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白细胞介素-10基因G-1082A和C-819T多态性作为尿路上皮膀胱癌可能的分子标志物

Interleukin-10 G-1082A and C-819T polymorphisms as possible molecular markers of urothelial bladder cancer.

作者信息

Ahirwar Dinesh, Mandhani Anil, Mittal Rama Devi

机构信息

Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

出版信息

Arch Med Res. 2009 Feb;40(2):97-102. doi: 10.1016/j.arcmed.2008.11.006.

Abstract

BACKGROUND AND AIMS

Interleukin-10 (IL-10) is an immunosuppressive cytokine that may promote tumor growth and metastasis in later stages of cancer development. DNA sequence variations in IL-10 gene may lead to altered production and/or activity, and this can modulate an individual's susceptibility to urothelial bladder cancer (UBC). To test this hypothesis, we investigated the association of rs 1800896 and rs 3021097 polymorphisms in IL-10 gene and their haplotypes with the risk of UBC in a Northern Indian population.

METHODS

We analyzed two single nucleotide polymorphisms of IL-10 gene at G-1082A (rs 1800896) and C-819T (rs 3021097) in 214 histologically confirmed UBC patients and 385 matched controls by allele-specific polymerase chain reaction (AS-PCR).

RESULTS

IL-10 C-819T CT, TT genotypes and T carriers (CT + TT) had significant association with UBC susceptibility (OR 1.75, 95% CI 1.09-2.80; OR 1.81, 95% CI 1.09-3.01 and OR 1.77, 95% CI 1.14-2.75, respectively). Similarly, GA, AA genotypes and A carriers (G-1082A) demonstrated increased risk for UBC (OR 1.91, 95% CI 1.04-3.50; OR 2.01, 95% CI 1.08-3.74 and OR 1.95, 95% CI 1.09-3.50, respectively). TT (C-819T) and T carriers showed protective association with high-risk tumors; (OR 0.34, 95% CI 0.13-0.88 and OR 0.41, 95% CI 0.17-0.97, respectively). We did not observe any association of IL-10 polymorphisms with smoking habits and UBC risk.

CONCLUSIONS

The study suggested that the low-producing genotypes of IL-10 (C-819T and G-1082A) polymorphisms are associated with increased UBC risk. Individuals with (C-819T) TT genotype and T carriers, however, showed a protective association with high-risk tumors. Our data suggest that IL-10 G-1082A and C-819T polymorphisms may be used as a molecular marker of urothelial bladder cancer.

摘要

背景与目的

白细胞介素-10(IL-10)是一种免疫抑制细胞因子,在癌症发展后期可能促进肿瘤生长和转移。IL-10基因的DNA序列变异可能导致其产生和/或活性改变,进而调节个体患尿路上皮膀胱癌(UBC)的易感性。为验证这一假设,我们在印度北部人群中研究了IL-10基因中rs1800896和rs3021097多态性及其单倍型与UBC风险的关联。

方法

我们通过等位基因特异性聚合酶链反应(AS-PCR)分析了214例经组织学确诊的UBC患者和385例匹配对照中IL-10基因在G-1082A(rs1800896)和C-819T(rs3021097)位点的两个单核苷酸多态性。

结果

IL-10 C-819T的CT、TT基因型及T等位基因携带者(CT + TT)与UBC易感性显著相关(OR分别为1.75,95%CI 1.09 - 2.80;OR 1.81,95%CI 1.09 - 3.01;OR 1.77,95%CI 1.14 - 2.75)。同样,G-1082A的GA、AA基因型及A等位基因携带者患UBC的风险增加(OR分别为1.91,9�%CI 1.04 - 3.50;OR 2.01,95%CI 1.08 - 3.74;OR 1.95,95%CI 1.09 - 3.50)。TT(C-819T)基因型及T等位基因携带者与高危肿瘤呈保护性关联(OR分别为0.34,95%CI 0.13 - 0.88;OR 0.41,95%CI 0.17 - 0.97)。我们未观察到IL-10多态性与吸烟习惯及UBC风险之间存在任何关联。

结论

该研究表明,IL-10(C-819T和G-1082A)多态性的低产生基因型与UBC风险增加相关。然而,(C-819T)TT基因型个体及T等位基因携带者与高危肿瘤呈保护性关联。我们的数据表明,IL-10 G-1082A和C-819T多态性可作为尿路上皮膀胱癌的分子标志物。

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