Screen-detected prostate cancer and the insulin-like growth factor axis: Results of a population-based case-control study

Higher circulating levels of IGF-I have been associated with increased risk of prostate and some other cancers. Most research on prostate cancer has been based on men with symptoms or identified following treatment of benign disease. However, increasing numbers of cancer cases are now detected in asymptomatic men following prostate-specific antigen (PSA) tests. We therefore used a population-based case-finding exercise using the PSA test to examine whether associations between the IGF axis and cancer risk were apparent in this population. A matched case-control study was conducted among 7,383 men (50-70 years) receiving a PSA test as part of a case-finding exercise. Assays of IGF-I, IGF-II IGFBP-2 and IGFBP-3 were performed on cases and 2 controls matched on age, recruitment center and calendar time. Analyses were based on 176 cases and 324 matched controls. The risk of prostate cancer increased across quartiles of IGF-I (highest vs. lowest quartile, OR = 2.34; 95% CI = 1.26-4.34; P _trend = 0.02) and IGF-II (OR = 1.78; 95% CI = 0.94-3.15; P _trend = 0.09). Controlling for smoking history and IGFBP-3 strengthened associations with cancer for both IGF-I (OR = 3.00; 95% CI = 1.50-6.01; P_trend 0.005) and IGF-II (OR = 2.02; 95% CI = 1.07-3.84; P_trend = 0.04) Associations between the IGFs and cancer risk were stronger for advanced cases. Our findings suggest that both IGF-I and IGF-II are associated with an increased risk of screen-detected prostate cancer.