Polymorphism in IGFBP3 gene is associated with prostate cancer risk: an updated meta-analysis

Insulin-like growth factor-binding protein-3 (IGFBP3) is the major protein that binds with insulin-like growth factor-1 (IGF-1) and is considered to be involved in the development and progression of various cancers. We aimed to examine the association between prostate cancer (PCa) and the IGFBP3 gene-202A/C polymorphism.

A comprehensive search within PubMed, EMBASE, and Cochrane Library was conducted to identify all case-control studies up to October 30, 2015, for a meta-analysis. Pooled odds ratios (ORs) and the 95% confidence intervals (CIs) were calculated using the fixed or random effects model.

Eighteen studies including 10,538 cases and 10,078 controls were identified. Overall, the CC genotype of IGFBP3-202A/C polymorphism was associated with increased risk of PCa in homozygote comparison (CC vs AA - OR =1.16, 95% CI: 1.08-1.25) and in recessive model (CC vs AA+AC - OR =1.11, 95% CI: 1.04-1.17). In dominant model, the CC/AC genotypes also implicated an increased risk of PCa (CC+AC vs AA - OR =1.11, 95% CI: 1.05-1.19). The C allele of IGFBP3-202A/C polymorphism was the risk allele for PCa relative to the A allele (OR =1.09, 95% CI: 1.05-1.14). Further stratification analysis revealed that the association between -202A/C polymorphism and PCa risk among Caucasians, but not in other ethnicities, was statistically significant (recessive model, OR =1.10, 95% CI: 1.02-1.19). In addition, the IGFBP3-202A/C polymorphism was associated with PCa risk in both population-based and hospital-based studies in homozygote comparison, recessive model, and allele model.

Our meta-analysis indicates that the IGFBP3-202A/C polymorphism is associated with the risk of PCa, particularly in Caucasians, with the C allele being the risk allele for PCa.