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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

  • Epidemiology
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Summary

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 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.

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Acknowledgements

For their valuable contributions to the LIBCSP, the authors thank members of the Long Island Breast Cancer Network; the 31 participating institutions on Long Island and in New York City, NY; our National Institutes of Health collaborators, Gwen Colman, PhD, National Institutes of Environmental Health Sciences; G. Iris Obrams, MD, PhD formerly of the National Cancer Institute; members of the External Advisory Committee to the population-based case-control study: Leslie Bernstein, PhD, (Committee chair); Gerald Akland, MS; Barbara Balaban, MSW; Blake Cady, MD; Dale Sandler, PhD; Roy Shore, PhD; and Gerald Wogan, PhD; as well as other collaborators who assisted with various aspects of our data collection efforts including Gail Garbowski, MPH, Julie Britton, PhD, Mary S. Wolff, PhD, Steve Stellman, PhD, Maureen Hatch, PhD, Geoff Kabat PhD, Bruce Levin, PhD H. Leon Bradlow, PhD; David Camann, BS; Martin Trent, BS; Ruby Senie, PhD; Carla Maffeo, PhD; Pat Montalvan; Gertrud Berkowitz, PhD; Margaret Kemeny, MD; Mark Citron, MD; Freya Schnabel, MD; Allen Schuss, MD; Steven Hajdu, MD; and Vincent Vinceguerra, MD. PAH–DNA adducts (detected by Lianwen Wang, Qiao Wang) and genotyping were completed in Dr Santella’s lab. Funded in part by grants U01 CA/ES66572, P30ES09089, P30ES10126, and K07CA90685-02 from the National Cancer Institute and the National Institute of Environmental Health Sciences, an award from the Breast Cancer Research Foundation and gifts from private citizens.

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Authors and Affiliations

  1. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA

    Jing Shen & Regina M. Santella

  2. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA

    Mary Beth Terry, Sybil M. Eng & Alfred I. Neugut

  3. Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA

    Marilie D. Gammon, Mia M. Gaudet & Sharon K. Sagiv

  4. Department of Community and Preventive Medicine, Mt. Sinai School of Medicine, New York, NY, USA

    Susan L. Teitelbaum

  5. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA

    Jing Shen

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  1. Jing Shen
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Correspondence to Jing Shen.

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Shen, J., Beth Terry, M., Gammon, M.D. et al. IGHMBP2 Thr671Ala polymorphism might be a modifier for the effects of cigarette smoking and PAH–DNA adducts to breast cancer risk. Breast Cancer Res Treat 99, 1–7 (2006). https://doi.org/10.1007/s10549-006-9174-3

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