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Elevated IGF-I levels correlate with increased risk of colorectal adenoma and colorectal cancerHigher IGF Levels Linked to Increased Risk of Colon Cancer

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Key Takeaway
Note that elevated IGF-I levels are associated with increased risks of colorectal cancer and advanced adenoma.

This meta-analysis examines the association between circulating levels of Insulin-Like Growth Factors (IGFs) peptides and IGF-binding proteins (IGFBP) with the risk of colorectal adenoma (CRA) and colorectal cancer (CRC). The analysis included 14,971 CRC cases and 38,124 CRA cases to evaluate these biomarkers.

Key findings indicate that elevated IGF-I is associated with an increased risk of CRC (OR = 1.16; 95% CI: 1.00-1.34), colon cancer (OR = 1.39; 95% CI: 1.22-1.57), and rectal cancer (OR = 1.29; 95% CI: 1.13-1.48). Additionally, IGF-I was associated with a 98% increment in advanced adenoma risk (OR = 1.98; 95% CI: 1.47-2.67). While IGF-II showed a borderline significant risk increment for CRC (OR = 1.37; 95% CI: 0.99-1.90) and a positive association with CRA (OR = 1.40; 95% CI: 1.05-1.86), the role of IGFBPs was less clear, showing a non-significant reduction for CRC but a significant reduction for CRA risk associated with IGFBP-1 (OR = 0.75; 95% CI: 0.56-0.99).

The authors note that further research is needed to clarify site-specific differences and the specific role of IGF-binding proteins. While these findings suggest the potential of the IGFs system as a biomarker for colorectal carcinogenesis, the evidence currently only establishes associations rather than causality.

How this fits prior evidence

This meta-analysis addresses a gap in identifying biomarkers for colorectal carcinogenesis by evaluating the IGF system. While previous coverage has identified gut microbiome signatures as robustly generalizable across ages and ctDNA/immune profiling as pathways for individualized treatment of recurrent CRC, this study focuses on the role of circulating growth factors as potential indicators of risk.

Researchers analyzed data from nearly 53,000 cases involving individuals with colorectal adenomas and colorectal cancer. The study looked at how certain proteins, known as Insulin-Like Growth Factors (IGFs), relate to the development of these conditions.

The findings show a link between higher levels of IGF-I and an increased risk of both colon and rectal cancers. Specifically, the data showed a significant increase in the risk of advanced adenomas associated with IGF-I. While some other proteins like IGF-II also showed links to certain risks, the results for others were less clear or not statistically significant.

It is important to note that this study shows an association between these protein levels and cancer risk, but it does not prove that the proteins cause the cancer. Because this is a large-scale data analysis, it serves as a tool for researchers to identify potential markers for early detection. You should speak with a doctor to understand what these findings mean for your personal health.

What this means for you:
Higher levels of certain growth factors are linked to an increased risk of colorectal cancer and polyps.

Common questions

What is the link between IGF-I and cancer?

The study found that higher levels of IGF-I are associated with an increased risk of colorectal cancer. Specifically, it showed a 1.39 increase for colon cancer and a 1.29 increase for rectal cancer. It also showed a significant 98% increase in the risk of advanced adenoma.

Are these findings enough to diagnose cancer?

No, these results show an association rather than a direct cause. The study suggests that the IGF system could be a potential biomarker for researchers to use in identifying risks, but it is not a replacement for standard medical screenings.

What other proteins were studied?

The study also looked at IGF-II and IGFBP-1. It found that IGF-II had a positive association with colorectal adenoma risk, while higher levels of IGFBP-1 were associated with a significant reduction in the risk of colorectal adenoma.

Study Details

Study typeMeta analysis
EvidenceLevel 1
PublishedAug 2026
View Original Abstract ↓
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.
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