Rundle A, Tang D, Hibshoosh H, Estabrook A, Schnabel F, Cao W, Grumet S, Perera F P
Division of Environmental Health Sciences, Joseph L. Mailman School of Public Health, 60 Haven Ave, New York, NY 10032, USA.
Carcinogenesis. 2000 Jul;21(7):1281-9.
A number of polycyclic aromatic hydrocarbons (PAH) are widespread environmental contaminants that cause mammary cancer experimentally. We investigated whether exposure and susceptibility to PAH, as measured by PAH-DNA adducts in breast tissue, are associated with human breast cancer. We carried out a hospital-based case-control study using immunohistochemical methods to analyze PAH-DNA adducts in tumor and nontumor breast tissue from cases and benign breast tissue from controls. The subjects were white, African-American and Latina women without prior cancer or treatment, including 119 women with breast cancer and 108 with benign breast disease without atypia. PAH-DNA adducts measured in breast tumor tissue of 100 cases and in normal tissue from 105 controls were significantly associated with breast cancer (OR=4.43, 96% CI 1.09-18.01) after controlling for known breast cancer risk factors and current active and passive smoking, and dietary PAH. There was substantial interindividual (17-fold) variability in adducts overall, with 27% of cases and 13% of controls having elevated adducts. The odds ratio for elevated adducts in tumor tissue compared with control tissue was 2.56 (1. 05-6.24), after controlling for potential confounders. Adduct levels in tumor tissue did not vary by stage or tumor size. Among 86 cases with paired tumor and nontumor tissue, adducts levels in these two tissues were highly correlated (r=0.56, P<0.001). However, the corresponding associations between case-control status and adducts measured in nontumor tissue from 90 cases and in normal tissue from 105 controls were positive but not statistically significant. Overall, neither active nor passive smoking, or dietary PAH were significantly associated with PAH-DNA adducts or breast cancer case-control status. These results suggest that genetic damage reflecting individual exposure and susceptibility to PAH may play a role in breast cancer; but more research is needed to determine whether the findings are relevant to causation or progression of breast cancer.
多种多环芳烃（PAH）是广泛存在的环境污染物，可在实验中引发乳腺癌。我们调查了通过乳腺组织中PAH - DNA加合物测量的PAH暴露及易感性是否与人类乳腺癌相关。我们开展了一项基于医院的病例对照研究，使用免疫组化方法分析病例的肿瘤和非肿瘤乳腺组织以及对照的良性乳腺组织中的PAH - DNA加合物。研究对象为未患过癌症或接受过治疗的白人、非裔美国人和拉丁裔女性，包括119例乳腺癌患者和108例无异型性的良性乳腺疾病患者。在控制已知的乳腺癌风险因素、当前主动和被动吸烟以及膳食PAH后，100例病例的乳腺肿瘤组织和105例对照的正常组织中测量的PAH - DNA加合物与乳腺癌显著相关（OR = 4.43，96% CI 1.09 - 18.01）。总体而言，加合物存在较大的个体间差异（17倍），27%的病例和13%的对照加合物水平升高。在控制潜在混杂因素后，肿瘤组织中加合物水平升高与对照组织相比的优势比为2.56（1.05 - 6.24）。肿瘤组织中的加合物水平不因分期或肿瘤大小而变化。在86例配对的肿瘤和非肿瘤组织的病例中，这两种组织中的加合物水平高度相关（r = 0.56，P < 0.001）。然而，90例病例的非肿瘤组织和105例对照的正常组织中测量的病例对照状态与加合物之间的相应关联为阳性，但无统计学意义。总体而言，主动或被动吸烟以及膳食PAH均与PAH - DNA加合物或乳腺癌病例对照状态无显著关联。这些结果表明，反映个体对PAH暴露和易感性的基因损伤可能在乳腺癌中起作用；但需要更多研究来确定这些发现是否与乳腺癌的病因或进展相关。
