Aim: IGF binding protein-3 (IGFBP-3) displays growth inhibitory/proapoptotic action and counteracts the IGF-1 tumor-promoting effects by downregulating its bioavailability. We investigated whether IGFBP-3 SNPs determining high IGFBP-3 circulating levels are associated with improved survival of patients with advanced gastric cancer treated with palliative chemotherapy. Materials & methods: A total of 185 patients undergoing combination chemotherapy for relapsed/metastatic disease were considered eligible for the present clinical investigation. Four functional IGFBP-3 SNPs (rs3110697, rs2854746, rs2864744 and rs2960436) were studied for association with overall survival (OS). Results: In the multivariate model including SNPs and clinicopathologic features, the rs285744 A allele and the rs2960436 A allele showed favorable association with survival. The hazard ratios 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 hazard ratios 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 A/A genotype and the rs2960436 A/A genotype were 0.012 and 0.024, respectively. There was linkage disequilibrium between the four variants and there were four common haplotypes (>5% estimated frequency). The most common haplotype (GCAA) included all alleles causing IGFBP-3 upregulation and their carriers demonstrated the best outcome in the log-rank comparison of survival curves. Conclusion: 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.

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Published online 22 September 2010

Published in print September 2010

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Financial & competing interests disclosure

This research was supported by the Consorzio Interuniversitario per le Biotecnologie and Fanoateneo. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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