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白细胞介素-1β基因多态性与非裔美国人和高加索人胃癌前病变的关联

Association of interleukin-1beta gene polymorphisms with precancerous gastric lesions in African Americans and Caucasians.

作者信息

Zabaleta Jovanny, Camargo M Constanza, Piazuelo M Blanca, Fontham Elizabeth, Schneider Barbara G, Sicinschi Liviu A, Ferrante William, Balart Luis, Correa Pelayo, Ochoa Augusto C

机构信息

Department of Pathology, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.

出版信息

Am J Gastroenterol. 2006 Jan;101(1):163-71. doi: 10.1111/j.1572-0241.2006.00387.x.

Abstract

OBJECTIVE

Interleukin-1beta plays an important role in inflammation and gastric physiology. Polymorphisms of the IL1B gene have been associated with gastric atrophy and increased cancer risk, especially in Helicobacter pylori-infected subjects. The aim of this study was to evaluate the relationship between IL1B and IL1 receptor antagonist gene polymorphisms and the risk of multifocal atrophic gastritis in African Americans and Caucasians.

METHODS

Genomic DNA was extracted from gastric biopsies of 269 adult outpatients (172 African Americans and 97 Caucasians) undergoing diagnostic upper gastrointestinal endoscopy. Histological diagnosis was evaluated according to the updated Sydney System and H. pylori status was assessed by Steiner silver stain. Polymorphisms of the IL1B gene (-511, -31, and +3954) and the IL1 receptor antagonist were investigated by PCR-RFLP. Logistic regression models were used to identify variables associated with multifocal atrophic gastritis in terms of odds ratios and 95% confidence intervals.

RESULTS

Considering subjects with normal histology and nonatrophic gastritis as controls, a significant association was found between IL1B+3954T carrier and multiatrophic gastritis (OR 2.23, 95% CI 1.28, 3.88). Analyses stratified by ethnic group demonstrated similar associations in both African Americans (OR 2.23, 95% CI 1.14, 4.37) and Caucasians (OR 2.04, 95% CI 0.74, 5.65). A positive but not significant association was found between the allele 2 of the IL1RN and the presence of multifocal atrophic gastritis. The remaining proinflammatory polymorphisms were not associated with this precancerous lesion.

CONCLUSIONS

Our results suggest that the presence of IL1B+3954T allele is a risk marker for multifocal atrophic gastritis in the population studied.

摘要

目的

白细胞介素-1β在炎症和胃生理过程中发挥重要作用。IL1B基因多态性与胃萎缩及癌症风险增加相关,尤其是在幽门螺杆菌感染的个体中。本研究旨在评估IL1B和白细胞介素-1受体拮抗剂基因多态性与非裔美国人和高加索人多灶萎缩性胃炎风险之间的关系。

方法

从269例接受诊断性上消化道内镜检查的成年门诊患者(172例非裔美国人,97例高加索人)的胃活检组织中提取基因组DNA。根据更新的悉尼系统评估组织学诊断,并通过施泰纳银染色评估幽门螺杆菌感染状况。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法研究IL1B基因(-511、-31和+3954)和白细胞介素-1受体拮抗剂的多态性。采用逻辑回归模型,根据比值比和95%置信区间确定与多灶萎缩性胃炎相关的变量。

结果

将组织学正常和非萎缩性胃炎患者作为对照,发现IL1B+3954T携带者与多灶萎缩性胃炎之间存在显著关联(比值比2.23,95%置信区间1.28,3.88)。按种族分组分析显示,非裔美国人(比值比2.23,95%置信区间1.14,4.37)和高加索人(比值比2.04,95%置信区间0.74,5.65)中均存在类似关联。IL1RN的2等位基因与多灶萎缩性胃炎的存在之间存在正向但不显著的关联。其余促炎多态性与这种癌前病变无关。

结论

我们的结果表明,在所研究的人群中,IL1B+3954T等位基因的存在是多灶萎缩性胃炎的一个风险标志物。

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