Troisi Rebecca, Potischman Nancy, Hoover Robert N
Room 854, Dartmouth-Hitchcock Medical Center, 7297 Rubin Building, One Medical Center Drive, Lebanon, NH 03756, USA.
Cancer Epidemiol Biomarkers Prev. 2007 Sep;16(9):1700-12. doi: 10.1158/1055-9965.EPI-07-0073.
Prenatal factors have been hypothesized to influence subsequent breast cancer development. Directly evaluating the associations of in utero exposures with risk, however, presents several methodologic and theoretical challenges, including the long induction period between exposure and disease and the lack of certainty regarding the critical timing of exposure. Indirect evaluation of these associations has been achieved by use of proxies such as gestational and neonatal characteristics. Evidence suggests that preeclampsia is associated with a reduced breast cancer risk, whereas high birth weight and dizygotic twinning seem associated with an increased risk. Asians born in Asia have substantially lower breast cancer risks than women born in the West. Although data thus far are few, what exists is not consistent with a unifying hypothesis for a particular biological exposure (such as estrogens or androgens) during pregnancy as mediating the observed associations between pregnancy factors and breast cancer risk. This suggests that additional studies of prenatal factors should seek to broaden the range of hormones, growth, and other endocrine factors that are evaluated in utero. Once candidate biomarkers are identified, assessing them with respect to breast cancer and with intermediate end points in carcinogenesis should be a priority. In addition, investigations should explore the possibility that in utero exposures may not act directly on the breast, but may alter other physiologic pathways such as hormone metabolism that have their effect on risk later in life.
据推测，产前因素会影响后续乳腺癌的发展。然而，直接评估子宫内暴露与风险之间的关联存在一些方法学和理论上的挑战，包括暴露与疾病之间的长诱导期以及暴露关键时间的不确定性。通过使用诸如妊娠和新生儿特征等代理指标对这些关联进行了间接评估。有证据表明，先兆子痫与乳腺癌风险降低有关，而高出生体重和双卵双胎似乎与风险增加有关。在亚洲出生的亚洲人患乳腺癌的风险明显低于在西方出生的女性。尽管目前的数据很少，但现有数据并不支持关于孕期特定生物暴露（如雌激素或雄激素）作为介导妊娠因素与乳腺癌风险之间观察到的关联的统一假设。这表明，对产前因素的进一步研究应寻求扩大子宫内评估的激素、生长和其他内分泌因素的范围。一旦确定了候选生物标志物，优先事项应是评估它们与乳腺癌以及致癌过程中间终点的关系。此外，研究应探讨子宫内暴露可能不会直接作用于乳腺，但可能改变其他生理途径（如激素代谢）从而在生命后期影响风险的可能性。
