IGHMBP2Thr671Ala polymorphism might be a modifier for the effects of cigarette smoking and PAH–DNA adducts to breast cancer risk

Laboratory and bioinformatics studies have suggested that immunoglobulin μ-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 IGHMBP2Thr671Ala 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 IGHMBP2variant-Gallele 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-Gallele (OR = 1.4, 95% CI  = 1.0–1.8, pfor trend = 0.01) compared to women carrying the wild-type AAgenotype and with non-detectable adducts. Smokers carrying the IGHMBP2variant-Gallele had no significant increased breast cancer risk compared with non-smoking women with the AAgenotype. 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-Gallele and interactions with other genetic polymorphisms are necessary to confirm our findings.Laboratory and bioinformatics studies have suggested that immunoglobulin μ-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 IGHMBP2Thr671Ala 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 IGHMBP2variant-Gallele 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-Gallele (OR = 1.4, 95% CI  = 1.0–1.8, pfor trend = 0.01) compared to women carrying the wild-type AAgenotype and with non-detectable adducts. Smokers carrying the IGHMBP2variant-Gallele had no significant increased breast cancer risk compared with non-smoking women with the AAgenotype. 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-Gallele and interactions with other genetic polymorphisms are necessary to confirm our findings.