Vehicular traffic exposure to polycyclic aromatic hydrocarbons and breast cancer risk Public Deposited

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  • March 22, 2019
Creator
  • Mordukhovich, Irina
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants, known human lung carcinogens, and potent mammary carcinogens in animal models. However, the association between PAHs and breast cancer in women is unclear. Vehicular traffic is a major source of ambient PAH exposure. This study evaluates the association between residential exposure to vehicular traffic-related PAHs and risk of breast cancer, overall and by tumor subtype, and within strata of nucleotide excision repair and base excision repair genotypes and fruit/vegetable intake. For this population-based study, residential histories, dietary intake, and other factors were assessed in 1996-1997 for 1,508 newly diagnosed breast cancer cases and 1,556 controls. Residential traffic exposure estimates were reconstructed using a validated model for the years 1960 through 1995. The following single nucleotide polymorphisms were genotyped: ERCC1 8092C/A, OGG1 Ser326Cys, XPA -4A/G, XPD Lys751Gln and Asp312Asn, XPF Arg415Gln, XPG Asp1104His, XRCC1 Arg194Trp and Arg399Gln. Medical records and archived tumor tissue were used to determine case tumor subtype. In spline figures, which were used to inform quantile cutpoints for regression models, breast cancer risk was increased among women with the top 1% of traffic PAH exposures. Odds ratios (and 95% confidence intervals) for breast cancer, estimated using unconditional logistic regression, were modestly elevated for the top 5% of long-term 1960-1990 traffic PAH exposure estimates, compared with below the median (1.44 (0.78, 2.68)). Associations between recent traffic exposure in 1995 (top 5% vs. below the median) and breast cancer were attenuated toward the null (1.14 (0.80, 1.64)), but were stronger among women with low fruit/vegetable intake (1.46 (0.89, 2.40)) and hormone-receptor negative tumors (1.67 (0.91, 3.05)). Associations were approximately two- to three-fold stronger among women with variant alleles for XPD (Lys751Gln) and XRCC1 (Arg194Trp), and wild-type alleles for XRCC1 (Arg399Gln) and OGG1 (Ser326Cys), when comparing the upper and lower tertiles of traffic exposure during 1995 or 1960-1990. This study reports positive associations between traffic-related PAH exposure and breast cancer risk among women with comparatively high long-term traffic exposures or among those with certain DNA repair genotypes, low fruit/vegetable intake or hormone receptor negative tumors, although confidence intervals were wide.
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  • In Copyright
Advisor
  • Gammon, Marilie D.
Degree
  • Doctor of Philosophy
Graduation year
  • 2013
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