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在日本人群中,前 microRNA 常见遗传变异与胃癌风险的关联。

Association between common genetic variants in pre-microRNAs and gastric cancer risk in Japanese population.

机构信息

Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.

出版信息

Helicobacter. 2010 Dec;15(6):524-31. doi: 10.1111/j.1523-5378.2010.00806.x.

DOI:10.1111/j.1523-5378.2010.00806.x
PMID:21073609
Abstract

BACKGROUND

Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human cancers. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (miR-196a2, miR-146a, and miR-499) with the risk of gastric cancer (GC) and peptic ulcer diseases, and with the severity of Helicobacter pylori-induced gastritis in Japanese population.

METHODS

The rs11614913 (C>T), rs2910164 (G>C), and rs3746444 (A>G) SNPs were genotyped in 552 GC, and 697 non-cancer subjects, including 141 gastric and 73 duodenal ulcer, and 483 non-ulcer subjects. The degree of histologic gastritis was classified according to the updated Sydney System, and the serum pepsinogen levels were measured in selected 579 and 204 cases.

RESULTS

The rs2910164 CC genotype held a significantly higher risk of GC when compared to non-cancer subjects (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.02-1.66, p =.03). Similarly, the rs2910164 C carrier was associated with higher risk of GC when compared to both non-cancer and non-ulcer subjects (OR = 1.39, 95%CI = 1.00-1.93, p =.05, adjusted OR = 1.57, 95%CI = 1.09-2.27, p =.016, respectively). The rs2910164 CC genotype was associated with non-cardia and upper third, diffuse type and advanced stage GC. The rs11614913 TT genotype was associated with higher degree of mononuclear cell infiltration (score 0-1 vs 2∼, adjusted OR = 1.62, 95%CI = 1.05-2.49, p =.03).

CONCLUSIONS

The rs2910164 (G>C) SNP in the miR-146a is associated with susceptibility to GC. In addition, the rs11614913 (C>T) SNP in the miR-196a2 is associated with the degree of H. pylori-induced mononuclear cell infiltration.

摘要

背景

已经证明,常见的单核苷酸多态性(SNP)在 microRNA(miRNA)中与几种人类癌症的易感性有关。我们评估了前 miRNA(miR-196a2、miR-146a 和 miR-499)中三个 SNP(rs11614913、rs2910164 和 rs3746444)与胃癌(GC)和消化性溃疡病的风险以及与日本人群中幽门螺杆菌引起的胃炎严重程度的关联。

方法

在 552 例 GC 和 697 例非癌症患者中,包括 141 例胃溃疡和 73 例十二指肠溃疡以及 483 例非溃疡患者中,对 rs11614913(C>T)、rs2910164(G>C)和 rs3746444(A>G)SNP 进行了基因分型。根据更新的悉尼系统对组织学胃炎的程度进行分类,并在选定的 579 例和 204 例病例中测量了血清胃蛋白酶原水平。

结果

与非癌症患者相比,rs2910164 CC 基因型的 GC 风险显著更高(调整后的优势比(OR)=1.30,95%置信区间(CI)=1.02-1.66,p=.03)。同样,与非癌症和非溃疡患者相比,rs2910164 C 携带者的 GC 风险更高(OR=1.39,95%CI=1.00-1.93,p=.05,调整后的 OR=1.57,95%CI=1.09-2.27,p=.016,分别)。rs2910164 CC 基因型与非贲门和上三分之一、弥漫型和晚期 GC 相关。rs11614913 TT 基因型与单核细胞浸润程度较高(评分 0-1 与 2∼,调整后的 OR=1.62,95%CI=1.05-2.49,p=.03)有关。

结论

miR-146a 中的 rs2910164(G>C)SNP 与 GC 的易感性有关。此外,miR-196a2 中的 rs11614913(C>T)SNP 与幽门螺杆菌引起的单核细胞浸润程度有关。

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