Carcinogenesis Advance Access originally published online on July 13, 2005
Carcinogenesis 2005 26(12):2131-2137; doi:10.1093/carcin/bgi179
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Carcinogenesis Vol.26 No.12 © Oxford University Press 2005; all rights reserved.
MGMT genotype modulates the associations between cigarette smoking, dietary antioxidants and breast cancer risk
1 Department of Environmental Health Sciences and 2 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA, 3 Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA and 4 Department of Community and Preventive Medicine, Mt Sinai School of Medicine, New York, NY 10029, USA
* To whom requests for reprints should be addressed at: 701 West, 168th Street, Room 505, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. Tel: +1 212 305 8158; Fax: +1 212 305 5328; Email: js2182{at}columbia.edu
O6-methylguanine DNA methyl-transferase (MGMT) is the only known critical gene involved in cellular defense against alkylating agents in the DNA direct reversal repair (DRR) pathway. Three single nucleotide polymorphism (SNP) coding for non-conservative amino acid substitutions have been identified [C250T (Leu84Phe), A427G (Ile143Val) and A533G (Lys178Arg)]. To examine the importance of the DRR pathway in risk for breast cancer and the potential interaction with cigarette smoking and dietary antioxidants, we genotyped for these variants using biospecimens from the Long Island Breast Cancer Study Project. Genotyping was performed by a high throughput assay with fluorescence polarization and included 1067 cases and 1110 controls. Overall, there was no main effect between any variant genotype, haplotype or diplotype and breast cancer risk. Heavy smoking (>31 pack-year) significantly increased breast cancer risk for women with the codon 84 variant T-allele [odds ratio, OR = 3.0, 95% confidence interval (95% CI) = 1.4–6.2]. An inverse association between fruits and vegetables consumption and breast cancer risk was observed among women with the wild-type genotype for codon 84 (OR = 0.8, 95% CI = 0.6–0.9 for 
35 servings of fruits and vegetables per week and CC genotype versus those with <35 servings per week and CC genotype). The association between fruits and vegetables consumption and reduced breast cancer risk was apparent among women with at least one variant allele for codon 143 (OR = 0.6, 95% CI = 0.5–0.9 for 35 servings of fruits and vegetables per week and AG or GG genotype versus those with <35 servings per week and AA genotype). Similar patterns were observed for dietary 
-carotene and supplemental ß-carotene, but not for supplemental vitamins C and E. These data suggest that polymorphisms in MGMT may modulate the inverse association previously observed between fruits and vegetables consumption, dietary antioxidants and breast cancer risk, and support the importance of fruits and vegetables on breast cancer risk reduction.
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- MGMT genotype modulates the associations between cigarette smoking, dietary antioxidants and breast cancer risk
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