A Western lifestyle, including type of diet, lack of physical activity, and certain childbearing patterns, is associated with high risks of cancers of the breast, endometrium, and ovary. A widely held view is that effects of lifestyle factors on cancer risk are mediated through alterations in hormone metabolism. One feature potentially shared by all three forms of cancer is ovarian overproduction of androgens. A second common feature may be elevated plasma and tissue levels of insulin or insulin-like growth factor-I (IGF-I), or decreased IGF-binding proteins. Insulin is a key hormone in the regulation of energy metabolism and, together with insulin-like growth factor-I, is also central in the regulation of anabolic (growth) processes as function of available energy and elementary substrates (e.g., amino acids). Increased levels of IGF-I, or decreased levels of IGF-binding proteins (IGFBPs), have been shown to promote tumor development by inhibiting apoptosis, and by stimulating cell proliferatton. In addition, insulin and IGF-I enhance ovarian androgen production and down regulate hepatic production and plasma levels of SHBG. The specific aim of the present proposal is to address the hypothesis that increased (prediagnostic) plasma levels of insulin; and/or increased plasma IGF-I for given concentrations of major IGFBPs (IGFBP-1, -2, -3) are associated with increased risk of ovarian and endometrial cancers and of breast cancer in young women. Through insulin and IGF-I, the study seeks to establish a linkage between exposure to Western lifestyle and over nutrition and imbalances in steroid hormones that are thought to be associated with the three cancers most frequently affecting women. This study is a component (Component 3) of a group of three concurrent studies which address complementary aspects of the role of endogenous hormones in the etiology of ovarian and endometrial cancers, and of breast cancer in young women. All studies are based on the same underlying population, obtained by combining three prospective cohort studies that are currently ongoing in New York, Umea (Sweden) and Milan (Italy).
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