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-1beta 511, IL-6 174, IL-10 1082, TNFalpha 308 and LTalpha +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). TNFalpha 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, TNFalpha 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.
Deans
Chris
C
Cell Injury and Apoptosis Section, Tissue Injury and Repair Group, MRC Centre for Inflammation Research, Department of Clinical and Surgical Sciences, Medical School, Edinburgh University, Edinburgh, EH8 9AG, UK.
Rose-Zerilli
Matthew
M
Wigmore
Stephen
S
Ross
James
J
Howell
Martin
M
Jackson
Alan
A
Grimble
Robert
R
Fearon
Kenneth
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000401:mortality*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D013274:Stomach Neoplasms / Q000276:immunology* / Q000401:mortality*; D016019:Survival Analysis
D015415:Biomarkers; D016207:Cytokines; D002097:C-Reactive Protein