A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma
A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma
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DOI：
10.1016/s0016-5085(03)00899-0
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发表时间：
2003-08-01
期刊：
影响因子：
29.4
通讯作者：
Sobrinho-Simoes, M
中科院分区：
文献类型：
--
作者：
Machado, JC;Figueiredo, C;Sobrinho-Simoes, M
背景和目标：IL-1B和IL-1 RN基因的促炎性多态性与幽门螺杆菌感染者胃癌风险相关我们的目的是确定肿瘤坏死因子（TNF）-α基因变异与慢性萎缩性胃炎（CAG）和GC风险之间的关系。我们还研究了促炎基因多态性（IL-1B、IL-1 RN和TNF-α）的联合作用以及TNF-α和细菌基因型的联合作用各自影响这种风险的程度。研究方法：在包括306名对照、221名慢性胃炎患者和287名胃癌患者的病例对照研究中，TNF-α-308和IL-1B-511双等位基因多态性、IL-1 RN可变数目串联重复序列（VNTR）和H. pylori基因vacA（s和m区）和cagA基因分型。结果如下：我们发现TNF-α-308 *A等位基因携带者发生胃癌的风险增加，比值比（OR）为1.9（95%置信区间[CI]，1.3-2.7）。对于CAG和GC，发生疾病的几率随着高风险基因型的数量而增加。在3个位点携带高危基因型的个体发生CAG和GC的风险增加，OR分别为5.8（95%CI，1.1-31.0）和9.7（95%CI，2.6-36.0）。GC的风险不受细菌和TNF-α-308基因型组合的显著影响。结论：这些发现表明，TNF-α基因的促炎性多态性与GC风险增加相关，并且有可能定义与CAG和GC最高风险相关的特定遗传特征。
Background & Aims: Pro-inflammatory polymorphisms within the genes interleukin (IL)-1B and IL-1RN are associated with risk for gastric carcinoma (GC) in Helicobacter pylori-infected individuals. We aimed to determine the association between variation of the tumor necrosis factor (TNF)-alpha gene and the risk for chronic atrophic gastritis (CAG) and GC. We also investigated the extent to which the combined effect of proinflammatory genetic polymorphisms (IL-1B, IL-1RN, and TNF-alpha), and the combined effect of TNF-alpha and bacterial genotypes each influence such a risk. Methods: In a case-control study including 306 controls, 221 individuals with chronic gastritis, and 287 GC patients, the TNF-alpha-308 and IL-1B-511 bi-allelic polymorphisms, the IL-1RN variable number of tandem repeats (VNTR), and the H. pylori genes vacA (s and m regions) and cagA were genotyped. Results: We found that carriers of the TNF-alpha-308*A allele are at increased risk for GC development with an odds ratio (OR) of 1.9 (95% confidence interval [CI], 1.3-2.7). For both CAG and GC, the odds of developing disease increased with the number of high-risk genotypes. Individuals carrying high-risk genotypes at the 3 loci are at increased risk for CAG and GC with an OR of 5.8 (95% CI, 1.1-31.0) and 9.7 (95% CI, 2.6-36.0), respectively. The risk for GC was not affected significantly by the combination of bacterial and TNF-alpha-308 genotypes. Conclusions: These findings show that a proinflammatory polymorphism in the TNF-alpha gene is associated with increased risk for GC, and that it is possible to define a specific genetic profile associated with highest risk for CAG and GC.