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Follow-Up Study of Women in the Fracture Intervention Trial (FIT)

Bone density has emerged as a potentially important predictor of risk for certain cancers that are influenced by hormones, such as breast and endometrial cancers. In 1992, over 25,000 postmenopausal women volunteered for FIT, a clinical trial to determine whether the drug alendronate could reduce the incidence of osteoporosis fractures. The BFIT study is a retrospective cohort study which will use data from FIT to evaluate how bone mineral density of the hip is related to subsequent cancer risk. 

NCI and FIT investigators contacted FIT volunteers to identify incident cancers, and to evaluate whether risk factor information collected in 1992, such as measured bone mineral density, lifestyle factors, and certain growth factors, predicts subsequent cancer risk. Collection of additional risk factor information during this follow-up, including updated lifestyle factors and a buccal cell sample for genetic analyses, is allowing investigators to further explore the complex relationships between bone mass and other risk factors for breast, endometrial, and other cancers. Currently underway are efforts to understand interrelationships between bone mass and endogenous hormones and risk of these cancers.

Serum Estrogen Metabolites and Cancer Risk in the BFIT Study

Although circulating estrogens have been evaluated in prior epidemiological studies of cancer, numerous questions remain with regard to the role of estrogen metabolites in the development of hormone-related cancers. Hormonal and Reproductive Epidemiology Branch (HREB) investigators are currently conducting a case-cohort study to examine circulating estrogens and estrogen metabolites in relation to four specific cancer endpoints within the BFIT study. The BFIT follow-up study includes postmenopausal women (ages 55-80) who volunteered for the Fracture Intervention Trial (FIT) in 1992-1993. Women who were screened for participation in the trial completed a risk factor questionnaire, provided a baseline blood sample and underwent a bone mineral density scan. As part of the BFIT study, these women were followed (median 10.3 years) to ascertain incident cancer outcomes and incident fractures through the period of 2001-2004. A comprehensive profile of endogenous estrogens, including 15 estrogens and estrogen metabolites, is being measured in pre-diagnostic serum the LC-MS2 assay developed at the SAIC-Frederick Hormone Laboratory. These measures will be examined in relation to breast (n~420), endometrial (n~62), ovarian (n~65), and colorectal (n~178) cancers. In addition to the evaluation of a comprehensive estrogen profile, this study is unique in that investigators will also be able to examine the interrelationships with measured bone density. Results from this study will further our understanding of endogenous estrogen exposure, bone mineral density, and cancer risk.

Adipocytokines and Endometrial Cancer Risk in the BFIT Study

Obesity is a well established risk factor for endometrial cancer and may independently affect endometrial cancer risk, even after adjustment for sex steroids. Adipose tissue produces several adipocytokines, including leptin and adiponectin, and although few studies have assessed these markers in relation to endometrial cancer risk, the majority of studies have utilized post-diagnostic blood samples. HREB investigators are currently conducting a nested case-control study to examine circulating pre-diagnostic levels of adiponectin, high molecular weight adiponectin, leptin, and C-peptide in relation to endometrial cancer risk among a subset of postmenopausal women (~60 cases/120 controls) in the BFIT follow-up study. Within this study, investigators will also be able to evaluate a full panel of circulating estrogens and estrogen metabolites as well as investigate relationships with obesity metrics such as body mass index and waist-to-hip ratio. 

For more information, contact Louise Brinton.

Hormonal and Reproductive Epidemiology Branch - Research Areas