Sagiv Sharon K, Gaudet Mia M, Eng Sybil M, Abrahamson Page E, Shantakumar Sumitra, Teitelbaum Susan L, Bell Paula, Thomas Joyce A, Neugut Alfred I, Santella Regina M, Gammon Marilie D
Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA.
Environ Res. 2009 Apr;109(3):287-91. doi: 10.1016/j.envres.2008.11.005. Epub 2009 Jan 31.
Polycyclic aromatic hydrocarbons (PAH) are mammary carcinogens in animal studies, and a few epidemiologic studies have suggested a link between elevated levels of PAH-DNA adducts and breast cancer incidence. An association between PAH-DNA adducts and survival among breast cancer cases has not been previously reported. We conducted a survival analysis among women with newly diagnosed invasive breast cancer between 1996 and 1997, enrolled in the Long Island Breast Cancer Study Project. DNA was isolated from blood samples that were obtained from cases shortly after diagnosis and assayed for PAH-DNA adducts using ELISA. Among the 722 cases with PAH-DNA adduct measurements, 97 deaths (13.4%) from all causes and 54 deaths (7.5%) due to breast cancer were reported to the National Death Index (NDI) by December 31, 2002. Using Cox proportional hazards models and controlling for age at diagnosis, we did not find evidence that all-cause mortality (hazard ratio (HR)=0.88; 95% confidence interval (CI): 0.57-1.37), or breast cancer mortality (HR=1.20; 95% CI: 0.63-2.28) was strongly associated with detectable PAH-DNA adduct levels compared with non-detectable adducts; additionally, no dose-response association was observed. Among a subgroup with treatment data (n=520), adducts were associated with over a two-fold higher mortality among those receiving radiation, but mortality for adducts was reduced among hormone therapy users. Results from this large population-based study do not provide strong support for an association between detectable PAH-DNA adducts and survival among women with breast cancer, except perhaps among those receiving radiation treatment.
多环芳烃(PAH)在动物研究中是乳腺致癌物,一些流行病学研究表明,PAH-DNA加合物水平升高与乳腺癌发病率之间存在联系。此前尚未报道PAH-DNA加合物与乳腺癌患者生存率之间的关联。我们对1996年至1997年间新诊断为浸润性乳腺癌的女性进行了生存分析,这些女性参加了长岛乳腺癌研究项目。从诊断后不久采集的病例血样中分离出DNA,并使用酶联免疫吸附测定法检测PAH-DNA加合物。在722例进行了PAH-DNA加合物测量的病例中,截至2002年12月31日,有97例(13.4%)因各种原因死亡,54例(7.5%)因乳腺癌死亡,这些信息已上报至国家死亡指数(NDI)。使用Cox比例风险模型并控制诊断时的年龄,我们没有发现证据表明,与未检测到加合物的情况相比,可检测到的PAH-DNA加合物水平与全因死亡率(风险比(HR)=0.88;95%置信区间(CI):0.57 - 1.37)或乳腺癌死亡率(HR = 1.20;95% CI:0.63 - 2.28)有强烈关联;此外,未观察到剂量反应关联。在有治疗数据的亚组(n = 520)中,加合物与接受放疗者的死亡率高出两倍以上有关,但激素治疗使用者中加合物导致的死亡率有所降低。这项基于大量人群的研究结果并不强烈支持可检测到的PAH-DNA加合物与乳腺癌女性生存率之间存在关联,可能接受放射治疗的患者除外。