Silent Spring Institute, 320 Nevada Street, Newton, MA 02460, United States.
Environ Res. 2018 Jan;160:152-182. doi: 10.1016/j.envres.2017.08.045. Epub 2017 Oct 6.
Many common environmental chemicals are mammary gland carcinogens in animal studies, activate relevant hormonal pathways, or enhance mammary gland susceptibility to carcinogenesis. Breast cancer's long latency and multifactorial etiology make evaluation of these chemicals in humans challenging.
For chemicals previously identified as mammary gland toxicants, we evaluated epidemiologic studies published since our 2007 review. We assessed whether study designs captured relevant exposures and disease features suggested by toxicological and biological evidence of genotoxicity, endocrine disruption, tumor promotion, or disruption of mammary gland development.
We systematically searched the PubMed database for articles with breast cancer outcomes published in 2006-2016 using terms for 134 environmental chemicals, sources, or biomarkers of exposure. We critically reviewed the articles.
We identified 158 articles. Consistent with experimental evidence, a few key studies suggested higher risk for exposures during breast development to dichlorodiphenyltrichloroethane (DDT), dioxins, perfluorooctane-sulfonamide (PFOSA), and air pollution (risk estimates ranged from 2.14 to 5.0), and for occupational exposure to solvents and other mammary carcinogens, such as gasoline components (risk estimates ranged from 1.42 to 3.31). Notably, one 50-year cohort study captured exposure to DDT during several critical windows for breast development (in utero, adolescence, pregnancy) and when this chemical was still in use. Most other studies did not assess exposure during a biologically relevant window or specify the timing of exposure. Few studies considered genetic variation, but the Long Island Breast Cancer Study Project reported higher breast cancer risk for polycyclic aromatic hydrocarbons (PAHs) in women with certain genetic variations, especially in DNA repair genes.
New studies that targeted toxicologically relevant chemicals and captured biological hypotheses about genetic variants or windows of breast susceptibility added to evidence of links between environmental chemicals and breast cancer. However, many biologically relevant chemicals, including current-use consumer product chemicals, have not been adequately studied in humans. Studies are challenged to reconstruct exposures that occurred decades before diagnosis or access biological samples stored that long. Other problems include measuring rapidly metabolized chemicals and evaluating exposure to mixtures.
许多常见的环境化学物质在动物研究中是乳腺致癌物质，它们激活相关的激素途径，或增强乳腺对致癌作用的易感性。乳腺癌潜伏期长且病因多因素，这使得评估这些化学物质在人类中的作用具有挑战性。
对于先前被确定为乳腺毒性物质的化学物质，我们评估了自 2007 年综述以来发表的流行病学研究。我们评估了研究设计是否捕获了毒理学和生物学证据中提出的相关暴露和疾病特征，这些证据表明这些化学物质具有遗传毒性、内分泌干扰、肿瘤促进或乳腺发育中断。
我们系统地在 PubMed 数据库中搜索了 2006 年至 2016 年期间发表的具有乳腺癌结局的文章，使用了 134 种环境化学物质、来源或暴露生物标志物的术语。我们对文章进行了批判性审查。
我们确定了 158 篇文章。与实验证据一致，少数关键研究表明，在乳腺发育过程中接触滴滴涕（DDT）、二恶英、全氟辛烷磺酸（PFOSA）和空气污染的风险更高（风险估计值范围为 2.14 至 5.0），接触溶剂和其他乳腺致癌物质（如汽油成分）的职业暴露风险更高（风险估计值范围为 1.42 至 3.31）。值得注意的是，一项长达 50 年的队列研究在乳腺发育的几个关键时期（宫内、青春期、妊娠）和 DDT 仍在使用时捕获了 DDT 的暴露情况。大多数其他研究没有评估在生物学相关时期的暴露情况，也没有具体说明暴露的时间。很少有研究考虑遗传变异，但长岛乳腺癌研究项目报告称，具有某些遗传变异的女性多环芳烃（PAHs）的乳腺癌风险更高，尤其是在 DNA 修复基因中。
针对具有毒理学相关性的化学物质并针对遗传变异或乳腺易感性窗口期的生物学假说进行研究的新研究增加了环境化学物质与乳腺癌之间存在联系的证据。然而，许多具有生物学相关性的化学物质，包括目前使用的消费品化学物质，尚未在人类中得到充分研究。这些研究受到挑战，因为它们必须重建几十年前的诊断前暴露情况，或者访问存储了那么长时间的生物样本。其他问题包括测量快速代谢的化学物质和评估暴露于混合物。
