PMID-15110491 – IGF-1 and Cancer Risk: Systematic Review and Meta-Analysis
Renehan AG et al. "Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis," The Lancet, 2004;363(9418):1346-1353. doi:10.1016/S0140-6736(04)16044-3
Quick Reference
| Property | Value |
|---|---|
| PMID | 15110491 |
| DOI | 10.1016/S0140-6736(04)16044-3 |
| Year | 2004 |
| Journal | The Lancet |
| Study Type | Systematic Review / Meta-analysis |
| Evidence Level | I |
| Sample | 3,609 cancer cases across 21 studies |
| Peptide(s) Studied | GH-axis peptides (CJC-1295, Ipamorelin, Tesamorelin, Sermorelin, MK-677 — all peptides that elevate IGF-1) |
Key Findings
- Elevated circulating IGF-I levels are associated with increased risk of prostate cancer (OR 1.49, 95% CI 1.14-1.95)
- Elevated IGF-I associated with increased risk of premenopausal breast cancer (OR 1.65, 95% CI 1.26-2.08)
- Elevated IGF-I associated with increased risk of colorectal cancer (OR 1.49, 95% CI 1.11-2.01)
- No significant association found for lung cancer
- IGFBP-3 (IGF binding protein-3) showed independent associations with some cancer types
- Dose-response relationship observed: highest vs. lowest quintile comparisons showed the strongest associations
Study Design
Systematic review with meta-regression analysis of prospective and retrospective studies measuring circulating IGF-I and IGFBP-3 levels in relation to cancer risk. 21 studies included with 3,609 cancer cases. Meta-regression used to explore sources of heterogeneity including study design, assay type, and timing of blood draw relative to diagnosis.
Limitations
- Observational data; cannot establish causality between IGF-I levels and cancer
- Heterogeneity in IGF-I measurement assays across studies
- Single time-point IGF-I measurements may not reflect long-term exposure
- Confounders including diet, body composition, and physical activity variably controlled
- Does not directly address exogenous GH-stimulating peptides — the association is with endogenous IGF-I levels
Clinical Relevance
Foundational reference for GH-axis peptide cancer risk counseling. This Lancet meta-analysis is the most-cited evidence linking IGF-1 to cancer risk and is frequently referenced in discussions about GH secretagogues. However, it is critical to note that this study measures endogenous IGF-I levels, not the effect of exogenous GH-stimulating peptides, which produce transient and physiological IGF-1 elevations. Must be discussed alongside reassuring data from GH replacement studies (PMID-35368070, PMID-35319491) that show no increased cancer risk with supervised GH therapy.
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#research #systematic-review #evidence-level-I #cancer