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Alcohol consumption and genetic variation in methylenetetrahydrofolate reductase and 5-methyltetrahydrofolate-homocysteine methyltransferase in relation to breast cancer risk.

ABSTRACT: It has been hypothesized that effects of alcohol consumption on one-carbon metabolism may explain, in part, the association of alcohol consumption with breast cancer risk. The methylenetetrahydrofolate reductase (MTHFR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) genes express key enzymes in this pathway. We investigated the association of polymorphisms in MTHFR (rs1801133 and rs1801131) and MTR (rs1805087) with breast cancer risk and their interaction with alcohol consumption in a case-control study--the Western New York Exposures and Breast Cancer study. Cases (n = 1,063) were women with primary, incident breast cancer and controls (n = 1,890) were frequency matched to cases on age and race. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression. We found no association of MTHFR or MTR genotype with risk of breast cancer. In the original case-control study, there was a nonsignificant increased odds of breast cancer among women with higher lifetime drinking. In the current study, there was no evidence of an interaction of genotype and alcohol in premenopausal women. However, among postmenopausal women, there was an increase in breast cancer risk for women who were homozygote TT for MTHFR C677T and had high lifetime alcohol intake (>or=1,161.84 oz; OR, 1.92; 95% CI, 1.13-3.28) and for those who had a high number of drinks per drinking day (>1.91 drinks/day; OR, 1.80; 95% CI, 1.03-3.28) compared with nondrinkers who were homozygote CC. Our findings indicate that among postmenopausal women, increased breast cancer risk with alcohol consumption may be as a result of effects on one-carbon metabolism.

SUBMITTER: Platek ME

PROVIDER: S-EPMC2941988 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Alcohol consumption and genetic variation in methylenetetrahydrofolate reductase and 5-methyltetrahydrofolate-homocysteine methyltransferase in relation to breast cancer risk.

Platek Mary E ME Shields Peter G PG Marian Catalin C McCann Susan E SE Bonner Matthew R MR Nie Jing J Ambrosone Christine B CB Millen Amy E AE Ochs-Balcom Heather M HM Quick Sylvia K SK Trevisan Maurizio M Russell Marcia M Nochajski Thomas H TH Edge Stephen B SB Freudenheim Jo L JL

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20090825 9

It has been hypothesized that effects of alcohol consumption on one-carbon metabolism may explain, in part, the association of alcohol consumption with breast cancer risk. The methylenetetrahydrofolate reductase (MTHFR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) genes express key enzymes in this pathway. We investigated the association of polymorphisms in MTHFR (rs1801133 and rs1801131) and MTR (rs1805087) with breast cancer risk and their interaction with alcohol consumpt ...[more]

PMID: 19706843

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Project description:BackgroundCigarette smoking is an established risk factor of lung cancer development while the current epidemiological evidence is suggestive of an increased lung cancer risk associated with alcohol consumption. Dietary folate, which is present in a wide range of fresh fruits and vegetables, may be a micronutrient that has a beneficial impact on lung carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating folate metabolism, which affects both DNA synthesis/repair and methylation. We examined if smoking or alcohol consumption modify associations between MTHFR polymorphisms and lung cancer risk.MethodsWe evaluated the role of the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI).ResultsThe TT genotype of the C677T polymorphism was significantly associated with an increased risk of lung cancer (OR = 2.27, 95% CI = 1.42 - 3.62, P < 0.01) while the A1298C polymorphism was not associated with lung cancer risk. The minor alleles of both polymorphisms behaved in a recessive fashion. The highest risks were seen for 677TT-carriers with a history of smoking or excessive drinking (OR = 6.16, 95% CI = 3.48 - 10.9 for smoking; OR = 3.09, 95% CI = 1.64 - 5.81 for drinking) compared with C-carriers without a history of smoking or excessive drinking, but no interactions were seen. The 1298CC genotype was only associated with increased risk among non-smokers (P < 0.05), and smoking was only associated with increased risks among 1298A-carriers (P < 0.01), but no significant interaction was seen. There was a synergistic interaction between the A1298C polymorphism and drinking (P < 0.05). The highest risk was seen for the CC-carriers with excessive drinking (OR = 7.24, 95% CI = 1.89 - 27.7) compared with the A-carriers without excessive drinking).ConclusionsThe C677T polymorphism was significantly associated with lung cancer risk. Although the A1298C polymorphism was not associated with lung cancer risk, a significant interaction with drinking was observed. Future studies incorporating data on folate intake may undoubtedly lead to a more thorough understanding of the role of the MTHFR polymorphisms in lung cancer development.

Dataset Information

Alcohol consumption and genetic variation in methylenetetrahydrofolate reductase and 5-methyltetrahydrofolate-homocysteine methyltransferase in relation to breast cancer risk.

Publications

Alcohol consumption and genetic variation in methylenetetrahydrofolate reductase and 5-methyltetrahydrofolate-homocysteine methyltransferase in relation to breast cancer risk.

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