Both Low and High Serum IGF-I Levels Associate with Cancer Mortality in Older Men

Background: Although recent population-based studies suggest a U-shaped relationship between serum IGF-I concentration and all-cause mortality, the distribution of death causes underlying this association remains unclear. We hypothesized that high IGF-I levels associate with increased cancer mortality, whereas low IGF-I levels associate with increased cardiovascular disease (CVD) mortality. Methods: Serum IGF-I levels were measured in 2901 elderly men (mean age 75.4, range 69-81 yr) included in the prospective population-based Osteoporotic Fractures in Men Study (Sweden) study. Mortality data were obtained from central registers with no loss of follow-up. The statistical analyses included Cox proportional hazards regressions with or without a spline approach. Results: During the follow-up (mean 6.0 yr), 586 of the participants died (cancer deaths, n = 211; CVD deaths, n = 214). As expected, our data revealed a U-shaped association between serum IGF-I levels and all-cause mortality. Low as well as high serum IGF-I (quintile 1 or 5 vs. quintiles 2-4) associated with increased cancer mortality [hazard ratio (HR) = 1.86, 95% confidence interval (CI) = 1.34-2.58; and HR = 1.90, 95% CI = 1.37-2.65, respectively]. Only low serum IGF-I associated with increased CVD mortality (quintile 1 vs. quintiles 2-4, HR = 1.48,95% CI = 1.08-2.04). These associations remained after adjustment for multiple covariates and exclusion of men who died during the first 2 yr of follow-up. Conclusions: Our findings demonstrate that both low and high serum IGF-I levels are risk markers for increased cancer mortality in older men. Moreover, low IGF-I levels associate with increased CVD mortality. (J Clin Endocrinol Metab 97: 4623-4630, 2012)