTHFR gene are associated with breast cancer. Tumour Biol. 2004; 24(6):286-90. DOI: 10.1159/000076460. View

Shen H, Wei Q, Pillow P, Amos C, Hong W, Spitz M . Dietary folate intake and lung cancer risk in former smokers: a case-control analysis. Cancer Epidemiol Biomarkers Prev. 2003; 12(10):980-6. View

Shields P . Molecular epidemiology of smoking and lung cancer. Oncogene. 2002; 21(45):6870-6. DOI: 10.1038/sj.onc.1205832. View

Shen H, Spitz M, Wang L, Hong W, Wei Q . Polymorphisms of methylene-tetrahydrofolate reductase and risk of lung cancer: a case-control study. Cancer Epidemiol Biomarkers Prev. 2001; 10(4):397-401. View

Heijmans B, Boer J, Suchiman H, Cornelisse C, Westendorp R, Kromhout D . A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased risk of cancer. Cancer Res. 2003; 63(6):1249-53. View

Spitz M, Wei Q, Dong Q, Amos C, Wu X . Genetic susceptibility to lung cancer: the role of DNA damage and repair. Cancer Epidemiol Biomarkers Prev. 2003; 12(8):689-98. View

10.

Frosst P, Blom H, Milos R, Goyette P, Sheppard C, Matthews R . A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995; 10(1):111-3. DOI: 10.1038/ng0595-111. View

11.

Raunio H, Husgafvel-Pursiainen K, Anttila S, Hietanen E, Hirvonen A, Pelkonen O . Diagnosis of polymorphisms in carcinogen-activating and inactivating enzymes and cancer susceptibility--a review. Gene. 1995; 159(1):113-21. DOI: 10.1016/0378-1119(94)00448-2. View

12.

Schabath M, Spitz M, Lerner S, Pillow P, Hernandez L, Delclos G . Case-control analysis of dietary folate and risk of bladder cancer. Nutr Cancer. 2006; 53(2):144-51. DOI: 10.1207/s15327914nc5302_3. View

13.

Choi S, Mason J . Folate status: effects on pathways of colorectal carcinogenesis. J Nutr. 2002; 132(8 Suppl):2413S-2418S. DOI: 10.1093/jn/132.8.2413S. View

14.

Siemianowicz K, Gminski J, Garczorz W, Slabiak N, Goss M, Machalski M . Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms in patients with small cell and non-small cell lung cancer. Oncol Rep. 2003; 10(5):1341-4. View

15.

Larsson S, Hakansson N, Giovannucci E, Wolk A . Folate intake and pancreatic cancer incidence: a prospective study of Swedish women and men. J Natl Cancer Inst. 2006; 98(6):407-13. DOI: 10.1093/jnci/djj094. View

16.

Song C, Xing D, Tan W, Wei Q, Lin D . Methylenetetrahydrofolate reductase polymorphisms increase risk of esophageal squamous cell carcinoma in a Chinese population. Cancer Res. 2001; 61(8):3272-5. View

17.

Perera F . Molecular epidemiology of environmental carcinogenesis. Recent Results Cancer Res. 1999; 154:39-46. DOI: 10.1007/978-3-642-46870-4_3. View

18.

Shrubsole M, Gao Y, Cai Q, Shu X, Dai Q, Hebert J . MTHFR polymorphisms, dietary folate intake, and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev. 2004; 13(2):190-6. DOI: 10.1158/1055-9965.epi-03-0273. View

19.

Spiro S, Porter J . Lung cancer--where are we today? Current advances in staging and nonsurgical treatment. Am J Respir Crit Care Med. 2002; 166(9):1166-96. DOI: 10.1164/rccm.200202-070SO. View

20.

Cheng Y, Hsieh L, Lin P, Chen C, Chen C, Lin T . Gender difference in DNA adduct levels among nonsmoking lung cancer patients. Environ Mol Mutagen. 2001; 37(4):304-10. DOI: 10.1002/em.1037. View