Mordukhovich Irina, Beyea Jan, Herring Amy H, Hatch Maureen, Stellman Steven D, Teitelbaum Susan L, Richardson David B, Millikan Robert C, Engel Lawrence S, Shantakumar Sumitra, Steck Susan E, Neugut Alfred I, Rossner Pavel, Santella Regina M, Gammon Marilie D
Department of Epidemiology, Lambertville, NJ.
Consulting in the Public Interest, Lambertville, NJ.
Int J Cancer. 2016 Jul 15;139(2):310-21. doi: 10.1002/ijc.30079. Epub 2016 Apr 6.
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.
在包括我们自己的流行病学研究中，车辆交通产生的多环芳烃（PAHs）已被证实与乳腺癌发病率有关。由于PAHs通过形成加合物和氧化损伤来损害DNA，改变DNA修复能力的基因多态性可能会改变PAH相关暴露与乳腺癌风险之间的关联。我们的目标是在一组9种具有生物学合理性的核苷酸切除修复（NER）和碱基切除修复（BER）基因型的分层中，研究车辆交通暴露与乳腺癌发病率之间的关联。在1996年至1997年的长岛乳腺癌研究项目中，评估了1508例病例和1556例对照的居住史，并用于重建居住交通对苯并[a]芘的暴露情况，以此作为与交通相关的PAHs的替代指标。使用调整后的无条件逻辑回归模型的似然比检验来评估相乘交互作用。ERCC2（Lys751）基因与交通的交互作用明显（p = 0.04）；在比较1995年交通暴露估计值的上三分位数和下三分位数时，纯合变异等位基因女性的优势比（95%置信区间）为2.09（1.13，3.90）。对于XRCC1（Arg194Trp）、XRCC1（Arg399Gln）和OGG1（Ser326Cys），1960 - 1990年交通的相应优势比也升高了近2 - 3倍，但正式的相乘交互作用并不明显。当将ERCC2、XRCC1和OGG1的DNA修复变异组合在一起时，在有4 - 6个变异的女性中，1995年交通的优势比为2.32（1.22，4.49），1960 - 1990年交通的优势比为2.96（1.06，8.21）。我们的研究首次报告了在具有特定生物学合理性的DNA修复基因型的女性中，与交通相关的PAH暴露与乳腺癌发病率之间存在正相关。
