Lichtiger Lydia, Rivera Janelle, Sahay Debashish, Miller Rachel L
Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine, Mount Sinai, New York City, NY, United States.
J Cancer Immunol (Wilmington). 2021;3(3):154-162.
Breast cancer risk remains incompletely explained, and higher incidence rates of breast cancer over recent times and in urban and industrialized areas suggest environmental causes. Polycyclic aromatic hydrocarbons (PAH) are ubiquitous in the environment and epidemiological and rodent studies have shown associations between exposure to PAH and breast cancer incidence as well as mammary tumorigenesis. In addition, and rodent studies have implicated alterations in estrogen receptor alpha () signaling pathways following PAH exposure in limited experimental studies. However, our understanding of these mechanisms is incomplete. Sahay et al. addressed this gap by examining the effect of PAH exposure on epigenetic and transcriptional regulation of genes in the pathway in a mouse cohort exposed to aerosolized PAH at proportions measured in urban air. In addition to alterations in the signaling pathway in the pregnant mice and in their offspring and grandoffspring, the investigators observed higher body weights in mice exposed to PAH compared to the control. Given that associations between mammary tissue adiposity, systemic adiposity, and breast cancer risk have been observed previously, the finding of higher body weight in the PAH exposure group raises the possibility that body weight might influence the association between PAH exposure and breast cancer risk. Along with new analyses, we discuss the possibility that body weight may modify the association between PAH exposure, mammary cellular proliferation, and mammary gland ductal hyperplasia in offspring and grandoffspring mice and future research that may be needed to delineate these associations.
乳腺癌风险仍未得到充分解释，近期以及城市和工业化地区较高的乳腺癌发病率表明存在环境因素。多环芳烃（PAH）在环境中普遍存在，流行病学和啮齿动物研究已表明PAH暴露与乳腺癌发病率以及乳腺肿瘤发生之间存在关联。此外，在有限的实验研究中，啮齿动物研究表明PAH暴露后雌激素受体α（）信号通路会发生改变。然而，我们对这些机制的理解并不完整。萨海等人通过在一个小鼠队列中研究PAH暴露对该信号通路中基因的表观遗传和转录调控的影响来填补这一空白，该队列小鼠暴露于雾化PAH，其比例为城市空气中所测比例。除了怀孕小鼠及其后代和孙代的信号通路发生改变外，研究人员还观察到，与对照组相比，暴露于PAH的小鼠体重更高。鉴于此前已观察到乳腺组织肥胖、全身性肥胖与乳腺癌风险之间存在关联，PAH暴露组体重增加这一发现增加了体重可能影响PAH暴露与乳腺癌风险之间关联的可能性。连同新的分析，我们讨论了体重可能改变后代和孙代小鼠中PAH暴露、乳腺细胞增殖和乳腺导管增生之间关联的可能性，以及可能需要开展哪些未来研究来阐明这些关联。
