Maternal cohort study of the Nurses Health Studies

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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.