启动子区域（rs2233408）的 IkappaBalpha 多态性影响中国人胃癌的易感性。

IkappaBalpha polymorphism at promoter region (rs2233408) influences the susceptibility of gastric cancer in Chinese.

机构信息

Institute of Digestive Disease and Department of Meddicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.

出版信息

BMC Gastroenterol. 2010 Feb 5;10:15. doi: 10.1186/1471-230X-10-15.

DOI:10.1186/1471-230X-10-15

PMID:20132559

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2829487/

Abstract

BACKGROUND

Nuclear factor of kappa B inhibitor alpha (I kappaB alpha) protein is implicated in regulating a variety of cellular process from inflammation to tumorigenesis. The objective of this study was to investigate the susceptibility of rs2233408 T/C genotype in the promoter region of I kappaB alpha to gastric cancer and the association of this polymorphism with clinicopathologic variables in gastric cancer patients.

METHODS

A population-based case-control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 564 gastric cancer patients and 566 healthy controls were enrolled in this study. rs2233408 genotypes in I kappaB alpha were analyzed by TaqMan SNP genotyping assay.

RESULTS

Both rs2233408 T homozygote (TT) and T heterozygotes (TC and TT) had significantly reduced gastric cancer risk (TT: OR = 0.250, 95% CI = 0.069-0.909, P = 0.035; TC and TT: OR = 0.721, 95% CI = 0.530-0.981, P = 0.037), compared with rs2233408 C homozygote (CC). rs2233408 T heterozygotes were significantly associated with reduced risk of intestinal-type gastric cancer with ORs of 0.648 (95% CI = 0.459-0.916, P = 0.014), but not with the diffuse or mix type of gastric cancer. The association between rs2233408 T heterozygotes and gastric cancer appeared more apparent in the older patients (age>40) (OR = 0.674, 95% CI = 0.484-0.939, P = 0.02). rs2233408 T heterozygotes was associated with non-cardiac gastric cancer (OR = 0.594, 95% CI = 0.411-0.859, P = 0.006), but not with cardiac gastric cancer. However, rs2233408 polymorphism was not associated with the prognosis of gastric cancer patients.

CONCLUSIONS

I kappaB alpha rs2233408 T heterozygotes were associated with reduced risk of gastric cancer, especially for the development of certain subtypes of gastric cancer in Chinese population.

摘要

背景

核因子 kappa B 抑制剂 alpha（I kappaB alpha）蛋白参与调控从炎症到肿瘤发生等多种细胞过程。本研究旨在探讨 I kappaB alpha 启动子区 rs2233408 T/C 基因型与胃癌易感性的关系，并分析该多态性与胃癌患者临床病理变量的相关性。

方法

本研究为 1999 年至 2006 年在中国广东省进行的基于人群的病例对照研究。共纳入 564 例胃癌患者和 566 例健康对照者。采用 TaqMan SNP 基因分型检测技术分析 I kappaB alpha 中的 rs2233408 基因型。

结果

与 rs2233408 C 纯合子（CC）相比，rs2233408 T 纯合子（TT）和 T 杂合子（TC 和 TT）均显著降低了胃癌的发病风险（TT：OR=0.250，95%CI=0.069-0.909，P=0.035；TC 和 TT：OR=0.721，95%CI=0.530-0.981，P=0.037）。rs2233408 T 杂合子与肠型胃癌的发病风险降低显著相关，OR 值为 0.648（95%CI=0.459-0.916，P=0.014），但与弥漫型或混合型胃癌无关。rs2233408 T 杂合子与胃癌的相关性在年龄较大的患者（>40 岁）中更为明显（OR=0.674，95%CI=0.484-0.939，P=0.02）。rs2233408 T 杂合子与非贲门胃癌相关（OR=0.594，95%CI=0.411-0.859，P=0.006），但与贲门胃癌无关。然而，rs2233408 多态性与胃癌患者的预后无关。