Polymorphism in the DNA Repair Gene XPD, Polycyclic Aromatic Hydrocarbon-DNA Adducts, Cigarette Smoking, and Breast Cancer Risk

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Abstract
DNA repair is essential to an individual's ability to respond to damage caused by environmental carcinogens. Alterations in DNA repair genes may affect cancer risk by influencing individual susceptibility to environmental exposures. XPD, a gene involved in nucleotide excision repair, may influence individual DNA repair capacity particularly of bulky adducts. Using a population-based breast cancer case-control study that was specifically conducted to examine markers of environmental exposures, such as polycyclic aromatic hydrocarbons (PAH), on Long Island, NY, we examined whether XPD genotype modified the associations among PAH-DNA adducts, cigarette smoking, and breast cancer risk. Specifically, we examined the XPD polymorphism at exon 23, position 751 in 1,053 breast cancer cases and 1,102 population-based controls. The presence of at least one variant allele (Lys/Gln or Gln/Gln) was associated with a 20% increase in risk of breast cancer [odds ratio (OR), 1.21; 95% confidence interval (95% CI), 1.01-1.44]. The increase in risk for homozygosity of the variant allele (Gln/Gln) seemed limited to those with PAH-DNA adduct levels above the median(OR, 1.61; 95% CI, 0.99-2.63 for adducts above the median versus OR, 1.05; 95% CI, 0.64-1.74 for adductsbelow the median), although the multiplicative interaction was not statistically significant. The increasein risk for homozygosity of the variant allele (Gln/Gln) was only seen among current smokers (OR, 1.97; 95% CI, 1.02-3.81 for current smokers versus OR, 0.87; 95% CI, 0.57-1.32 for never smokers); the multiplicative interaction was statistically significant. Overall, this study suggests that those individuals with this polymorphism in the XPD gene may face an increased risk of breast cancer from PAH-DNA adducts and cigarette smoking.