Background: Host genetic variants causing high insulin growth factor binding protein-3 IGFBP-3 levels may counteract tumor-promoting pathways. In fact, IGFBP-3 displays growth inhibitory/pro-apoptotic actions and it regulates the insulin-like growth factor-1 (IGF-1) bioavailability. We investigated whether IGFBP-3 single nucleotide polymorphisms (SNPs) determining high IGFBP-3 circulating levels are also associated with improved survival of patients with advanced gastric cancer treated with palliative chemotherapy. Methods: The study population was assembled from 335 gastric cancer patients who were prospectively enrolled in two case-control studies for disease susceptibility. Patients undergoing combination chemotherapy for relapsed/metastatic disease were considered eligible for the present clinical investigation. Four functional IGFBP3 SNPs (rs3110697, rs2854746, rs2864744, rs2960436) were studied for association with overall survival (OS). Results: There were 185 assessable patients. In the multivariate model including SNPs and clinico-pathologicfeatures, the rs285744 A alleleand the rs2960436 A allelewereprotective with respecttothe riskofdeath ina dose-dependentmanner.Thehazardratios (HRs)with 95% confidence intervals (95%CIs) for rs285744 C/A and A/A genotypes were 0.38 (95%CI 0.18-0.66) and 0.20 (95%CI 0.09-0.39), respectively. The HRs and the 95%CIs for rs2960436 G/A and A/A genotypes were 0.41 (95%CI 0.25-0.68) and 0.35 (95%CI 0.16-0.58), respectively. Bonferroni-corrected p values for the rs285744 AA genotype and the rs2960436 A/A genotype were 0.012 and 0.024, respectively. Conclusions: Genetic regulation of the IGFBP-3 impacts on survival of patients with advanced gastric cancer. This finding deserves additional studies because of its prognostic and therapeutic implications

HOST GENETIC VARIANTS IN THE INSULIN GROWTH FACTOR BINDING PROTEIN-3 IMPACT ON SURVIVAL OF PATIENTS WITH ADVANCED GASTRIC CANCER TREATED WITH PALLIATIVE CHEMOTHERAPY

RUZZO, ANNAMARIA;MAGNANI, MAURO;
2010

Abstract

Background: Host genetic variants causing high insulin growth factor binding protein-3 IGFBP-3 levels may counteract tumor-promoting pathways. In fact, IGFBP-3 displays growth inhibitory/pro-apoptotic actions and it regulates the insulin-like growth factor-1 (IGF-1) bioavailability. We investigated whether IGFBP-3 single nucleotide polymorphisms (SNPs) determining high IGFBP-3 circulating levels are also associated with improved survival of patients with advanced gastric cancer treated with palliative chemotherapy. Methods: The study population was assembled from 335 gastric cancer patients who were prospectively enrolled in two case-control studies for disease susceptibility. Patients undergoing combination chemotherapy for relapsed/metastatic disease were considered eligible for the present clinical investigation. Four functional IGFBP3 SNPs (rs3110697, rs2854746, rs2864744, rs2960436) were studied for association with overall survival (OS). Results: There were 185 assessable patients. In the multivariate model including SNPs and clinico-pathologicfeatures, the rs285744 A alleleand the rs2960436 A allelewereprotective with respecttothe riskofdeath ina dose-dependentmanner.Thehazardratios (HRs)with 95% confidence intervals (95%CIs) for rs285744 C/A and A/A genotypes were 0.38 (95%CI 0.18-0.66) and 0.20 (95%CI 0.09-0.39), respectively. The HRs and the 95%CIs for rs2960436 G/A and A/A genotypes were 0.41 (95%CI 0.25-0.68) and 0.35 (95%CI 0.16-0.58), respectively. Bonferroni-corrected p values for the rs285744 AA genotype and the rs2960436 A/A genotype were 0.012 and 0.024, respectively. Conclusions: Genetic regulation of the IGFBP-3 impacts on survival of patients with advanced gastric cancer. This finding deserves additional studies because of its prognostic and therapeutic implications
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11576/2639693
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