Ahirwar Dinesh, Mandhani Anil, Mittal Rama Devi
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Arch Med Res. 2009 Feb;40(2):97-102. doi: 10.1016/j.arcmed.2008.11.006.
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.
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).
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.
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.
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。
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。
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。
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。
