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Polymorphisms of methylene-tetrahydrofolate reductase and risk of lung cancer: a case-control study.
Cancer Epidemiol Biomarkers Prev 2001; 10(4):397-401CE

Abstract

Previous studies have suggested that low folate intake is associated with increased risk of lung cancer. Methylene-tetrahydrofolate reductase (MTHFR) is one of the enzymes involved in folate metabolism and is thought to influence DNA methylation and nucleotide synthesis. MTHFR is highly polymorphic, and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. Therefore, we hypothesized that these variant genotypes may play a role in the etiology of lung cancer. To test this hypothesis, we investigated the association between two common MTHFR polymorphisms (C677T and A1298C) and risk of lung cancer in a non-population-based case-control study of 550 histologically confirmed lung cancer cases and 554 healthy controls. The subjects were non-Hispanic whites, and the controls were frequency-matched to the cases by age (+ or -5 years), sex, and smoking status (ever or never). Folate intake and alcohol consumption were estimated from a self-administered food-frequency questionnaire. The cases consumed significantly less folate (162 microg/day/1000 kcal) than the controls did (172 microg/day/1000 kcal; P = 0.033). However, we found no evidence for an association between the MTHFR C677T and A1298C polymorphisms and risk of lung cancer in either all of the subjects or the low folate intake subgroup; nor did we find evidence for an interaction between these two MTHFR polymorphisms and dietary folate intake or alcohol use. In multivariate logistic regression analysis, the adjusted odds ratios and 95% confidence intervals for MTHFR C677T were 1.1 (0.8-1.4) for 677CT versus 677CC wild type and 1.1 (0.7-1.7) for 677TT versus 677CC, and for MTHFR A1298C, they were 1.0 (0.8-1.3) for 1298AC versus 1298AA wild type and 1.1 (0.7-1.8) for 1298CC versus 1298AA. These results suggest that the MTHFR C677T and A1298C polymorphisms by themselves do not play an important role in the etiology of lung cancer.

Authors+Show Affiliations

Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11319182

Citation

Shen, H, et al. "Polymorphisms of Methylene-tetrahydrofolate Reductase and Risk of Lung Cancer: a Case-control Study." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 10, no. 4, 2001, pp. 397-401.
Shen H, Spitz MR, Wang LE, et al. Polymorphisms of methylene-tetrahydrofolate reductase and risk of lung cancer: a case-control study. Cancer Epidemiol Biomarkers Prev. 2001;10(4):397-401.
Shen, H., Spitz, M. R., Wang, L. E., Hong, W. K., & Wei, Q. (2001). Polymorphisms of methylene-tetrahydrofolate reductase and risk of lung cancer: a case-control study. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 10(4), pp. 397-401.
Shen H, et al. Polymorphisms of Methylene-tetrahydrofolate Reductase and Risk of Lung Cancer: a Case-control Study. Cancer Epidemiol Biomarkers Prev. 2001;10(4):397-401. PubMed PMID: 11319182.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polymorphisms of methylene-tetrahydrofolate reductase and risk of lung cancer: a case-control study. AU - Shen,H, AU - Spitz,M R, AU - Wang,L E, AU - Hong,W K, AU - Wei,Q, PY - 2001/4/25/pubmed PY - 2001/8/10/medline PY - 2001/4/25/entrez SP - 397 EP - 401 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol. Biomarkers Prev. VL - 10 IS - 4 N2 - Previous studies have suggested that low folate intake is associated with increased risk of lung cancer. Methylene-tetrahydrofolate reductase (MTHFR) is one of the enzymes involved in folate metabolism and is thought to influence DNA methylation and nucleotide synthesis. MTHFR is highly polymorphic, and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. Therefore, we hypothesized that these variant genotypes may play a role in the etiology of lung cancer. To test this hypothesis, we investigated the association between two common MTHFR polymorphisms (C677T and A1298C) and risk of lung cancer in a non-population-based case-control study of 550 histologically confirmed lung cancer cases and 554 healthy controls. The subjects were non-Hispanic whites, and the controls were frequency-matched to the cases by age (+ or -5 years), sex, and smoking status (ever or never). Folate intake and alcohol consumption were estimated from a self-administered food-frequency questionnaire. The cases consumed significantly less folate (162 microg/day/1000 kcal) than the controls did (172 microg/day/1000 kcal; P = 0.033). However, we found no evidence for an association between the MTHFR C677T and A1298C polymorphisms and risk of lung cancer in either all of the subjects or the low folate intake subgroup; nor did we find evidence for an interaction between these two MTHFR polymorphisms and dietary folate intake or alcohol use. In multivariate logistic regression analysis, the adjusted odds ratios and 95% confidence intervals for MTHFR C677T were 1.1 (0.8-1.4) for 677CT versus 677CC wild type and 1.1 (0.7-1.7) for 677TT versus 677CC, and for MTHFR A1298C, they were 1.0 (0.8-1.3) for 1298AC versus 1298AA wild type and 1.1 (0.7-1.8) for 1298CC versus 1298AA. These results suggest that the MTHFR C677T and A1298C polymorphisms by themselves do not play an important role in the etiology of lung cancer. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/11319182/Polymorphisms_of_methylene_tetrahydrofolate_reductase_and_risk_of_lung_cancer:_a_case_control_study_ L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11319182 DB - PRIME DP - Unbound Medicine ER -