Host cytokine genotype is related to adverse prognosis and systemic inflammation in gastro-oesophageal cancer

Background: Systemic inflammation has been linked with reduced survival in cancer, however, the role of the host cytokine genotype versus tumour phenotype in the generation of this response is not clearly established. This study examined the relationship between cytokine polymorphisms (IL-1 beta 511, IL-6 174, IL-10 1082, TNF alpha 308 and LT alpha +252) and serum cytokine concentrations, serum CRP concentration and survival duration in patients with gastro-oesophageal malignancy. Methods: Two hundred and three newly diagnosed patients with gastric or oesophageal cancer had serum CRP and cytokine concentrations determined by ELISA. SNP genotyping was performed by Taqman allelic discrimination genotyping and compared with the genotype observed in 266 healthy volunteers. Clinico-pathological information was collected prospectively and survival duration was recorded. Results: Distribution of the cytokine genotypes was similar between patients and controls. The IL-6 174 CC and IL-10 1082 GG genotypes were associated with elevated serum CRP (P = .03, P = .01, respectively; Mann-Whitney U test) and sTNF-R (P = .015, P = .02) concentrations. These genotypes were also associated with reduced survival duration (P = .01, P = .047; log-rank test). TNF alpha AA genotype was also associated with reduced survival duration on univariate (P = .032) and multivariate analysis (P = .006, multivariate model), but not with inflammatory markers. No other cytokine polymorphisms were associated with systemic inflammatory markers or prognosis. Conclusions: There is a pro-inflammatory cytokine haplotype (IL-6 CC, IL-10 GG, TNF alpha AA) that is associated with adverse prognosis that may act, at least in part, through an inflammatory mediated mechanism. Determining patients' cytokine haplotype may improve prognostication and allow stratification for intervention studies.