Interleukin-10 and interleukin-18 promoter polymorphisms in an Italian cohort of patients with undifferentiated carcinoma of nasopharyngeal type.
OBJECTIVE
Cytokines such as IL-10 and IL-18 seem to be involved in the inflammatory response of undifferentiated carcinoma of nasopharyngeal type (UCNT). The aim of this study was to evaluate the correlation between functional single nucleotide polymorphisms (SNPs) in the promoter region of IL-10 and IL-18 genes and the virological and clinical characteristics in a large case series of Caucasian patients suffering from UCNT, a tumor regularly associated with the Epstein Barr Virus (EBV).


METHODS
Eighty-nine patients with histologically confirmed UCNT and 130 healthy donors were included in our study. DNA was examined for the polymorphisms of IL-10 gene at positions -1082, -819, -592 by direct sequencing and IL-18 gene at position -607 and -137 by allele-specific PCR. EBV DNA serum viremia was evaluated by QC-PCR.


RESULTS
The distributions of the IL-10 and IL-18 genetic variants were not different between UCNT patients and healthy controls. The frequency of IL-10 -1082G allele, which is associated with high IL-10 expression, showed a nearly statistically significant increase in UCNT patients EBV DNA-negative as compared to healthy controls (OR=3.3 95% CI: 1.2-9.8). Subjects with C/C or C/G combined IL-18 genotypes showed an increased risk of being with Stages III-IV (OR=2.1 95% CI: 1.2-6.6).


CONCLUSIONS
This study was performed to improve the definition of the pathogenetic factors implicated in UCNT by addressing the correlation between cytokine polymorphisms and clinical parameters. This is the first study investigating the possible role of the IL-18 and IL-10 polymorphisms in the development and outcome of UCNT. In our genetic analysis there is no evidence for involvement of IL-10 promoter polymorphisms alone in the genetic predisposition to this tumor. On the other hand, IL18 genetic variants may represent a genetic risk factor for tumor aggressiveness.
Pratesi
Chiara
C
Microbiology, Immunology and Virology Unit, Centro di Riferimento Oncologico, 33081, Aviano, Italy.
Bortolin
Maria Teresa
MT
Bidoli
Ettore
E
Tedeschi
Rosamaria
R
Vaccher
Emanuela
E
Dolcetti
Riccardo
R
Guidoboni
Massimo
M
Franchin
Gianni
G
Barzan
Luigi
L
Zanussi
Stefania
S
Caruso
Calogero
C
De Paoli
Paolo
P
D002277:Carcinoma / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D015331:Cohort Studies; D020031:Epstein-Barr Virus Infections / Q000150:complications; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation; D016753:Interleukin-10 / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics*; D007558:Italy; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000821:virology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012307:Risk Factors
D016209:Interleukin-8; D016753:Interleukin-10