Maternal cohort study of the Nurses' Health Studies

目的：本研究的目的是检查子宫内和早期生活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于生殖危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期和幼儿期的激素水平高十倍。这些内源性激素水平在妊娠期间可能“编程”终身激素水平。此外，胎儿在子宫内对营养环境的适应可能会“编程”细胞生长，其中较大的新生儿可能有过多的卡路里或个体营养物质，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完全依赖于父母来源的基因表达的细胞表达一个等位基因而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等激素通路中得到了证明。因此，基因组、激素和营养水平的胎儿编程可能影响成人患癌症的风险；另外，生命早期暴露也可能因另一个关键时期的暴露或成年期的饮食摄入等暴露而改变。进展：NCI批准了一项方案，通过回顾性队列设计，与妇女的母亲联系，回忆有关产前、产后和儿童早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，大多数母亲将把婴儿书籍作为验证信息的数据源。产妇数据将与两项正在进行的大规模前瞻性队列研究联系起来，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，她们已报告了关于公认的癌症风险因素的数据，并正在对她们进行随访，以诊断癌症发病率和死亡率。数据收集始于2001年春季向护士女儿发送的第一波邀请函和2001年8月向母亲发送的第一波母亲问卷。截至2001年9月，已有超过25万名母亲返回了调查问卷。

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.