Plasma Levels of Insulin-Like Growth Factor-1 and Binding Protein-3, and Their Association With Bladder Cancer Risk

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Abstract
Because insulin-like growth factors (IGFs) and their binding proteins have been implicated in the development of prostate, breast, colon and lung cancer, we examined the role of IGF-1 and IGF binding protein-3 levels in bladder cancer risk. We used an enzyme-linked immunosorbent assay to compare plasma levels of IGF-1 and IGF binding protein-3 in 154 patients with bladder cancer and 154 controls from an ongoing case-control study. Mean IGF-1 was significantly higher in cases than in controls (175.8 versus 153.2 ng./ml., p <0.01). Mean IGF binding protein-3 was significantly lower in cases than in controls (2,632.9 versus 3,056.6 ng./ml., p <0.01). The highest quartile plasma levels of IGF-1 were associated with an increased risk of bladder cancer (OR 3.10, 95% CI 1.43 to 6.70) and the highest quartile plasma levels of IGF binding protein-3 were associated with a reduced risk of bladder cancer (OR 0.38, 95% CI 0.19 to 0.78). The effects were more striking when IGF-1 and IGF binding protein-3 levels were analyzed together. In addition, a higher molar ratio of IGF-1-to-IGF binding protein-3 was associated with an increased risk of bladder cancer (OR 4.30, 95% CI 1.99 to 9.28). Dose-response relationships were evident when subjects were categorized into quartiles by the values of IGF-1, IGF binding protein-3 and the molar ratio in controls. To our knowledge this is the first study to suggest that patients with bladder cancer have higher plasma levels of IGF-1 and lower levels of IGF binding protein-3 than controls. Thus, measuring plasma IGF-1 and IGF binding protein-3 may be useful for assessing bladder cancer risk.