Abstract
BACKGROUND: Predictors of premature death and cancer development are needed to more precisely identify individuals who may warrant preventive intervention. Circulating insulin-like growth factor (IGF)-binding protein-7 (IGFBP7) and, to a lesser extent, the IGFBP7/IGF-1 ratio are emerging biomarkers of renal and cardiovascular morbidity. However, their relationships with aging, obesity, mortality, and cancer risk remain unclear. METHODS: This hypothesis-generating study investigated plasma IGFBP7, IGF-1, and their ratio as predictors of all-cause mortality and the incidence of any cancer (excluding nonmelanoma skin cancer), obesity-related cancer (composite of 13 cancer types), and breast cancer in a large longitudinal cohort of postmenopausal women. We assessed the relationships of each biomarker with age, body mass index, and each outcome (bivariately and controlling for age, body mass index, race, physical activity, education, income, marital status, alcohol intake, smoking, diabetes, and hormone therapy) in 793 Women's Health Initiative Observational Study participants (mean, 19.4-year follow-up). RESULTS: In adjusted analyses, IGFBP7 increased with age and obesity and was positively associated with risks of all-cause mortality [HR = 2.42 (95% confidence interval, 1.37-4.26); P = 0.002], any cancer [HR = 2.04 (1.05-3.94); P = 0.035], and obesity-related cancer [HR = 1.58 (0.99-2.51); P = 0.053]. Also in adjusted analyses, the IGFBP7/IGF-1 ratio increased with age and was positively associated with all-cause mortality [HR = 1.51 (1.14-1.99); P = 0.004] and any cancer incidence [HR = 5.44 (1.13-26.1); P = 0.034]. CONCLUSIONS: Plasma IGFBP7 and the IGFBP7/IGF-1 ratio are positively associated with age, obesity (IGFBP7 only), mortality, and cancer in postmenopausal women. IMPACT: Plasma IGFBP7 may represent an age- and obesity-sensitive biomarker of increased risk of developing cancer and/or dying prematurely.