Prognostic role of interleukin-1β gene and interleukin-1 receptor antagonist gene polymorphisms in patients with advanced gastric cancer

Purpose A high interleukin-1 beta 0 (IL-1 B) 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-IRNlong/2) enhance the circulating levels of the two cytokines. The prognostic role of IL-1B/1L-1RN genotypes was investigated in patients with relapsed and metastatic gastric cancer treated with palliative chemotherapy. Patients and Methods Before starting palliative chemotherapy, 123 prospectively enrolled patients supplied peripheral-blood samples for DNA extraction. Survival data were analyzed according to IL-IRN/IL-1B genotypes. Results Forty-two patients showed wild-type genotypes (IL-1RNlong/long, IL-1B-511C/C, and IL-IB-31T/7; group A). Forty-five patients showed the IL-IRN2 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-1B511C/T and/or IL-1B-37T/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). Conclusion In patients with advanced gastric cancer, IL-1B polymorphisms showed adverse prognostic influence when coupled with wild-type IL-7RN genotype. These findings deserve further investigation for potential anticancer activity of recombinant IL-RN.