Maternal Cohort Study of the Nurses' Health Study

目的：本研究的目的是研究宫内和早期生命暴露与女性成年癌症风险的关系。背景：流行病学研究主要集中在生殖危险因素作为成人荷尔蒙状况的指标。最近，研究转向了胎儿环境中的荷尔蒙和其他暴露，因为胎儿乳腺中的激素水平表明，在子宫中暴露于激素的水平比婴儿和儿童早期的水平高出十倍。怀孕期间的这些内源性激素水平可能会决定一生的荷尔蒙水平。此外，胎儿对其子宫内营养环境的适应可能会导致细胞生长，其中较大的新生儿可能有过多的卡路里或个别营养物质，这可能会提高激素水平或增加细胞大小或数量。最后，基因组印记可以导致基因表达完全依赖于父母的细胞表达一个等位基因，但不表达另一个等位基因，这在胎儿生长和胰岛素生长因子II等激素途径中得到了证明。因此，在基因组、激素和营养水平上的胎儿编程可能会影响成人患癌症的风险；或者，早期生命暴露可能会被另一个关键时期的暴露或成年后饮食摄入等暴露所改变。进展：NCI批准了一项协议，用于联系妇女的母亲，以回顾队列设计中有关产前、产后和儿童早期暴露和事件的信息。产妇数据将与两项正在进行的大型前瞻性队列研究相联系，这两项研究被称为护士健康研究I和II，其中包括128,700名护士，她们报告了公认的癌症风险因素的数据，并正在接受跟踪，以诊断癌症的发生和死亡率。目前正在试行问卷调查，数据收集工作将于2000年秋季开始。

OBJECTIVE: The objective of this study is to examine the relation of in utero and early life exposures on risk of adult cancers in women. BACKGROUND: Epidemiological studies have primarily focused on reproductive risk factors as indicators of adult hormonal status. More recently research has turned to hormonal and other exposures in the fetal environment because exposures to hormones in utero as illustrated by hormone levels in the fetal mammary gland are ten-fold higher than levels in infancy and early childhood. These endogenous hormone levels during gestation may program life-long levels of hormones. Also fetal adaptation to its nutritional environment in utero may program cell growth wherein the large neonate may have had an excess of calories or individual nutrients that may raise hormone levels or increase cell size or number. Finally genomic imprinting can cause cells with a full parent-of-origin-dependent gene expression to express one allele but not the other, as evidenced in fetal growth and in hormonal pathways such as that of insulin-growth factor II. Thus fetal programming at the genomic, hormonal and nutritional levels could influence adult risk of cancer; alternatively early life exposures may be modified by exposures at another critical period or by an exposure such as dietary intake in adult years. PROGRESS: A protocol has been approved at NCI to contact mothers of women to recall information about prenatal, postnatal, and early childhood exposures and events in a retrospective cohort design. Maternal data will be linked to two ongoing, large-scale prospective cohort studies, known as the Nurses' Health Studies I and II, including 128,700 nurses who have reported data on recognized risk factors for cancer and who are being followed for diagnosis of incident cancers as well as mortality. The questionniare is being piloted and data collection will begin in the fall of 2000.