Circulating level of Insulin-Like Growth Factors (IGFs) peptides and risk of colorectal adenoma and cancer: A systematic review and meta-analysis.

Several studies have reported an association between circulating levels of IGFs peptides and the risk of colorectal adenoma (CRA) and colorectal cancer (CRC), but results remain inconclusive. This study examines the precise association between circulating levels of these peptides and both CRA and CRC risk. A literature search was performed on PubMed, Web of Science, and Scopus up to February 5, 2026. The studies were selected according to the PICOS framework and quality was assessed using the Newcastle-Ottawa Scale (NOS). The meta-analysis was performed using a random-effects model on risk estimates (RR, OR, or HR). Heterogeneity and publication bias were evaluated using Cochran's Q/I² statistics and Egger/Begg tests, respectively. A total of 48 articles were included, involving 14,971 CRC cases (with 796,245 controls) and 38,124 CRA cases (with 320,433 controls). The main analysis showed an increased risk of colorectal (OR = 1.16; 95% CI: 1.00-1.34), colon (OR = 1.39; 95% CI: 1.22-1.57), and rectal cancer (OR = 1.29; 95% CI: 1.13-1.48) associated with IGF-I. A borderline significant + 37 CRC risk increment was observed for IGF-II (OR = 1.37; 95% CI: 0.99-1.90). A non-significant reduction in CRC risk was found in association with IGFBPs while a significant increment of CRC and colon cancer risk was noted in association with IGF-I/IGFBP-3 ratio. Regarding CRA, IGF-I was associated with a 98% increment of advanced adenoma risk (OR = 1.98; 95% CI: 1.47-2.67) while a positive association of CRA risk was observed with IGF-II (OR = 1.40; 95% CI: 1.05-1.86). CRA risk was significantly reduced in association with IGFBP-1 (OR = 0.75; 95% CI: 0.56-0.99). These results highlight the potential of the IGFs system as a biomarker for colorectal carcinogenesis, although further research is needed to clarify the site-specific differences and the role of IGF-binding proteins.