title: Polymorphisms in DNA repair genes, traffic-related polycyclic aromatic hydrocarbon exposure and breast cancer incidence.
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.
authors.affiliation: Department of Epidemiology, Lambertville, NJ.
authors.forename: Irina
authors.initials: I
authors.lastname: Mordukhovich
authors.affiliation: Consulting in the Public Interest, Lambertville, NJ.
authors.forename: Jan
authors.initials: J
authors.lastname: Beyea
authors.affiliation: Biostatistics, University of North Carolina, Chapel Hill, NC.|Carolina Population Center, University of North Carolina, Chapel Hill, NC.
authors.forename: Amy H
authors.initials: AH
authors.lastname: Herring
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Maureen
authors.initials: M
authors.lastname: Hatch
authors.affiliation: Department of Epidemiology, Columbia University, New York, NY.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Stellman
authors.affiliation: Department of Preventive Medicine, Mount Sinai School of Medicine, New York, NY.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Teitelbaum
authors.affiliation: Department of Epidemiology, Lambertville, NJ.
authors.forename: David B
authors.initials: DB
authors.lastname: Richardson
authors.affiliation: Department of Epidemiology, Lambertville, NJ.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Millikan
authors.affiliation: Department of Epidemiology, Lambertville, NJ.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Engel
authors.affiliation: Glaxo-Smith Kline, Inc, Singapore.
authors.forename: Sumitra
authors.initials: S
authors.lastname: Shantakumar
authors.affiliation: Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, South Carolina, CA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Steck
authors.affiliation: Department of Epidemiology, Columbia University, New York, NY.|Departments of Medicine, Columbia University, New York, NY.
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Neugut
authors.affiliation: Environmental Health Sciences, Columbia University, New York, NY.|Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine as CR, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Rossner
authors.affiliation: Environmental Health Sciences, Columbia University, New York, NY.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.affiliation: Department of Epidemiology, Lambertville, NJ.
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009518:New York / Q000453:epidemiology; D016017:Odds Ratio; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D001335:Vehicle Emissions
chemical_list: D011084:Polycyclic Aromatic Hydrocarbons; D001335:Vehicle Emissions
keywords: DNA repair; breast cancer; polycyclic aromatic hydrocarbons; traffic