Journal Article

<i>MGMT</i> genotype modulates the associations between cigarette smoking, dietary antioxidants and breast cancer risk

Jing Shen, Mary Beth Terry, Marilie D. Gammon, Mia M. Gaudet, Susan L. Teitelbaum, Sybil M. Eng, Sharon K. Sagiv, Alfred I. Neugut and Regina M. Santella

in Carcinogenesis

Volume 26, issue 12, pages 2131-2137
Published in print December 2005 | ISSN: 0143-3334
Published online July 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi179
MGMT genotype modulates the associations between cigarette smoking, dietary antioxidants and breast cancer risk

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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 α-carotene and supplemental β-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.

Keywords: CI, confidence interval; DRR, direct reversal repair; ICR, interaction contrast ratio; LIBCSP, Long Island Breast Cancer Study Project; MGMT, O6-methylguanine DNA methyl-transferase; OR, odds ratio.

Journal Article.  6027 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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