Phenotypes and genotypes of insulin-like growth factor 1, IGF-binding protein-3 and cancer risk: evidence from 96 studies

Insulin-like growth factor 1 (IGF1) and its main binding protein, IGF-binding protein 3 (IGFBP3), play an important role in cancer development. Circulating levels and functional polymorphisms of IGF1 and IGFBP3 may be biomarkers of cancer development. However, the results of published studies remain conflicting rather than conclusive. We searched MEDLINE and EMBASE databases for all published studies related to circulating levels and polymorphisms of IGF1 and IGFBP3 and cancer risk. In all, 96 studies and over 110 000 subjects were available for this meta-analysis. Higher IGF1 circulating levels significantly increased 15% of cancer risk (odds ratio (OR), 1.15, 95% confidence interval (CI), 1.03-1.29), especially among prostate, pre-menopausal breast and colorectal cancer patients, whereas higher concentrations of IGFBP3 significantly decreased the risk of advanced prostate cancer by 56% (OR, 0.44, 95% CI, 0.25-0.77). Meanwhile, IGFBP3 -202CC genotype was associated with an increased risk of prostate cancer with borderline significance (OR, 1.18, 95% CI, 0.99-1.41). Genotype-phenotype correlation analyses showed that circulating levels of IGFBP3 could be modified by its promoter polymorphism A-202C (P<0.001). In conclusion, circulating levels of IGF1, IGFBP3 and IGFBP3 A-202C play a crucial role in carcinogenesis and could serve as susceptibility biomarkers for cancer development. European Journal of Human Genetics (2009) 17, 1668-1675; doi:10.1038/ejhg.2009.86; published online 3 June 2009