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胃癌中E-钙黏蛋白基因启动子区域的单核苷酸多态性:墨西哥年轻人群的病例对照研究

Single nucleotide polymorphisms in the promoter region of the E-cadherin gene in gastric cancer: case-control study in a young Mexican population.

作者信息

Medina-Franco Heriberto, Ramos-De la Medina Antonio, Vizcaino Gloria, Medina-Franco Jose Luis

机构信息

Department of Surgery, Section of Surgical Oncology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Vasco de Quiroga 15, Colonia Seccion XVI, Tlalpan, Mexico City, Mexico.

出版信息

Ann Surg Oncol. 2007 Aug;14(8):2246-9. doi: 10.1245/s10434-006-9054-4. Epub 2007 Jun 5.

DOI:10.1245/s10434-006-9054-4
PMID:17549573
Abstract

BACKGROUND

Gastric cancer has a tendency to present at early age in the Mexican population, and it is frequently associated with a family history. A polymorphism at position -160 at the CDH1 promoter region has been reported to lead to transcriptional downregulation of the gene in vitro, with possible increase in the risk of gastric cancer. We evaluated the role of the -160A allele in the risk of gastric cancer in a young Mexican population.

METHODS

Peripheral blood sample of Mexican patients younger than 45 years old with diagnosis of diffuse gastric cancer were obtained. We performed DNA extraction and analyzed the frequencies of -160 promoter polymorphism of E-cadherin gene by polymerase chain reaction-single strand conformational polymorphism. These frequencies were compared with those of healthy controls. The chi2 test for association was used to test differences of the genotype frequencies between normal controls and patients with gastric cancer. Findings were considered significant at P < .05.

RESULTS

The frequency of the -160 A allele was significantly higher (P = .002) in 39 patients with diffuse gastric cancer compared with 78 matched controls. The odds ratio associated with the A-allele was 1.98 for C/A heterozygotes (95% CI 1.01-3.98) and 6.5 for A/A homozygotes (95% CI 2.1-19.6). We found an increased risk of diffuse gastric cancer according to family history, independent of the expression of the polymorphism.

CONCLUSIONS

The -160 C/A polymorphism of the E-cadherin has a direct effect on the risk of diffuse gastric cancer at young age in Mexican population.

摘要

背景

在墨西哥人群中,胃癌倾向于在早年发病,且常与家族病史相关。据报道,CDH1启动子区域-160位点的多态性会导致该基因在体外转录下调,可能增加患胃癌的风险。我们评估了-160A等位基因在墨西哥年轻人群患胃癌风险中的作用。

方法

获取年龄小于45岁、诊断为弥漫性胃癌的墨西哥患者的外周血样本。我们进行DNA提取,并通过聚合酶链反应-单链构象多态性分析E-钙黏蛋白基因-160启动子多态性的频率。将这些频率与健康对照者的频率进行比较。采用卡方检验来检验正常对照者与胃癌患者之间基因型频率的差异。P <.05时的结果被认为具有统计学意义。

结果

与78名匹配的对照者相比,39名弥漫性胃癌患者中-160A等位基因的频率显著更高(P =.002)。C/A杂合子与A等位基因相关的优势比为1.98(95%可信区间1.01 - 3.98),A/A纯合子为6.5(95%可信区间2.1 - 19.6)。我们发现,无论多态性的表达如何,根据家族病史,弥漫性胃癌的风险都会增加。

结论

E-钙黏蛋白的-160 C/A多态性对墨西哥年轻人群患弥漫性胃癌的风险有直接影响。

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