CUNY School of Public Health and Hunter College, New York, New York;
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China; and.
Pediatrics. 2016 Nov;138(Suppl 1):S22-S33. doi: 10.1542/peds.2015-4268E.
Hormone-related cancers have long been thought to be sensitive to exposures during key periods of sexual development, as shown by the vulnerability to such cancers of women exposed to diethylstilbestrol in utero. In addition to evidence from human studies, animal studies using new techniques, such as gene knockout models, suggest that an increasing number of cancers may be hormonally related, including liver, lung, and bladder cancer. Greater understanding of sexual development has also revealed the "mini-puberty" of early infancy as a key period when some sex hormones reach levels similar to those at puberty. Factors driving sex hormones in utero and early infancy have not been systematically identified as potential targets of intervention for cancer prevention. On the basis of sex hormone pathways, we identify common potentially modifiable drivers of sex hormones, including but not limited to factors such as obesity, alcohol, and possibly nitric oxide. We review the evidence for effects of modifiable drivers of sex hormones during the prenatal period and early infancy, including measured hormones as well as proxies, such as the second-to-fourth digit length ratio. We summarize the gaps in the evidence needed to identify new potential targets of early life intervention for lifelong cancer prevention.
激素相关癌症长期以来一直被认为对性发育关键时期的暴露敏感，正如在子宫内暴露于己烯雌酚的女性易患此类癌症所证明的那样。除了来自人类研究的证据外，使用基因敲除模型等新技术的动物研究表明，越来越多的癌症可能与激素有关，包括肝癌、肺癌和膀胱癌。对性发育的进一步了解也揭示了婴儿早期的“迷你青春期”是一个关键时期，在此期间，一些性激素达到与青春期相似的水平。在子宫内和婴儿早期驱动性激素的因素尚未被系统地确定为癌症预防的潜在干预目标。基于性激素途径，我们确定了常见的潜在可改变的性激素驱动因素，包括但不限于肥胖、酒精和可能的一氧化氮等因素。我们回顾了可改变的性激素驱动因素在产前和婴儿早期的影响的证据，包括测量的激素以及代表物，如第二至第四指长度比。我们总结了确定新的潜在目标以进行终生癌症预防的早期生活干预所需的证据差距。
