Article

Alcohol Consumption and Genetic Variation in Methylenetetrahydrofolate Reductase and 5-Methyltetrahydrofolate-Homocysteine Methyltransferase in Relation to Breast Cancer Risk

Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.32). 09/2009; 18(9):2453-9. DOI: 10.1158/1055-9965.EPI-09-0159
Source: PubMed

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.

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    • "Thus, women with the TT genotype are at a higher risk of breast cancer than those with other genotypes. In postmenopausal women, the breast cancer risk was increased in women with the C677T MTHFR variant who had high lifetime daily alcohol intake, suggesting that folate metabolism has an impact on cancer development (Platek et al. 2009). As mentioned earlier, chronic alcohol abuse can cause folate deficiency, which is a well-documented risk factor for breast cancer (Sellers et al. 2001). "
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    • "Overall (I-squared = 60.7%, p = 0.000) Mohammad 2011 Cam 2009 Cheng 2008 Subtotal (I-squared = 33.8%, p = 0.052) Fo¡ §rsti 2004 Langsenlehner 2008 Justenhoven 2005 Platek 2009 Xu 2007 Chen 2005 Prasad 2011 Ericson 2009 Mixed Caucasian Batschauer 2011 Langsenlehner 2003 Qi 2004 Alshatwi 2010 Barbosa 2012 Yuan 2009 Sangrajrang 2010 Suzuki 2008 Bentley 2010 Study Deligezer 2005 Subtotal (I-squared = 53.5%, p = 0.003) Subtotal (I-squared = 85.3%, p = 0.000) Kalemi 2005 Lin 2004 Chou 2006 Ergul 2003 Weiner 2010 Gao 2009 Semenza 2003 Lajin 2012 Akram 2012 Cerne 2011 ID Asian Sharp 2002 Naushad 2011 Maruti 2009 Jakubowska 2012 Jin 2009 Inoue 2008 Macis 2007 Henr¡äquez-Herna¡ändez 2009 Kalyankumar 2006 Hekim 2007 Lee 2004 Reljic 2007 Shrubsole 2004 Ma 2009 Ma 2009 Kotsopoulos 2008 Campbell 2002 Grieu 2004 Yu 2007 Li 2009 "
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    ABSTRACT: The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been widely reported, but results were inconsistent and underpowered. To clarify the effects of MTHFR polymorphisms on the risk of breast cancer, an updated meta-analysis of all available studies relating C677T and/or A1298C polymorphisms of MTHFR gene to the risk of breast cancer was conducted. Eligible articles were identified by search of databases including MEDLINE, PubMed, Web of Science, EMBASE and Chinese Biomedical Literature database (CBM) for the period up to January 2010. Finally, a total of 41 studies with 16,480 cases and 22,388 controls were included, all for C677T polymorphism and 20 with 12,170 cases and 15,865 controls for A1298C polymorphism. The pooled ORs were performed for the allele contrasts, additive genetic model, dominant genetic model, and recessive genetic model, respectively. Subgroup analyses were also performed by ethnicity and menopausal status. With respect to C677T polymorphism, significantly elevated breast cancer risk was found in overall analysis (T vs. C: OR = 1.041, 95% CI = 1.009-1.073; TT vs. CC: OR = 1.132, 95% CI = 1.019-1.259; TT vs. CC + CT: OR = 1.119, 95% CI = 1.014-1.236); in the subgroup analysis by ethnicity, significantly increased risk was found in East Asian population (T vs. C: OR = 1.121, 95% CI = 1.016-1.237; TT vs. CC: OR = 1.331, 95% CI = 1.073-1.650; TT vs. CC + CT: OR = 1.265, 95% CI = 1.058-1.513) but not in Caucasian population; in the subgroup analysis by menopausal status, no statistically significant association was found. With respect to A1298C polymorphism, no significant association with breast cancer risk was demonstrated in overall, ethnicity- and menopausal status-based population. It can be concluded that potentially functional MTHFR C677T polymorphism may play a low penetrance role in the development of breast cancer.
    Breast Cancer Research and Treatment 02/2010; 123(2):499-506. DOI:10.1007/s10549-010-0773-7 · 4.20 Impact Factor
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