Graziano F et al. (2005) Prognostic role of interleukin-1β gene and interleukin-1 receptor antagonist gene polymorphisms in patients with advanced gastric cancer. J Clin Oncol 23: 2339–2345

A recent study by Graziano and colleagues has investigated the prognostic role of interleukin-1β (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) genotypes in patients undergoing palliative treatment for advanced gastric cancer. The findings indicate that functional polymorphisms in these genes might affect prognosis, and that recombinant IL-1RN merits further study as a new therapy.

This prospective study included 123 patients with relapsed or metastatic gastric cancer, all of whom provided peripheral blood samples before starting cisplatin–fluorouracil-based palliative chemotherapy. Following DNA extraction, the investigators looked for IL-1B and IL-1RN polymorphisms known to be associated with gastric cancer risk, namely IL-1B-511C/T and IL-1B-31T/C (single nucleotide polymorphisms) and IL-1RN2 (variable number of tandem repeats in the second intron of IL-1RN). Patients were then grouped according to their IL-1B/IL-1RN genotypes and survival data were collected during a median follow-up of 14 months.

Wild-type genotypes were found in 34% of patients (group A), whereas the remainder were IL-1RN2 carriers with or without IL-1B polymorphisms (36%; group B) or had at least one IL-1B polymorphism and wild-type IL-1RN (30%; group C). Although chemotherapy response rates were similar in the three groups, progression-free survival and overall survival were significantly better in groups A and B than in group C. This suggests that the combination of IL-1B polymorphisms and wild-type IL-1RN has an adverse effect on prognosis in this setting.

The authors also discuss the potential role of recombinant human IL-1RN in the treatment of metastatic cancer, and recommend that patients should be stratified according to IL-1B/IL-1RN genotype.