Insulin-like growth factors (IGFs) and IGF binding proteins in PSA-detected prostate cancer: a large population-based case-control study
Session type: Proffered paper sessions
Several studies have investigated associations of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with prostate cancer risk. These are generally small, comprising either clinically-detected or a mixture of clinically- and screen-detected cancer; and results have been inconsistent. With more cancers now being detected in asymptomatic men via prostate-specific antigen (PSA) testing, the involvement of the IGF system is of increasing interest.
Cross-sectional case-control study nested within a population-based sample of 111,000 men (aged 50-69) receiving PSA tests in the community-based ProtecT trial of prostate cancer treatments (ProtecT Study). Of 3,174 with prostate cancer, 2,686 provided serum samples at recruitment, along with a random sample of 2,766 age- and GP-matched controls. Cancers were mainly localized (n=2,355) and low grade (Gleason score<7) (n=1,808). IGF-I, IGF-II, IGFBP-2 and IGFBP-3 assays were performed on these serum samples.
IGF-I was not related to prostate cancer (OR* 0.99, 95% CI: 0.93,1.04) (ptrend=0.62). There was a positive association of IGF-II (OR* 1.16; 1.08,1.24) (ptrend <0.001), IGFBP-2 (OR* 1.18; 1.06,1.31) (ptrend<0.01) and IGFBP-3 (OR* 1.27; 1.19,1.36) (ptrend <0.001) with prostate cancer. IGF-I was inversely related to cancer after adjustment for IGFBP-3 (OR* 0.85; 0.79,0.91) (ptrend <0.001). IGFBP-3 remained positively associated after adjustment for IGF-I (OR* 1.42; 1.32,1.53) (ptrend <0.001). There was some evidence that IGF-I was positively associated with localised cancer (after IGFBP-3 adjustment, OR* 1.12; 0.97,1.31) but IGFBP-2 was positively associated with advanced cancer (OR* 1.10; 0.97,1.26). IGF-II and IGFBP-3 associations did not differ by stage or grade.
*OR per standard deviation increase in IGF/IGFBP
IGF-I was unrelated, whilst IGF-II, IGFBP-2 and IGFBP-3 were positively related, to PSA-detected prostate cancer in this population-based study, the largest in the world. This contrasts smaller studies, and suggests that the role of the IGF system may differ according to whether cancers are PSA- or clinically-detected.