BACKGROUND The evidence evaluating environmental chemical exposures (ECE) and breast cancer (BC) risk is heterogeneous which may stem in part as few studies measure ECE during key BC windows of susceptibility (WOS). Another possibility may be that most BC studies are skewed towards individuals at average risk, which may limit the ability to detect signals from ECE. OBJECTIVES We reviewed the literature on ECE and BC focusing on three types of studies or subgroup analyses based on higher absolute BC risk: BC family history (Type 1); early onset BC (Type 2); and/or genetic susceptibility (Type 3). METHODS We systematically searched the PubMed database to identify epidemiologic studies examining ECE and BC risk published through June 1, 2019. RESULTS We identified 100 publications in 56 unique epidemiologic studies. Of these 56 studies, only 2 (3.6%) were enriched with BC family history and only 11% of studies (6/56) were specifically enriched with early onset cases. 80% of the publications from these 8 enriched studies (Type 1: 8/10 publications; Type 2: 8/10 publications) supported a statistically significant association between ECE and BC risk including studies of PAH, indoor cooking, NO2, DDT; PCBs, PFOSA; metals; personal care products; and occupational exposure to industrial dyes. 74% of Type 3 publications (20/27) supported statistically significant associations for PAHs, traffic-related air pollution, PCBs, phthalates, and PFOSAs in subgroups of women with greater genetic susceptibility due to variants in carcinogen metabolism, DNA repair, oxidative stress, cellular apoptosis and tumor suppressor genes. DISCUSSION Studies enriched for women at higher BC risk through family history, younger age of onset and/or genetic susceptibility consistently support an association between an ECE and BC risk. In addition to measuring exposures during WOS, designing studies that are enriched with women at higher absolute risk are necessary to robustly measure the role of ECE on BC risk.

中文翻译：

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潜在易感性背景下的环境暴露和乳腺癌风险：流行病学文献的系统评价。

背景评估环境化学暴露 (ECE) 和乳腺癌 (BC) 风险的证据是异质的，这可能部分是因为很少有研究在关键的 BC 易感性窗口 (WOS) 期间测量 ECE。另一种可能性可能是大多数 BC 研究偏向于处于平均风险的个体，这可能会限制检测 ECE 信号的能力。目标 我们回顾了关于 ECE 和 BC 的文献，重点关注基于更高绝对 BC 风险的三种类型的研究或亚组分析：BC 家族史（1 型）；早发性 BC（2 型）；和/或遗传易感性（类型 3）。方法 我们系统地搜索了 PubMed 数据库，以确定截至 2019 年 6 月 1 日发表的检查 ECE 和 BC 风险的流行病学研究。结果我们在 56 项独特的流行病学研究中确定了 100 篇出版物。在这 56 项研究中，只有 2 项（3. 6%) 丰富了 BC 家族史，只有 11% 的研究 (6/56) 特别丰富了早发病例。这 8 项丰富研究的 80% 的出版物（第 1 类：8/10 出版物；第 2 类：8/10 出版物）支持 ECE 和 BC 风险之间的统计学显着关联，包括对 PAH、室内烹饪、NO2、DDT 的研究；多氯联苯、全氟辛烷磺酸；金属；个人护理产品；和工业染料的职业暴露。74% 的第 3 类出版物 (20/27) 支持多环芳烃、交通相关空气污染、多氯联苯、邻苯二甲酸盐和全氟辛烷磺酸在由于致癌物质代谢、DNA 修复、氧化应激变异而具有更大遗传易感性的女性亚组中具有统计学意义的关联，细胞凋亡和肿瘤抑制基因。讨论 通过家族史丰富了 BC 风险较高的女性的研究，发病年龄和/或遗传易感性始终支持 ECE 和 BC 风险之间的关联。除了测量 WOS 期间的暴露外，还需要设计富含绝对风险较高的女性的研究，以有力地衡量 ECE 对 BC 风险的作用。