Maternal cohort study of the Nurses Health Studies

目的：本研究的目的是检查子宫内和生命早期暴露与女性成人癌症风险的关系。背景：流行病学研究主要集中在生殖风险因素作为成人激素状态的指标。最近的研究转向了胎儿环境中的激素和其他暴露，因为胎儿乳腺中的激素水平表明，子宫内的激素暴露比婴儿和幼儿期高出十倍。这些内源性激素水平在怀孕期间可能会“程序”终身水平的激素。此外，胎儿适应其子宫内的营养环境可能会“编程”细胞生长，其中大的新生儿可能已经有过量的卡路里或个别营养素，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具有完全的来源依赖性基因表达的细胞表达一个等位基因，但不表达另一个等位基因，如在胎儿生长和激素途径如胰岛素生长因子II中所证明的。因此，胎儿在基因组、激素和营养水平上的编程可能会影响成年人患癌症的风险;或者，生命早期的暴露可能会因另一个关键时期的暴露或成年后的暴露（如饮食摄入）而改变。进展：NCI已经批准了一项方案，通过一项回顾性队列设计，联系妇女的母亲，回忆有关产前、产后和幼儿期暴露和事件的信息。已经完成了几项试点研究，其中一项研究确定，大多数母亲将婴儿书籍作为验证信息的数据来源。产妇数据将与两项正在进行的大规模前瞻性队列研究（称为护士健康研究I和II）相关联，其中包括128，700名护士，他们报告了有关公认的癌症风险因素的数据，并正在接受癌症发病率和死亡率的诊断。数据收集始于春季向护士女儿发出的第一波邀请信和2001年8月向母亲发出的第一波母亲问题单。截至2001年9月，超过25 000名母亲交回了问卷。

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 genommic 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 crticial 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. Several pilot studies have been completed including one that identified the majority of mothers will have baby books as a data source to validate information. 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. Data collection began with the first wave of invitational letters to the nurse daughter's in the spring and the first wave of maternal questionnaires sent to mothers in August 2001. As of September, 2001, over 25,0000 mothers have returned questionnaires.