Prognostic role of interleukin-1B and interleukin-1-receptor antagonist polymorphisms in localized gastric cancer.

Abstract

10623 Background: Interleukin-1b (IL1b) and interleukin-1 receptor antagonist (IL1-RN) polymorphisms have been suspected to play a role in prognostication of advanced gastric cancer (GC). Here, we sought to determine the prognostic role of these polymorphisms in localized GC. Methods: 62 patients (pts) were enrolled in this prospectively planned analyses. Pts were treated with peri-operative neoadjuvant and adjuvant chemotherapy between 2006 and 2010. All pts signed written informed consent for genetic analyses. DNA for genotyping was extracted from whole blood samples. Genotyping was performed using PCR-based methods. The primary objective was to analyze the association between genotypes and clinical outcome measured by overall survival (OS). Results: Median age was 59 years. Majority of pts were male (81%). 86% of pts were treated with epirubicine in combination with cisplatin or oxaliplatin and 5-fluorouracil or capecitabine. 14% were treated without epirubicine. Pts were assigned to receive peri-operative treatment consisting of 3 neoadjuvant and 3 adjuvant chemotherapy cycles. Median OS of the whole study population was 32.0 months [95%CI (28.0;35.9)]. IL1bC-511T, IL1bT-31C and IL1-RN polymorphisms were in strong linkage disequilibrium. In fact, the wildtype genotype IL-1b-511CC genotype was observed exclusively in combination with the wt IL1b-31TT and vice versa and a strong correlation with the IL1-RN L/L genotype was observed. Wildtype genotypes were associated with favourable median OS. Multivariate cox regression analyses revealed following factors as independent prognosticators of OS: presence of N2 status with a HR of 5.6 [95%CI (1.5;21.1); p=0.01], age with a HR of 1.6 [95%CI (1.2;2.1); p<0.001] and presence of the IL1-RN L/L genotype with a HR of 0.2 [95%CI (0.1; 0.5), p=0.001]. Median OS in pts with the homozygous wt genotype IL1-RN L/L was not reached whereas median OS in 2/L or 2/2 pts was 32 months [95%CI (18.1;45.9); p=0.09; log-rank test]. Conclusions: Our results confirm the prognostic role of IL1b and IL1RN polymorphisms in localized GC. These polymorphisms might play a crucial role in the guidance of multimodal treatment of localized GC.