The role of IGFBP3 functional polymorphisms in the risk of gastric cancer in a high-risk Chinese population

Insulin-like growth factors (IGFs) and their receptors play a crucial role in regulating cell proliferation, differentiation, and apoptosis. Insulin-like growth factor-binding protein-3 is the most abundant insulin-like growth factor receptor in the serum and binds the majority of insulin-like growth factors. Studies reported that circulating level of insulin-like growth factor-binding protein-3 was modulated by functional genetic variants of insulin-like growth factorbinding protein-3 and, therefore, maybe associated with the risk of gastric cancer. In this case-control study of 576 gastric cancer cases and 647 cancer-free control participants in a high-risk Chinese population, we tested the hypothesis that functional polymorphisms A-202C and Gly32Ala of insulin-like growth factor-binding protein-3 are associated with risk of gastric cancer. We found that the variant 32Ala allele was associated with a significantly increased risk of gastric cancer (adjusted odds ratio= 1.84, 95% confidence interval= 1.45-2.33 for 32Gly/Ala and odds ratio = 2.39, 95% confidence interval = 1.47-3.90 for 32Ala/Ala, respectively), compared with the wild-type homozygote 32Gly/Gly. Although the A-202C variant was not significantly associated with gastric cancer risk in the single locus analysis, we found a significant locus-locus interaction between insulin-like growth factor-binding protein-3 A-202C and Gly32Ala loci on gastric cancer risk (P-int<0.001). These findings suggest that functional variants of insulin-like growth factor-binding protein-3 might be important markers for gastric cancer susceptibility and further studies are warranted to characterize the functional relevance of the locus-locus interaction of this gene.