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Open Access Research article

Genetic modulation of the interleukin 6 (IL-6) system in patients with advanced gastric cancer: a background for an alternative target therapy

Annamaria Ruzzo1*, Vincenzo Catalano2, Emanuele Canestrari3, Elisa Giacomini1, Daniele Santini4, Giuseppe Tonini4, Bruno Vincenzi4, Giammaria Fiorentini2, Mauro Magnani1 and Francesco Graziano2

Author Affiliations

1 Department of Biomolecular Sciences, University of Urbino, Urbino, Italy

2 Division of Medical Oncology, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, Pesaro, Italy

3 Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, USA

4 Division of Medical Oncology, University Campus Biomedico, Rome, Italy

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BMC Cancer 2014, 14:357  doi:10.1186/1471-2407-14-357

Published: 22 May 2014

Abstract

Background

IL-6 triggers oncogenic/angiogenic signals and the cytokine-dependent pro-cachexia cascade. The prognostic role of the functional IL-6 (promoter) rs1800795 and the IL-6R (receptor) rs8192284 single nucleotide polymorphisms (SNP) was studied in patients with advanced gastric cancer treated with palliative chemotherapy.

Methods

One-hundred-sixty-one patients were genotyped for rs1800795 and rs8192284 SNPs using polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) analysis assay. These results were studied for association with overall survival (OS).

Results

In 161 assessable patients, frequencies of rs1800795 G/G, G/C and C/C genotypes were 46%, 42% and 12%, respectively. Frequencies of rs8192284 A/A, A/C and C/C genotypes were 36%, 45% and 19%, respectively. Carriers of the rs1800795 G/G and rs8192284 C/C genotypes showed the worst OS. In the multivariate model, rs1800795 G/G (1.69 hazard ratio; 95% confidence interval 1.18-2.42), and rs8192284 C/C (1.78 hazard ratio; 95% confidence interval 1.12-2.83) confirmed an adverse prognostic impact.

Conclusions

In this population, genetic variants that up-regulate the IL-6 system showed impact on OS. This findings sustain the hypothesis that anti-IL-6 compounds deserve clinical studies as novel therapeutics in the palliative treatment of cancer patients.

Keywords:
Interleukin 6; Gastric cancer; Survival; Prognosis; Chemotherapy; Polymorphism