Insulin-Like Growth Factor-I and Cancer Mortality in Older Men

Context: Although numerous studies have explored the relation of IGF-I with cancer incidence, few have investigated the association between IGF-I and cancer mortality. Objective: This study examined the association of serum IGF-I levels with cancer mortality in older community-dwelling men. Design, Setting, and Participants: We conducted a prospective, population-based study of 633 men aged 50 yr and older (mean = 73) who attended a 1988-1991 research clinic visit when blood was obtained for measurement of IGF-I. Participants were followed for vital status through July 2006. Main Outcome Measure: All-cancer mortality was assessed. Results: Median IGF-I was 96 ng/ml. During the 18-yr follow-up, 368 deaths occurred; 74 (20%) were due to cancer. Cox regression analyses showed a significant quadratic association between IGF-I and all-cancer mortality (P = 0.039). Higher levels of IGF-I were associated with progressively higher risk of cancer death after adjusting for age, IGF-binding protein-1, adiposity, exercise, current smoking, and previous cancer. The adjusted risk of cancer death was statistically significant for IGF-I levels above 120 ng/ml, with magnitudes of effect ranging from 1.61 [95% confidence interval (CI) = 1.28-2.02] to 2.61 (95% CI = 1.46-4.64). For the 46% of men with IGF-I above 100 ng/ml, the risk of fatal cancer was 1.82 (95% CI = 1.11-2.96) compared to the risk with lower levels. Conclusions: Higher serum IGF-I in older men is associated with increased risk of cancer death, independent of age, adiposity, lifestyle, and cancer history. These results suggest caution in the use of IGF-I-enhancing therapies to slow the adverse effects of aging. (J Clin Endocrinol Metab 95: 1054-1059, 2010)