AS297 - Associations of estrogens, estrogen metabolites, and androgens with risks of endometrial and ovarian cancers in a prospective case-cohort study
Investigator Names and Contact Information
Britton Trabert (britton.trabert@hci.utah.edu)
Introduction/Intent
Endogenous estrogens are recognized as causal agents in the etiologies of breast and endometrial cancers, and may also play a role in the pathogenesis of ovarian cancer. Studies of postmenopausal women have consistently shown that elevated circulating estrogens and androgens are associated with increased risk of endometrial cancer. Few studies of circulating sex-steroid hormones and risk of ovarian cancer have been conducted, and these have inconclusive findings due to limitations of experimental design and low case numbers. Metabolism of estrogens and androgens modulates their bioavailability, affinity to receptors and mutagenic potential. In addition, laboratory data indicate that particular metabolites may themselves have unique roles in physiologic and pathologic processes. Roles of hormone metabolism and of particular metabolites in cancer risk have not been studied in epidemiologic studies of endometrial or ovarian cancers, in part because of the need for a sensitive, reliable, and high through-put assay. We are proposing a nested case-control study of endometrial and ovarian cancers to assess the roles of estrogens, estrogen metabolites, and androgens in the etiologies of these cancers. Cases and shared controls will be drawn from the Women's Health Initiative Observational Study (WHIOS) cohort. Analytes will be measured with a recently developed liquid chromatography/ mass spectrometry (LC-MS) assay that can measure 15 estrogens and estrogen metabolites and four androgens with high sensitivity using limited amounts of serum. The proposed research would benefit from unique WHIOS resources including large numbers of cancer cases, prospectively collected serum and baseline data on important cancer risk factors; we expect that resulting data will be an important contribution to understanding the etiologies of endometrial and ovarian cancers, and of hormone-mediated carcinogenesis. Sharing of controls will make efficient use of WHIOS and laboratory resources. This study will provide a comprehensive assessment of estrogen and androgen exposures in the etiologies of endometrial and ovarian cancers, and will also be the largest prospective study of endogenous sex hormones and risk of these gynecologic cancers done to date.
Specific Aims
Primary Aim
- To study associations between circulating estrogens and estrogen metabolites (in conjugated and unconjugated forms) and androgens with risks of endometrial and ovarian cancers in postmenopausal women. Hormones and metabolites will be considered individually and in groups, based on biologic pathways of hormone metabolism.
Secondary aims include:
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To determine whether findings are similar or different in subgroups stratified in tum, by histologic subtypes (ovarian cancer), obesity (endometrial cancer), and follow-up time.
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To assess co-variation between hormone levels and cancer risk factors, such as anthropometric measures, and reproductive and menstrual histories, and to determine whether effects of obesity or reproductive variables on cancer risk are mediated through their effects on hormone profiles.
