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

F. Graziano, A. Ruzzo, E. Canestrari, F. Loupakis, D. Santini, E. Rulli, B. Humar, N. Galluccio, R. Bisonni, I. Floriani, P. Maltese, A. Falcone, G. Tonini, V. Catalano, A. Fontana, L. Giustini, G. Masi, B. Vincenzi, P. Alessandroni, M. Magnani

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)78-84
Number of pages7
JournalPharmacogenomics Journal
Volume9
Issue number1
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics

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    Graziano, F., Ruzzo, A., Canestrari, E., Loupakis, F., Santini, D., Rulli, E., Humar, B., Galluccio, N., Bisonni, R., Floriani, I., Maltese, P., Falcone, A., Tonini, G., Catalano, V., Fontana, A., Giustini, L., Masi, G., Vincenzi, B., Alessandroni, P., & Magnani, M. (2009). Variations in the interleukin-1 receptor antagonist gene impact on survival of patients with advanced colorectal cancer. Pharmacogenomics Journal, 9(1), 78-84. https://doi.org/10.1038/tpj.2008.16