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Variations in the interleukin-1 receptor antagonist gene impact on survival of patients with advanced colorectal cancer

The Pharmacogenomics Journal volume 9, pages 78–84 (2009)Cite this article

Abstract

The interleukin-1 receptor antagonist (IL-1RA) cytokine is thought to counteract tumor angiogenesis/metastasis. Two single nucleotide polymorphisms in the IL-1RA gene (rs4251961 T/C and rs579543 C/T) influence IL-1RA circulating levels with highest production in carriers of the homozygous rs4251961 T/T and rs579543 T/T genotypes. A total of 180 patients with metastatic colorectal cancer were categorized as high IL-1RA producers if they were carriers of at least one of the rs4251961 T/T or rs579543 T/T genotypes (T/T carriers). Median survival times were 35.8 months (95% confidence interval: 29.7–43.7 months) and 28.6 months (95% confidence interval: 25.6–30 months) in 56 T/T carriers and in 124 non-T/T carriers, respectively. The favorable association between T/T carriers’ status and survival was significant in the multivariate analysis (P=0.018). Also, T/T carriers and non-T/T carriers were prevalent among patients with Karnofsky performance status 90–100 and 70–80, respectively (P=0.002). These findings encourage additional studies in this field and the evaluation of a recombinant-IL-1RA for anticancer activity.

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Acknowledgements

This work was supported by funds from Consorzio Interuniversitario per le Biotecnologie (CIB) and Fanoateneo.

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Author notes

  1. F Graziano and A Ruzzo: Francesco Graziano and Annamaria Ruzzo contributed equally to the study.

Authors and Affiliations

  1. Medical Oncology Unit, Hospital of Pesaro, Pesaro, Italy

    F Graziano, V Catalano & P Alessandroni

  2. Department of Biomolecular Sciences, University of Urbino, Urbino, Italy

    A Ruzzo, E Canestrari, N Galluccio, P Maltese & M Magnani

  3. Department of Oncology, Azienda USL-6 Istituto Toscano Tumori, Livorno, Italy

    F Loupakis, A Falcone, A Fontana & G Masi

  4. Medical Oncology Unit, University Campus Biomedico, Rome, Italy

    D Santini, G Tonini & B Vincenzi

  5. Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy

    E Rulli & I Floriani

  6. Biochemistry Department, University of Otago, Dunedin, New Zealand

    B Humar

  7. Medical Oncology Unit, Hospital of Fermo, Fermo, Italy

    R Bisonni & L Giustini

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  1. F Graziano
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  14. V Catalano
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Correspondence to F Graziano.

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Graziano, F., Ruzzo, A., Canestrari, E. et al. Variations in the interleukin-1 receptor antagonist gene impact on survival of patients with advanced colorectal cancer. Pharmacogenomics J 9, 78–84 (2009). https://doi.org/10.1038/tpj.2008.16

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  • DOI: https://doi.org/10.1038/tpj.2008.16

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