Brief Article
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World J Gastroenterol. Apr 14, 2010; 16(14): 1788-1794
Published online Apr 14, 2010. doi: 10.3748/wjg.v16.i14.1788
Inflammatory cytokine gene polymorphisms increase the risk of atrophic gastritis and intestinal metaplasia
Zhong-Wu Li, Ying Wu, Yu Sun, Lu-Ying Liu, Meng-Meng Tian, Guo-Shuang Feng, Wei-Cheng You, Ji-You Li
Zhong-Wu Li, Ying Wu, Yu Sun, Lu-Ying Liu, Meng-Meng Tian, Ji-You Li, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China
Guo-Shuang Feng, Wei-Cheng You, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Epidemiology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China
Author contributions: Li ZW performed the majority of experiments and participated in the manuscript writing; Wu Y, Sun Y, Liu LY and Tian MM carried out part of the experiments; Feng GS performed the data analysis; You WC and Li JY designed the study and revised the manuscript.
Supported by The Grants from Beijing Municipal Science Foundation, the Key Technology Research and Development Program, No. 2002BA711A06, the National 973 Project, No. 1998051203 and 863 Project, No. 2006A402
Correspondence to: Ji-You Li, Professor, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China. lijiyou@263.net
Telephone: +86-10-88192450 Fax: +86-10-88192437
Received: December 16, 2009
Revised: January 20, 2010
Accepted: January 27, 2010
Published online: April 14, 2010
Abstract

AIM: To investigate the effects of interleukin-8 (IL-8), macrophage migration inhibitory factor (MIF) gene polymorphisms, Helicobacter pylori (H. pylori) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM).

METHODS: A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on an average follow-up period of 56 mo, the 372 cases were divided into no progression group (no histological progression from normal or superficial gastritis, n = 137), group I (progressed from normal or superficial gastritis to SCAG, n = 134) and group II (progressed from normal or superficial gastritis to IM, n = 101). IL-8, MIF gene polymorphisms were detected by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis and DNA sequencing.

RESULTS: An increased risk of SCAG was found in subjects with IL-8-251 AA genotype [odds ratio (OR) = 2.62, 95% CI: 1.23-5.72] or IL-8-251 A allele carriers (AA + AT) (OR = 1.81, 95% CI: 1.06-3.09). An elevated risk of IM was found in subjects with IL-8-251 AT genotype (OR = 2.27, 95% CI: 1.25-4.14) or IL-8-251 A allele carriers (OR = 2.07, 95% CI: 1.16-3.69). An increased risk of SCAG was found in subjects with MIF-173 GC genotype (OR = 2.36, 95% CI: 1.38-4.02) or MIF-173 C allele carriers (GC + CC) (OR = 2.07, 95% CI: 1.21-3.55). An elevated risk of IM was found in subjects with MIF-173 CC genotype (OR = 2.27, 95% CI: 1.16-4.46) or MIF-173 C allele carriers (OR = 3.84, 95% CI: 1.58-9.34). The risk of SCAG and IM was more evident in subjects carrying IL-8-251 A allele (OR = 6.70, 95% CI: 1.29-9.78) or MIF-173 C allele (OR = 6.54, 95% CI: 2.97-14.20) and positive for H. pylori infection.

CONCLUSION: IL-8-251 and MIF-173 gene polymorphisms are significantly associated with the risk of SCAG and IM in a population with a high risk of GC in Linqu County, Shandong Province, China.

Keywords: Chronic atrophic gastritis; Gene polymorphisms; Helicobacter pylori; Interleukin-8; Intestinal metaplasia; Macrophage migration inhibitory factor