Garcia Erika, Hurley Susan, Nelson David O, Hertz Andrew, Reynolds Peggy
Cancer Prevention Institute of California, Berkeley, CA, 94704, USA.
School of Public Health, University of California, Berkeley, CA, 94720, USA.
Environ Health. 2015 Jan 30;14:14. doi: 10.1186/1476-069X-14-14.
Studies suggest that higher breast cancer rates in urban areas persist after accounting for the prevalence of known risk factors, leading to speculation that urban environmental exposures, such as air pollution, may play a role in the etiology of breast cancer. Combining modeled ambient air concentrations with data from a large prospective cohort of California women with over 15 years of follow-up, we examined the relationship between breast cancer incidence and modeled concentrations of air pollutants shown to be mammary gland carcinogens (MGCs).
The study population of 112,378 California Teachers Study participants included 5,676 women diagnosed with invasive breast cancer. Modeled annual average ambient air concentrations of 24 MGCs from the U.S. Environmental Protection Agency were linked to participants' addresses. Cox proportional hazards models were used to estimate hazard rate ratios and 95% confidence intervals associated with residential MGC levels. MGCs were examined individually and as a combined summary variable for all participants, in selected subsets, and by tumor hormone responsiveness.
Initial models yielded some evidence for increased risk for several compounds, including acrylamide, carbon tetrachloride, chloroprene, 4,4'-methylene bis(2-chloroaniline), propylene oxide, and vinyl chloride, but after adjustment for multiple comparisons, only results for propylene oxide and vinyl chloride remained statistically significant. In subset analyses, estrogen-receptor positive or progesterone-receptor positive (ER+/PR+) tumors were associated with higher ambient levels of acrylamide, benzidine, carbon tetrachloride, ethylidene dichloride, and vinyl chloride, while ER-/PR- tumors were associated with higher ambient levels of benzene. Interesting results for different compounds were observed within certain subsets of the population.
While our initial models yielded several elevated risk estimates, after adjusting for multiple comparisons and breast cancer risk factors, most hazard ratios were no longer statistically significant. Our subset analyses, however, suggest that elevated risk may be associated with some compounds for certain subgroups of interest. A summary variable for all 24 MGCs did not offer any advantage over the models for individual compounds. Results must be interpreted cautiously, as estimated exposure was limited to modeled annual average ambient air concentrations, and could not account for other sources or routes other than inhalation.
研究表明，在考虑已知风险因素的患病率后，城市地区较高的乳腺癌发病率依然存在，这引发了一种推测，即城市环境暴露，如空气污染，可能在乳腺癌的病因中起作用。我们将模拟的环境空气浓度与来自加利福尼亚州一个大型前瞻性队列的女性数据相结合，这些女性有超过15年的随访记录，我们研究了乳腺癌发病率与被证明为乳腺致癌物（MGCs）的空气污染物模拟浓度之间的关系。
这项研究的人群包括112378名加利福尼亚教师研究参与者，其中5676名女性被诊断患有浸润性乳腺癌。将美国环境保护局模拟的24种MGCs的年平均环境空气浓度与参与者的地址相关联。使用Cox比例风险模型来估计风险率比以及与居住环境中MGC水平相关的95%置信区间。对MGCs进行单独分析，并作为所有参与者、选定亚组以及按肿瘤激素反应性分类的综合汇总变量进行分析。
初始模型显示出一些证据，表明几种化合物的风险增加，包括丙烯酰胺、四氯化碳、氯丁二烯、4,4'-亚甲基双（2-氯苯胺）、环氧丙烷和氯乙烯，但在进行多重比较调整后，只有环氧丙烷和氯乙烯的结果仍具有统计学意义。在亚组分析中，雌激素受体阳性或孕激素受体阳性（ER+/PR+）肿瘤与丙烯酰胺、联苯胺、四氯化碳、二氯乙烷和氯乙烯的较高环境水平相关，而ER-/PR-肿瘤与苯的较高环境水平相关。在特定人群亚组中观察到了不同化合物的有趣结果。
虽然我们的初始模型产生了几个升高的风险估计值，但在调整多重比较和乳腺癌风险因素后，大多数风险比不再具有统计学意义。然而，我们的亚组分析表明，对于某些感兴趣的亚组，风险升高可能与某些化合物有关。所有24种MGCs的综合汇总变量在个体化合物模型方面没有任何优势。由于估计的暴露仅限于模拟的年平均环境空气浓度，且无法考虑除吸入以外的其他来源或途径，因此结果必须谨慎解释。
