Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China.
Cancer Epidemiol Biomarkers Prev. 2011 Dec;20(12):2594-602. doi: 10.1158/1055-9965.EPI-11-0702. Epub 2011 Oct 12.
Genetic polymorphisms of Toll-like receptors (TLR) may influence the outcome of Helicobacter pylori infection and play important roles in gastric carcinogenesis. To screen the genetic variants of TLR2 and TLR5, and evaluate their associations with gastric cancer (GC) and its precursors, a population-based study was conducted in Linqu County, Shandong Province, China.
Genetic variants were identified by PCR-based denaturing high-performance liquid chromatography and PCR-restriction fragment length polymorphism analysis in 248 GC cases, 846 subjects with advanced gastric lesions including 350 dysplasia and 496 intestinal metaplasia, and 496 superficial gastritis/mild chronic atrophic gastritis controls.
Nine allelic variants each were detected within the promoter and exons of TLR2 and TLR5. Among those, TLR2 c. -196 to -174 del carriers (ins/del+del/del) showed a significantly decreased risk of GC (adjusted OR, 0.66; 95% CI: 0.48-0.90), whereas TLR5 rs5744174 C carriers (TC+CC) had an increased risk of GC (OR, 1.43; 95% CI: 1.03-1.97). Further analysis indicated an elevated risk of GC in subjects with the TLR5 rs5744174 TC+CC genotype and H. pylori infection (OR, 3.35; 95% CI: 2.13-5.26), and a significant interaction between rs5744174 and H. pylori infection was observed (OR, 2.15; 95% CI: 1.12-4.16).
These findings suggest that TLR2 c. -196 to -174 ins > del, TLR5 rs5744174 and interaction between rs5744174 and H. pylori infection were associated with the development of GC.
TLR2 and TLR5 polymorphisms may play important roles in the process of H. pylori-related gastric carcinogenesis.
Toll 样受体（TLR）的遗传多态性可能影响幽门螺杆菌感染的结果，并在胃癌发生中发挥重要作用。为了筛选 TLR2 和 TLR5 的遗传变异，并评估其与胃癌（GC）及其前体的关系，在中国山东省临朐县进行了一项基于人群的研究。
通过基于 PCR 的变性高效液相色谱和 PCR-限制性片段长度多态性分析，在 248 例 GC 病例、846 例进展期胃病变患者（包括 350 例发育不良和 496 例肠化生）和 496 例浅表性胃炎/轻度慢性萎缩性胃炎对照中鉴定遗传变异。
在 TLR2 和 TLR5 的启动子和外显子中各检测到 9 种等位基因变异。其中，TLR2 c.-196 至-174del 携带者（ins/del+del/del）GC 的风险显著降低（调整后的 OR，0.66；95%CI：0.48-0.90），而 TLR5 rs5744174C 携带者（TC+CC）GC 的风险增加（OR，1.43；95%CI：1.03-1.97）。进一步分析表明，在携带 TLR5 rs5744174TC+CC 基因型和幽门螺杆菌感染的患者中，GC 的风险升高（OR，3.35；95%CI：2.13-5.26），并且观察到 rs5744174 与幽门螺杆菌感染之间存在显著的交互作用（OR，2.15；95%CI：1.12-4.16）。
这些发现表明 TLR2 c.-196 至-174ins>del、TLR5 rs5744174 以及 rs5744174 与幽门螺杆菌感染之间的相互作用与 GC 的发生有关。
TLR2 和 TLR5 多态性可能在幽门螺杆菌相关胃癌发生过程中发挥重要作用。
