A 5′-flanking region polymorphism in toll-like receptor 4 is associated with gastric cancer in a Chinese population

Hua Huang,Juan Wu,Guangfu Jin,Hanze Zhang,Yanbing Ding,Zhaolai Hua,Yan Zhou,Yan Xue,Yan Lu,Zhibin Hu,Yaochu Xu,Hongbing Shen

doi:10.1016/s1674-8301(10)60017-6

Abstract

Objective Inflammation induced by H.pylori colonization in the stomach is related to the development of gastric cancer and the genetic variations of the genes involved in the immune responses modify the host response to the infection. The aim of this study was to evaluate whether polymorphisms in the toll-like receptor 4 (TLR4) gene, a key regulator of both innate and adaptive immunity, were related to the susceptibility to gastric cancer in a Chinese population. Methods Two variations in the 5′-flanking region of TLR4 (rs1927914 T > C and rs10759932 T > C) were genotyped by using the PCR-restriction fragment length polymorphism (RFLP) assay in a case-control study of 1,053 incident gastric cancer cases and 1,100 cancer-free controls in a Chinese population. Results Individuals carrying the C allele of rs10759932 had a significantly reduced risk of gastric cancer (adjusted OR = 0.81; 95%CI = 0.67-0.96), compared with the wild-type homozygote (TT), and the protective effect was not significantly different among subgroups stratified by age, sex, smoking, drinking and H.pylori infection status ( P for heterogeneity > 0.05). No significant association was observed between rs1927914 and gastric cancer risk in this study population. Conclusion The T to C allele substitution of rs10759932 may play a protective role in gastric carcinogenesis in a Chinese population. Large studies with different ethnic populations are warranted to confirm these findings.

Highlights

Helicobacter pylori (H. pylori), a gram-negative microaerophilic bacterium, mainly colonizes the human stomach and induces various gastric lesions, ranging from gastritis to cancer
0.50 a Adjusted for age, sex, smoking and drinking status. In this case-control study of gastric cancer, we investigated the associations of two single nucleotide polymorphisms (SNPs) in the 5'-flanking region of toll-like receptor 4 (TLR4) with the risk of gastric cancer in a Chinese population
For the first time, that rs10759932 variant genotypes (TC/CC) of the TLR4 gene were associated with a significantly reduced risk of gastric cancer in this high-risk population

Summary

Introduction

Helicobacter pylori (H. pylori), a gram-negative microaerophilic bacterium, mainly colonizes the human stomach and induces various gastric lesions, ranging from gastritis to cancer. It is well recognized that host factors, especially genetic heterogeneity, may be important in gastric carcinogenesis interacting with H. pylori infection. Innate immunity plays a crucial role in host protection against pathogens, relying on pattern recognition receptors, such as the toll-like receptors (TLRs), to alter the immune system response to existing or invading bacteria. H. pylori lipopolysaccharide (LPS) is considered to be one of the virulence factors involved in the gastritis, inducing secretion of proinflammatory cytokines, inducible NO and oxygen radicals by activating monocytes and gastric epithelial cells. TLR4, a member of the TLR family and the main receptor of LPS[2,3], is involved in recognition of H. pylori and plays an important role in gastroduodenal diseases and gastric carcinogenesis[3,4]

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Results

Conclusion