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Serum Sex Steroids and Their Metabolites in Relation to Ovarian and Endometrial Cancer

Women’s Health Initiative Observational Study Cohort

In collaboration with investigators from the Women’s Health Initiative, investigators in DCEG are conducting 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 have been drawn from the Women’s Health Initiative Observational Study (WHIOS) cohort. This effort benefits from unique WHIOS resources, including large numbers of cancer cases, prospectively collected serum and baseline data on important cancer risk factors.

A comprehensive profile of endogenous estrogens, including 15 estrogens and estrogen metabolites, were measured in pre-diagnostic serum using the LC-MS/MS assay developed at the Protein Characterization Laboratory at the Frederick National Cancer Center. These measures were examined in relation to ovarian (n~169) and endometrial (n~313) cancers. For ovarian cancer, we found striking heterogeneity in risks by histologic subtype with results supporting a role for estrogen metabolites in the etiology of non-serous, but not serous ovarian cancers. Elevated circulating levels of both parent estrogens and estrogen metabolites were associated with increased endometrial cancer risk, suggesting that estrogen receptor-mediated mechanisms explain a portion of the effects of obesity on endometrial cancer risk. Within this study, investigators have also evaluated the full panel of circulating estrogens and estrogen metabolites to investigate relationships with cancer risk factors (e.g., body mass index, sedentary behavior, alcohol use). Currently underway are efforts to evaluate associations of 11 androgens and androgen metabolites as measured by LC-MS/MS to ovarian and endometrial cancer risks as well as cancer risk factors.

View publications from the WHI-OS nested case-control study.

For more information, contact Christian Abnet

Metabolic Epidemiology Branch - Research Areas