Study of TLR4 and IL-8 Gene Polymorphisms in H.pylori-Induced Inflammation in Gastric Cancer in an Ethnic Kashmiri Population

Abstract

Background: TLRs play an essential role in the initial handling of H. pylori and determine the clinical outcomes that range from simple asymptomatic gastritis to peptic ulcer disease and gastric cancer. Asp299Gly and Thr399Ile polymorphisms in TLR4 have been associated with a variety of inflammatory and infectious conditions including gastric cancer. The T-251A polymorphism in the promoter region of IL-8 gene has been found to be associated with changing the in vitro levels of IL-8 production. IL-8 exhibits angiogenic activity and is responsible for tumor-associated angiogenesis in several cancers.

Materials and methods: 130 gastric cancer patients and 200 healthy controls were included in this study. DNA extraction was followed by PCR detection of H. pylori infection, PCR-RFLP for the TLR 4 polymorphism and PCR-CTPP for IL-8 gene polymorphism.

Results: The adjusted OR for gastric cancer risk was 1.15 (95% CI, 0.8357–1.3463); 1.39 (0.6964-2.781) and 1.43 (0.954–2.1515) for Asp299Gly, Thr399Ile and IL-8 T_251A respectively. Odds Ratio analysis showed CT genotype and AT and AA genotypes as risk factors for the development of gastric cancer. We found the Asp299Gly polymorphism carrier to be significantly associated (p value 0.03)with the development of tumours in the distal part of the stomach and Thr399Ile polymorphism to be significantly associated(p value 0.008) with the development of well-differentiated gastric adenocarcinoma.The IL-8 T-251A polymorphism was not found to be associated with any of the clinicopathological characteristics.

Discussion: No correlation was found between the appearance of disease and HP infection or the presence of TLR4 and IL-8 gene polymorphisms and HP infection.

• Gastric cancer
• H. pylori
• IL-8
• inflammation
• polymorphism
• Toll like receptors

Acknowledgement

The authors are highly indebted to the theatrical staff of the General Surgery department (SKIMS) and the technical staff of the Department of Gastroenterology (SKIMS) for making the sample collection possible.