title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Immunology and Molecular Medicine, Sher-i-Kashmir Institute of Medical Sciences (SKIMS) , Soura, Kashmir, Jammu and Kashmir .
authors.forename: Qurteeba
authors.initials: Q
authors.lastname: Qadri
authors.forename: Roohi
authors.initials: R
authors.lastname: Rasool
authors.forename: Dil
authors.initials: D
authors.lastname: Afroze
authors.forename: Sameer
authors.initials: S
authors.lastname: Naqash
authors.forename: G M
authors.initials: GM
authors.lastname: Gulzar
authors.forename: Adfar
authors.initials: A
authors.lastname: Yousuf
authors.forename: M A
authors.initials: MA
authors.lastname: Siddiqi
authors.forename: Zafar A
authors.initials: ZA
authors.lastname: Shah
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics*; D016480:Helicobacter pylori; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000209:etiology* / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D016209:Interleukin-8; D051197:Toll-Like Receptor 4