Gibson Douglas A, Saunders Philippa T K
Queen's Medical Research Institute, MRC Centre for Reproductive Health, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Endocr Relat Cancer. 2014 Mar 12;21(2):T13-31. doi: 10.1530/ERC-13-0342. Print 2014 Apr.
Endocrine disrupting chemicals (EDC) are ubiquitous and persistent compounds that have the capacity to interfere with normal endocrine homoeostasis. The female reproductive tract is exquisitely sensitive to the action of sex steroids, and oestrogens play a key role in normal reproductive function. Malignancies of the female reproductive tract are the fourth most common cancer in women, with endometrial cancer accounting for most cases. Established risk factors for development of endometrial cancer include high BMI and exposure to oestrogens or synthetic compounds such as tamoxifen. Studies on cell and animal models have provided evidence that many EDC can bind oestrogen receptors and highlighted early life exposure as a window of risk for adverse lifelong effects on the reproductive system. The most robust evidence for a link between early life exposure to EDC and adverse reproductive health has come from studies on women who were exposed in utero to diethylstilbestrol. Demonstration that EDC can alter expression of members of the HOX gene cluster highlights one pathway that might be vulnerable to their actions. In summary, evidence for a direct link between EDC exposure and cancers of the reproductive system is currently incomplete. It will be challenging to attribute causality to any single EDC when exposure and development of malignancy may be separated by many years and influenced by lifestyle factors such as diet (a source of phytoestrogens) and adiposity. This review considers some of the evidence collected to date.
内分泌干扰化学物质（EDC）是普遍存在且持久的化合物，有能力干扰正常的内分泌稳态。女性生殖道对性类固醇的作用极为敏感，雌激素在正常生殖功能中起关键作用。女性生殖道恶性肿瘤是女性中第四大常见癌症，其中子宫内膜癌占大多数病例。子宫内膜癌发生的既定风险因素包括高体重指数以及接触雌激素或他莫昔芬等合成化合物。对细胞和动物模型的研究已提供证据表明，许多EDC可与雌激素受体结合，并强调生命早期暴露是对生殖系统产生不良终身影响的风险窗口。生命早期暴露于EDC与不良生殖健康之间存在关联的最有力证据来自对子宫内接触己烯雌酚的女性的研究。证明EDC可改变HOX基因簇成员的表达突出了一条可能易受其作用影响的途径。总之，目前EDC暴露与生殖系统癌症之间存在直接关联的证据尚不完整。当暴露与恶性肿瘤的发生可能相隔多年且受饮食（植物雌激素的一个来源）和肥胖等生活方式因素影响时，将因果关系归因于任何单一的EDC都将具有挑战性。本综述考虑了迄今为止收集到的一些证据。
