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

C Deans, M Rose-Zerilli, S Wigmore, J Ross… - Annals of surgical …, 2007 - Springer
C Deans, M Rose-Zerilli, S Wigmore, J Ross, M Howell, A Jackson, R Grimble, K Fearon
Annals of surgical oncology, 2007Springer
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-1β 511, IL-6 174, IL-10 1082, TNFα 308 and LTα+ 252) and
serum cytokine concentrations, serum CRP concentration and survival duration in patients
with gastro-oesophageal malignancy. Methods Two hundred and three newly diagnosed …
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-1β 511, IL-6 174, IL-10 1082, TNFα 308 and LTα +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). TNFα 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, TNFα 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.
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