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.

Measurement of insulin-like growth factor axis does not enhance specificity of PSA-based prostate cancer screening.

OBJECTIVES: To examine whether measurement of insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein (IGFBP)-2 or IGFBP-3, alone or in combination, enhanced the specificity of prostate cancer detection among men with a prostate-specific antigen (PSA) level of 3 ng/mL or greater beyond that achieved by the free/total PSA index. METHODS: Cross-sectional analysis was performed on blood samples taken from 597 asymptomatic men (79% of those biopsied) participating in a community case-finding exercise. All men had a total PSA level of 3 ng/mL or greater and had undergone prostate biopsy. Assays of IGF-I, IGF-II, IGFBP-2, IGFBP-3, and free and total PSA were performed. The predictive performance of a range of measures was assessed using receiver operating characteristic analyses and compared with the free/total PSA index, for all biopsies and for men with a PSA level of 3 to 10 ng/mL. The overall test performance was summarized using the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 597 men, 185 (31.0%) had prostate cancer identified at biopsy. When all biopsies were included, the performance of the free/total PSA index (AUC 0.73) was significantly greater than for IGF-I (AUC 0.59; P <0.0001), IGF-I/PSA ratio (AUC 0.65; P = 0.002), IGF-I + IGFBP-3 (AUC 0.59; P <0.0001), IGF-II (AUC 0.66; P = 0.002), and IGF-II + IGFBP-3 (AUC 0.67; P = 0.05). The combined measurement of free/total PSA, IGF-II, and IGFBP-3 resulted in a slight improvement in performance (AUC 0.76; P = 0.01). The results were similar when the analyses were restricted to men with an initial PSA level of 3 to 10 ng/mL. CONCLUSIONS: We found no evidence that measurement of the IGF axis enhances the specificity of prostate cancer detection in clinical practice beyond that achievable using the free/total PSA index.