Lack of association of the MDR1 C3435T polymorphism with susceptibility to gastric cancer and peptic ulcer: a systemic review and meta-analysis.

Dan-Dan Wu,Wei-Guo Dong,Jiao Li,Ji-Xiang Zhang

doi:10.7314/apjcp.2014.15.7.3021

Abstract

The multidrug resistance 1 gene (MDR1) C3435T polymorphism has been demonstrated to influence the P-glycoprotein (P-gp) activity level which is related to inflammation and carcinogenesis. This meta-analysis was performed to estimate the association between the MDR1 C3435T polymorphism and the risk of gastric cancer (GC) and peptic ulcer (PU). A literature search was conducted with PubMed, Embase and the Cochrane library up to November 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Data were analyzed using Review Manager (Version 5.2), and Stata package (version 12.0) for estimation of publication bias. Six case-control studies were included, of which five were for GC and two for PU. Overall, no evidence was found for any association between the MDR1 C3435T polymorphism and the susceptibility to GC and PU. In the stratified analysis by H. pylori infection status, stage and histology classification of GC, and PU type, there was still no significant association between them. This meta-analysis suggested that the MDR1 C3435T polymorphism is not associated with susceptibility to GC and PU. Large and well-designed studies are warranted to validate our findings.

Highlights

Peptic ulcer (PU), including gastric ulcer (GU) and duodenal ulcer (DU), remains a relatively common condition worldwide with annual incidence up to 0.19% (Sung et al, 2009), and patients with GU significantly increase the chance of developing gastric cancer (GC)
Inclusion and exclusion criteria Studies met the following criteria were included in our meta-analysis: (a) case-control study focused on association between multidrug resistance 1 gene (MDR1) C3435T polymorphism and risk to GC or peptic ulcer (PU), (b) contained available genotype frequency for both cases and controls, (c) all patients diagnosed with GC should be confirmed by pathological or histological examinations, (d) all patients diagnosed with PU had endoscopical and/or histological proofs, and (e) the H. pylori infection status was determined on the basis of histology, culture, urea breath test (UBT) or serum antibodies to H. pylori
The MDR1 C3435T polymorphism has been demonstrated for its role in regulating the P-glycoprotein (P-gp) activity level which is related to the inflammation and carcinogenesis (Johnstone et al, 2000; Ho et al, 2003; Mizutani et al, 2008)

Summary

Introduction

Peptic ulcer (PU), including gastric ulcer (GU) and duodenal ulcer (DU), remains a relatively common condition worldwide with annual incidence up to 0.19% (Sung et al, 2009), and patients with GU significantly increase the chance of developing gastric cancer (GC). The multidrug resistance 1 gene (MDR1) C3435T polymorphism has been demonstrated to influence the P-glycoprotein (P-gp) activity level which is related to inflammation and carcinogenesis. This meta-analysis was performed to estimate the association between the MDR1 C3435T polymorphism and the risk of gastric cancer (GC) and peptic ulcer (PU). No evidence was found for any association between the MDR1 C3435T polymorphism and the susceptibility to GC and PU. In the stratified analysis by H. pylori infection status, stage and histology classification of GC, and PU type, there was still no significant association between them. Conclusions: This meta-analysis suggested that the MDR1 C3435T polymorphism is not associated with susceptibility to GC and PU. Large and well-designed studies are warranted to validate our findings

Methods

Results

Conclusion