Smoking Research Today is a free monthly online journal that collates and summarizes the latest research about Smoking, including details on cigarettes, cancer, lung, tar, nicotine. | ||||||||
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IGHMBP2 Thr671Ala polymorphism might be a modifier for the effects of cigarette smoking and PAH-DNA adducts to breast cancer risk.Shen J, Beth Terry M, Gammon MD, Gaudet MM, Teitelbaum SL, Eng SM, Sagiv SK, Neugut AI, Santella RM Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA. js2182@columbia.edu Laboratory and bioinformatics studies have suggested that immunoglobulin mu-binding protein 2 (IGHMBP2) is involved in DNA repair, replication and recombination. Using 1067 cases and 1110 controls from a population-based case-control study, we sought to clarify the potential role of the IGHMBP2 Thr671Ala polymorphism (A to G substitution) alone and as a modifier of the effects for cigarette smoking and PAH-DNA adducts on breast cancer risk. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, there was no significant association between the IGHMBP2 variant-G allele and breast cancer risk (OR = 1.1, 95% CI = 0.9-1.3). Increased risk was found among women who had detectable PAH-DNA adducts and carried at least one variant-G allele (OR = 1.4, 95% CI = 1.0-1.8, p for trend = 0.01) compared to women carrying the wild-type AA genotype and with non-detectable adducts. Smokers carrying the IGHMBP2 variant-G allele had no significant increased breast cancer risk compared with non-smoking women with the AA genotype. Heavy smokers (>31 pack years) had a statistically significant association with breast cancer risk (OR=2.0, 95% CI=1.2-3.3) relative to nonsmokers with the AA genotype though the magnitude of association was not different than heavy smokers (> 31 pack years) with the AA genotype (OR=1.6, 95% CI=0.9-2.6). Overall our study observes only modestly higher effect estimates for PAH-DNA adduct exposure and cigarette smoking among those with the high-risk genotype, but these differences are not statistically significant. Additional studies focused on the biological function of the variant-G allele and interactions with other genetic polymorphisms are necessary to confirm our findings. Published 9 August 2006 in Breast Cancer Res Treat, 99(1): 1-7.
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