Context: Although numerous studies have explored the relation of insulin-like growth factor-I (IGF-I) with cancer incidence, few have investigated the association between IGF-I and cancer mortality. A meta-analysis suggests that higher serum IGF-I is associated with increased risk of several common cancers including breast, colorectal, and prostate. Objective: To determine the association of serum IGF-I levels with all-cancer mortality in older community-dwelling men. Methods: A prospective population-based study of 633 men aged 50 and older (median 73) who had serum IGF-I measured in 1988-91 and were followed for vital status through July 2006. Results: The median IGF-I level was 96 ng/mL. During the 18-year follow-up, 74 (20%) cancer deaths occurred. Age-adjusted Cox regression analyses showed a significant quadratic relationship between IGF-I levels and all-cancer mortality (p<.05). Increasing IGF-I levels were associated with progressively higher hazards of cancer death adjusting for age, IGF binding protein-1, adiposity, alcohol consumption, current smoking and physical activity (see Table). The adjusted risk of cancer death was 2.61 (95% CI 1.46, 4.64) for men with the highest IGF-I levels (200-239 ng/mL) and 1.82 (95% CI 1.11, 2.96) for the 46% of men with IGF-I above 100 ng/mL compared to those with lower levels. These associations were independent of prevalent cancer at baseline. Exclusion of deaths that occurred during the first 2 years (to minimize the effect of occult disease) yielded similar results. Conclusions: Higher serum IGF-I in older men is associated with increased risk of cancer death, independent of age, adiposity and lifestyle. This association does not appear to be due to pre-existing disease. If confirmed, these results suggest that use of IGF-I enhancing therapies to treat diabetes or slow the adverse effects of aging should be questioned.

99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA