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.
Variations in the interleukin-1 receptor antagonist gene impact on survival of patients with advanced colorectal cancer / 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. - In: PHARMACOGENOMICS JOURNAL. - ISSN 1470-269X. - 9:1(2009), pp. 78-84. [10.1038/tpj.2008.16]
Variations in the interleukin-1 receptor antagonist gene impact on survival of patients with advanced colorectal cancer
Santini D;
2009
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
