Cancer cachexia is associated with the IL10 -1082 gene promoter polymorphism in patients with gastroesophageal malignancy.
BACKGROUND
The genetic predisposition of the host to local or systemic inflammation may contribute to the effect of cancer cachexia.


OBJECTIVE
We investigated the relation between cytokine polymorphisms (IL1B -511, IL6 -174, IL10 -1082, TNFA -308, and LTA +252) and markers of nutritional status among patients with gastroesophageal cancer to determine whether any such association was reflected by cytokine concentrations in the tumor or plasma compartments.


METHODS
Patients (n = 203) with a diagnosis of gastroesophageal cancer underwent nutritional assessment (body mass index, anthropometric measures, dysphagia scoring, and estimation of dietary intake). Single nucleotide polymorphism genotyping was performed by TaqMan allelic discrimination genotyping. Serum cytokine and C-reactive protein concentrations were determined by enzyme-linked immunosorbent assay. Tumor tissue cytokine protein concentrations (n = 56) were determined by using the Cytometric Bead Array System.


RESULTS
IL10 GG and IL6 CC polymorphisms were associated with elevated serum C-reactive protein concentrations, and the IL6 CC genotype was also associated with elevated tumor tissue cytokine concentrations. At diagnosis, the IL10 GG, but not the IL6, genotype was linked with increased total weight loss: 4.9% for AA, 7.1% for AG, and 12.0% for GG (P = 0.007). Serum C-reactive protein concentrations correlated with increased weight loss (r = 0.24, P < 0.001). Compared with other genotypes, the IL10 GG genotype retained an independent association in determining the extent of weight loss on multivariate analysis (95% CI: 0.52, 3.43; P = 0.008). Possession of the GG allele was associated with a 2.3 times increased risk of developing cachexia (95% CI: 1.2, 4.3; P = 0.014).


CONCLUSIONS
These data suggest that the IL10 genotype of the host can influence the development of cachexia among patients with gastroesophageal malignancy.
Deans
D A Chris
DA
Department of Clinical and Surgical Sciences, Medical School, University of Edinburgh, Edinburgh, UK.
Tan
Benjamin H L
BH
Ross
James A
JA
Rose-Zerilli
Matthew
M
Wigmore
Stephen J
SJ
Howell
W Martin
WM
Grimble
Robert F
RF
Fearon
Kenneth C H
KC
D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002100:Cachexia / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015596:Nutrition Assessment; D009752:Nutritional Status; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000276:immunology* / Q000503:physiopathology
D016207:Cytokines; D016753:Interleukin-10; D002097:C-Reactive Protein