Bone Mineral Density and Subsequent Cancer Risk
Recent cohort studies demonstrated reduced breast cancer risks among women with a history of
fractures or low bone mineral density (BMD). In the Study of Osteoporotic Fractures, each
standard deviation increase in distal radius BMD was associated with a 50% increased risk
over three years of follow-up, while in the Framingham study, women in the highest quartile
of metacarpal bone mass had a 3.5-fold higher risk than women in the lowest quartile. The
impact of the severity and timing of bone loss on risk has not been investigated, and the
extent to which other risk factors (family history, lifestyle, and exogenous hormones)
modify the relationship with BMD is unknown.
To elaborate on these research questions, we conducted a follow-up study of postmenopausal
women who volunteered for the Fracture Intervention Trial (FIT), a trial of the
bone-enhancing drug alendronate. The BFIT follow-up study includes 15,595 of the 22,695 FIT
volunteers. Surviving members of FIT were contacted to ascertain incident cancers and to
provide updated risk factor and fracture history through a self-administered questionnaire.
To supplement baseline serum samples, we used a nested case-control approach to collect
buccal cell specimens for biomarker measurement, including endogenous hormones and genetic
polymorphisms involved in either bone growth (e.g., vitamin D receptor) or hormone
metabolism (e.g., CYPI7, COMT). Operative and pathology reports were used to validate
self-reported cancers. The social security numbers and contact names provided by FIT
participants at baseline facilitated comprehensive follow-up and a National Death Index
search for those who could not be located.
This large cohort includes extensive baseline information on major breast cancer risk
factors, and thus is ideal for evaluating potential interactions with BMD and the effects of
BMD on other cancer sites. Endometrial cancer has been reported to occur more frequently
among women with a history of fracture, but no previous studies have investigated its
relationship to BMD. We are investigating whether proximal femur BMD predicts breast cancer
risk; whether breast cancer risk factors among postmenopausal women modify the relationship
with BMD; whether BMD predicts cancer risk; and whether biomarkers offer etiologic clues
about BMD and cancer risk. Currently, we are examining: 1) the relationship of serum
adipocytokines to endometrial cancer risk, and 2) the relationships of serum estrogens and
metabolites to postmenopausal breast cancer risk. The baseline and follow-up data and the
collection of additional biospecimens should enable us to answer important questions about
BMD and other cancers.
Louise Brinton, Ph.D.
National Cancer Institute (NCI)
United States: Federal Government
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