Allele 2 of the interleukin-1 receptor antagonist gene is associated with early gastric cancer
Allele 2 of the interleukin-1 receptor antagonist gene is associated with early gastric cancer
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DOI：
10.1200/jco.2004.03.034
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发表时间：
2004-12-01
影响因子：
45.3
通讯作者：
Folwaczny, C
中科院分区：
文献类型：
--
作者：
Glas, J;Török, HP;Folwaczny, C
目的研究白细胞介素-1（IL-1）基因簇多态性与进展期胃癌（T2-T4）的关系。在早期胃癌中，我们定义为局限于粘膜或粘膜下层的腺癌，（T1期），宿主遗传易感性的作用仍有待确定。患者和方法88例早期胃癌患者（阶段T1，77例幽门螺杆菌阳性）和145例对照者进行IL-1基因簇和肿瘤坏死因子α（TNF-A）多态性基因分型。基因结果IL-1 RN *2/2基因纯合型与早期胃癌密切相关（P <0.0001），而与IL-1基因簇的进一步相关性未观察到。TNF-A-308 A等位基因与弥漫型早期胃癌的弱相关性，以及与两个或三个促炎性基因多态性的复合物的相关性，其倾向于增加促炎性细胞因子IL-1 β和TNF-alpha的产生，也可以被证明。与晚期胃癌相反，进一步的促炎细胞因子多态性并不独立相关，但可能联合作用，反映了幽门螺杆菌定植宿主胃癌发生的早期步骤。然而，这些发现有待在未来的试验中得到证实，并应通过基因表达研究加以强调。(C)2004年美国临床肿瘤学会
Purpose In advanced gastric cancer (tumor stages T2-T4), associations with polymorphisms of the interleukin-1 (IL-1) gene cluster have been made. In early-stage gastric cancer, which we defined as adenocarcinoma confined to the mucosa or submucosa (stage T1), the role of host genetic susceptibility remains to be determined.Patients and Methods Eighty-eight patients with early-stage gastric cancer (stage T1, 77 positive for Helicobacter pylon) and 145 controls were genotyped for polymorphisms in the IL-1 gene cluster and the tumor necrosis factor alpha (TNF-A) gene. Statistical analysis was performed using the chi(2) test and the Fisher's exact test, respectively.Results The homozygous genotype IL-1RN*2/2 of the IL-RN gene was strongly associated with early-stage gastric cancer (P < .0001), whereas further associations with the IL-1 gene cluster were not observed. A weak association of the TNF-A-308A allele with the diffuse type of early-stage gastric cancer, and an association with a composite of two or three proinflammatory polymorphisms, which predispose to increased production of the proinflammatory cytokines IL-1beta and TNF-alpha, could also be demonstrated.Conclusion The genotype IL-1RN*2/2 seems to be associated with early-stage gastric cancer. As opposed to advanced-stage gastric cancer, further proinflammatory cytokine polymorphisms were not associated independently, but might act in combination and mirror early steps of gastric carcinogenesis in hosts colonized by Helicobacter pylori. However, these findings await confirmation in future trials and should be underscored by gene expression studies. (C) 2004 by American Society of Clinical Oncology