Pratesi Chiara, Bortolin Maria Teresa, Bidoli Ettore, Tedeschi Rosamaria, Vaccher Emanuela, Dolcetti Riccardo, Guidoboni Massimo, Franchin Gianni, Barzan Luigi, Zanussi Stefania, Caruso Calogero, De Paoli Paolo
Microbiology, Immunology and Virology Unit, Centro di Riferimento Oncologico, 33081, Aviano, Italy.
Cancer Immunol Immunother. 2006 Jan;55(1):23-30. doi: 10.1007/s00262-005-0688-z. Epub 2005 Oct 27.
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).
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.
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).
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.
白细胞介素-10(IL-10)和白细胞介素-18(IL-18)等细胞因子似乎参与了鼻咽型未分化癌(UCNT)的炎症反应。本研究的目的是评估IL-10和IL-18基因启动子区域功能性单核苷酸多态性(SNP)与大量高加索UCNT患者(一种常与爱泼斯坦-巴尔病毒(EBV)相关的肿瘤)的病毒学和临床特征之间的相关性。
本研究纳入了89例经组织学确诊的UCNT患者和130名健康供体。通过直接测序检测IL-10基因在-1082、-819、-592位点的多态性,通过等位基因特异性PCR检测IL-18基因在-607和-137位点的多态性。通过定量聚合酶链反应(QC-PCR)评估EBV DNA血清病毒血症。
UCNT患者和健康对照之间IL-10和IL-18基因变异的分布没有差异。与高IL-10表达相关的IL-10 -1082G等位基因频率在EBV DNA阴性的UCNT患者中与健康对照相比有近乎统计学意义的增加(比值比(OR)=3.3,95%置信区间(CI):1.2-9.8)。具有C/C或C/G组合IL-18基因型的受试者处于III-IV期的风险增加(OR=2.1,95% CI:1.2-6.6)。
本研究旨在通过探讨细胞因子多态性与临床参数之间的相关性来完善对UCNT致病因素的定义。这是第一项研究IL-18和IL-10多态性在UCNT发生发展及预后中可能作用的研究。在我们的基因分析中,没有证据表明单独的IL-10启动子多态性参与了该肿瘤的遗传易感性。另一方面,IL18基因变异可能代表肿瘤侵袭性的一个遗传风险因素。