Qadri Qurteeba, Rasool Roohi, Afroze Dil, Naqash Sameer, Gulzar G M, Yousuf Adfar, Siddiqi M A, Shah Zafar A
Department of Immunology and Molecular Medicine, Sher-i-Kashmir Institute of Medical Sciences (SKIMS) , Soura, Kashmir, Jammu and Kashmir .
Immunol Invest. 2014;43(4):324-36. doi: 10.3109/08820139.2013.854378. Epub 2013 Dec 2.
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.
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.
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.
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.
Toll样受体（TLRs）在幽门螺杆菌的初始处理中起重要作用，并决定临床结果，范围从单纯无症状性胃炎到消化性溃疡疾病和胃癌。TLR4中的Asp299Gly和Thr399Ile多态性与包括胃癌在内的多种炎症和感染性疾病有关。白细胞介素8（IL-8）基因启动子区域的T-251A多态性已被发现与改变体外IL-8产生水平有关。IL-8具有血管生成活性，并在几种癌症中负责肿瘤相关的血管生成。
本研究纳入130例胃癌患者和200例健康对照。提取DNA后，采用PCR检测幽门螺杆菌感染，PCR-RFLP检测TLR 4多态性，PCR-CTPP检测IL-8基因多态性。
胃癌风险的校正比值比（OR）分别为：Asp299Gly为1.15（95%可信区间，0.8357-1.3463）；Thr399Ile为1.39（0.6964-2.781）；IL-8 T_251A为1.43（0.954-2.1515）。优势比分析显示CT基因型以及AT和AA基因型是胃癌发生的危险因素。我们发现Asp299Gly多态性携带者与胃远端肿瘤的发生显著相关（p值为p值0.03），Thr399Ile多态性与高分化胃腺癌的发生显著相关（p值0.008）。未发现IL-8 T-251A多态性与任何临床病理特征相关。
未发现疾病的出现与幽门螺杆菌感染或TLR4和IL-8基因多态性的存在及幽门螺杆菌感染之间存在相关性。
