Abstract
OBJECTIVE: To systematically evaluate the epidemiological association between serum insulin-like growth factor-1 (IGF-I) levels and the risk of prostate cancer, in order to provide evidence-based support for risk stratification and early prevention of prostate cancer. METHODS: In accordance with the PRISMA statement, major domestic and international databases were systematically searched. Cohort studies, case-control studies, and Mendelian randomization studies reporting the relationship between serum IGF-I and prostate cancer risk were included. A random-effects model was used to combine effect estimates, assess heterogeneity, and perform subgroup analysis and meta-regression. Sensitivity analysis and publication bias tests were used to evaluate the robustness of the results, and the GRADE system was used to assess the quality of evidence. RESULTS: A total of 16 studies involving multiple countries were included. The combined analysis showed that higher serum IGF-I levels were associated with an increased risk of prostate cancer (OR = 1.10, 95% CI: 1.02-1.18, P = 0.0136), with moderate heterogeneity (I²=50.6%). Subgroup analysis indicated that the association was more prominent in studies published in the last decade and in nested case-control designs, but heterogeneity was higher in large-sample and multicenter studies. Meta-regression analysis did not find that mean age or IGF-I levels significantly explained the heterogeneity. Sensitivity and publication bias analyses both supported the robustness of the main conclusion, and the GRADE assessment indicated moderate quality of evidence. CONCLUSION: Higher serum IGF-I levels are epidemiologically associated with an increased risk of prostate cancer, but the dose-response relationship is still unclear, and the correlation is susceptible to study characteristics and confounding factors. IGF-I is expected to be a potential biomarker for prostate cancer risk stratification. It is recommended that more high-quality studies be conducted in the future to verify its clinical application value. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420251174259.