Steven Stellman - Polymorphisms in DNA Repair Genes, Traffic-Related Polycyclic Aromatic Hydrocarbon Exposure, and Breast Cancer Incidence

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      Mordukhovich, I., Beyea, J., Herring, A. H., Hatch, M., Stellman,   S. D., Teitelbaum, S. L., Richardson, D. B., Millikan, R. C.,   Engel, L. S., Shantakumar, S., Steck, S. E., Neugut, A. I.,   Rossner, P., Jr., Santella, R. M., Gammon, M. D. -

      Abstract: Vehicular traffic polycyclic aromatic   hydrocarbons (PAHs) have been associated with breast cancer   incidence in epidemiologic studies, including our own. Because   PAHs damage DNA by forming adducts and oxidative lesions, genetic   polymorphisms that alter DNA repair capacity may modify   associations between PAH-related exposures and breast cancer   risk. Our goal was to examine the association between vehicular   traffic exposure and breast cancer incidence within strata of a   panel of nine biologically plausible nucleotide excision repair   (NER) and base excision repair (BER) genotypes. Residential   histories of 1,508 cases and 1,556 controls were assessed in the   Long Island Breast Cancer Study Project between 1996 and 1997 and   used to reconstruct residential traffic exposures to   benzo[a]pyrene, as a proxy for traffic-related PAHs. Likelihood   ratio tests from adjusted unconditional logistic regression   models were used to assess multiplicative interactions. A   gene-traffic interaction was evident (p=0.04) for ERCC2 (Lys751);   when comparing the upper and lower tertiles of 1995 traffic   exposure estimates, the odds ratio (95% confidence interval) was   2.09 (1.13, 3.90) among women with homozygous variant alleles.   Corresponding odds ratios for 1960-1990 traffic were also   elevated nearly 2-3-fold for XRCC1(Arg194Trp), XRCC1(Arg399Gln)   and OGG1(Ser326Cys), but formal multiplicative interaction was   not evident. When DNA repair variants for ERCC2, XRCC1, and OGG1   were combined, among women with 4-6 variants, the odds ratios   were 2.32 (1.22, 4.49) for 1995 traffic and 2.96 (1.06, 8.21) for   1960-1990 traffic. Our study is first to report positive   associations between traffic-related PAH exposure and breast   cancer incidence among women with select biologically plausible   DNA repair genotypes. This article is protected by copyright. All   rights reserved.

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