Wu Ming-Shiang, Wu Chun-Ying, Chen Chien-Jen, Lin Ming-Tsan, Shun Chia-Tung, Lin Jaw-Town
Department of Internal Medicine, National Taiwan University Hospital Taipei, Taiwan.
Int J Cancer. 2003 May 1;104(5):617-23. doi: 10.1002/ijc.10987.
The association of cytokine genotypes with gastric carcinoma (GC) may be influenced by environmental factors and varies among different populations. Few studies have addressed the impact of different cytokine genotypes on the development and progression of GC. We analyzed 11 functional polymorphisms in tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-4 and IL-10 genes in 220 Taiwanese Chinese with GC and in 230 healthy controls. The risk of genotypes was adjusted with confounding environmental risks. Our results revealed that the frequency of Helicobacter pylori infection [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.19-2.56], cigarette smoking (OR 2.02, 95% CI 1.38-2.95) and high IL-10 producer genotype (OR 2.67, 95% CI 1.29-5.50) was significantly increased in the entire GC patients. Among different subtypes of GC, a higher risk of developing diffuse type (OR 1.64, 95% CI 1.01-2.67) or cardia cancer (OR 2.44, 95% CI 1.13-2.67) was observed for the CT/CC genotype of IL-4 at the position -590, whereas the high IL-10 producer genotype was significantly linked with the risk of cardia cancer (OR 3.21, 95% CI 1.06-9.73) or advanced stage (OR 2.29, 95% CI 1.12-4.64). No association was noted between GC and controls in the distribution of IL-1 and TNF-alpha genotypes. Logistic regression analyses revealed that H. pylori infection (OR 1.7, 95% CI 1.14-2.52), cigarette smoking (OR 1.87, 95% CI 1.27--2.96) and IL-10 genotype (OR 2.54, 95% CI 1.24-5.61) are independent risks for GC. Independent effects of IL-10 genotype, H. pylori infection and cigarette smoking indicate that carcinogenesis of GC is influenced by a variety of host and environmental factors.
细胞因子基因型与胃癌(GC)的关联可能受环境因素影响,且在不同人群中存在差异。很少有研究探讨不同细胞因子基因型对GC发生发展的影响。我们分析了220例台湾GC患者和230例健康对照者肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1、IL-4和IL-10基因中的11个功能多态性。对基因型风险进行了混杂环境风险调整。我们的结果显示,在所有GC患者中,幽门螺杆菌感染频率[比值比(OR)1.7,95%置信区间(CI)1.19 - 2.56]、吸烟(OR 2.02,95% CI 1.38 - 2.95)和高IL-10产生者基因型(OR 2.67,95% CI 1.29 - 5.50)显著增加。在GC的不同亚型中,对于IL-4 -590位点的CT/CC基因型,发生弥漫型(OR 1.64,95% CI 1.01 - 2.67)或贲门癌(OR 2.44,95% CI 1.13 - 2.67)的风险更高,而高IL-10产生者基因型与贲门癌风险(OR 3.21,95% CI 1.06 - 9.73)或晚期(OR 2.29,95% CI 1.12 - 4.64)显著相关。在IL-1和TNF-α基因型分布方面,未发现GC与对照之间存在关联。逻辑回归分析显示,幽门螺杆菌感染(OR 1.7,95% CI 1.14 - 2.52)、吸烟(OR 1.87,95% CI 1.27 - 2.96)和IL-10基因型(OR 2.54,95% CI 1.24 - 5.61)是GC的独立风险因素。IL-10基因型、幽门螺杆菌感染和吸烟的独立作用表明,GC的致癌作用受多种宿主和环境因素影响。