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Graziano, Francesco; Ruzzo, Annamaria; Santini, Daniele; Humar, Bostjan; Tonini, Giuseppe; Catalano, Vincenzo; Berardi, Rossana; Pizzagalli, Francesca; Arduini, Federica; Bearzi, Italo; Scartozzi, Mario; Cascinu, Stefano; Testa, Enrica; Ficarelli, Rita; Magnani, Mauro

Prognostic Role of Interleukin-1β Gene and Interleukin-1 Receptor Antagonist Gene Polymorphisms in Patients With Advanced Gastric Cancer

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  • Medientyp: E-Artikel
  • Titel: Prognostic Role of Interleukin-1β Gene and Interleukin-1 Receptor Antagonist Gene Polymorphisms in Patients With Advanced Gastric Cancer
  • Beteiligte: Graziano, Francesco; Ruzzo, Annamaria; Santini, Daniele; Humar, Bostjan; Tonini, Giuseppe; Catalano, Vincenzo; Berardi, Rossana; Pizzagalli, Francesca; Arduini, Federica; Bearzi, Italo; Scartozzi, Mario; Cascinu, Stefano; Testa, Enrica; Ficarelli, Rita; Magnani, Mauro
  • Erschienen: American Society of Clinical Oncology (ASCO), 2005
  • Erschienen in: Journal of Clinical Oncology
  • Sprache: Englisch
  • DOI: 10.1200/jco.2005.02.345
  • ISSN: 0732-183X; 1527-7755
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec><jats:title>Purpose</jats:title><jats:p> A high interleukin-1β (IL-1B) and interleukin-1 receptor antagonist (IL-RN) ratio underlies an unfavorable proinflammatory status. Also, it seems to be involved in the mechanisms of cancer cachexia and tumor angiogenesis and metastasis. Two single nucleotide polymorphisms in IL-1B gene (IL-1B-511C/T,IL-1B-31T/C) and a variable number of tandem repeat polymorphisms in IL-RN gene (IL-1RNlong/2) enhance the circulating levels of the two cytokines. The prognostic role of IL-1B/IL-1RN genotypes was investigated in patients with relapsed and metastatic gastric cancer treated with palliative chemotherapy. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> Before starting palliative chemotherapy, 123 prospectively enrolled patients supplied peripheral-blood samples for DNA extraction. Survival data were analyzed according to IL-1RN/IL-1B genotypes. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Forty-two patients showed wild-type genotypes (IL-1RNlong/long, IL-1B-511C/C, and IL-1B-31T/T; group A). Forty-five patients showed the IL-1RN2 polymorphism, with wild-type IL-1B genotypes in seven patients and with IL-1B-511C/T and/or IL-1B-31T/C polymorphisms in 38 patients (group B). The remaining 36 patients demonstrated wild-type IL-1RN, with IL-1B-511C/T and/or IL-1B-31T/C polymorphisms (group C). In group A and B patients, the median progression-free survival (PFS) was 25 and 26 weeks, respectively, and median overall survival (OS) was 42 and 43 weeks, respectively. Group C patients showed worse PFS (median, 16 weeks) and OS (median, 28 weeks) than group A (P = .006 for PFS; P = .0001 for OS) and group B patients (P = .01 for PFS; P = .0001 for OS). The long/T/C haplotype was overrepresented in patients with shortened PFS (P = .001) and OS (P = .0005). </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> In patients with advanced gastric cancer, IL-1B polymorphisms showed adverse prognostic influence when coupled with wild-type IL-1RN genotype. These findings deserve further investigation for potential anticancer activity of recombinant IL-RN. </jats:p></jats:sec>
  • Zugangsstatus: Freier Zugang