云南哈尼族彝族幽门螺杆菌感染人群胃癌易感基因研究

胃癌的发生是生物、环境、宿主等因素共同作用的结果．宿主遗传因素与幽门螺杆菌（H．pylori）感染后的不同临床结局有关。目的：筛选云南红河州哈尼族彝族Hpylori感染人群的胃癌易感基因，探讨不同基因型和等位基因与H．pylori感染宿主胃癌发病风险的相关性。方法：通过PubMed、CNKI和HapMap数据筛选出12个中国人群胃癌易感相关单核苷酸多态性（SNP）位点，以芯片技术对哈尼族彝族H．pylori感染慢性胃炎和胃癌患者的这些SNP位点进行分型。结果：IL-1β-3IC／T和IL-1β-511C/T位点存在完全连锁不平衡．其基因型（P=0．014）和等位基因频率（P=0．049）在胃癌和胃炎组中有显著差异，-511CT／-31CT（OR=2．256，95％CI：1．048～4．855）和-511TT/-31CC（OR=3．312，95％CI：1．462～7．502）基因型胃癌发病风险显著高于-511CC／-31TT基因型。COX-2．899C／G位点基因型频率在胃癌和胃炎组中有显著差异（P=0．033），GG基因型胃癌发病风险显著高于CG基因型（OR=2．796，95％CI：1．053～7．423）。TNF—α-238A／G位点基因型频率在胃癌和胃炎组中有显著差异（P=0．037）．AA、AG基因型胃癌发病风险显著高于GG基因型（OR=2．600．95％CI：1．130～5．985）。结论：IL-1β-31C、IL-1β-511T等位基因和COX-2—899GG基因型可增高云南红河州哈尼族彝族Hpylori感染人群的胃癌发病风险，TNF-α-238GG基因型对上述人群的胃癌发生具有保护作用。

Study on Gastric Cancer Susceptibility Genes in Ethnic Hani and Yi Populations with Helicobacter pylori Infection in Yunnun Province

Background： Occurrence of gastric cancer is the result caused by biological, environmental and host factors, and the host genetic factors are correlated with the clinical outcomes of Helicobacter pylori （H. pylori） infection. Aims： To investigate the single uucleotide polymorphisms （SNP）, which were considered to increase the susceptibility to gastric cancer among the H. pylori-positive ethnic Hani and Yi populations in Honghe Region, Yunnan Province, and to study the correlation between divergent genotypes or alleles and gastric cancer risk of hosts with H. pylori infection. Methods： Twelve candidate SNPs susceptible to gastric cancer in Chinese population were screened by using PubMed and CNKI database and HapMap Project Data, and then H. pylori-positive ethnic Hani and Yi populations with chronic gastritis or gastric cancer were genotyped by microarray technology. Results： IL-1β-31C/T and IL-1β-511C/T loci were in complete linkage disequilibrium, and significant differences of the frequencies of their genotypes and alleles were found between gastric cancer group and gastritis group （P=0.014 and P=0.049, respectively）. The risk of gastric cancer in individuals with -511CT/-31CT （OR=2.256, 95% CI： 1.048-4.855） and-511TF/-31CC （OR=3.312, 95% CI： 1.462-7.502） genotypes were significantly higher than those with -511 CC/-31TT genotype. Genotype frequencies of COX-2 -899C/G and TNF-α-238MG loci showed significant differences between gastric cancer group and gastritis group （P=0.033 and P=0.037, respectively）.The risk of gastric cancer in individuals with GG genotype of COX-2 -899 locus was significantly higher than those with CG genotype （OR=2.796, 95% CI： 1.053-7.423）, while the groups with AA and AG genotypes of TNF-α-238 locus were more susceptible to gastric cancer when compared with those with GG genotype （OR=2.600, 95% CI： 1.130-5.985）. Conclusions： Allele IL-1β-31C, IL-1β-511T and genotype COX-2 -899GG increase the risk of gastric cancer among H. pylori-positive ethnic Hani and Yi populations in Honghe Region, Yunnan Province, whereas genotype TNF-α-238GG has protective effect against gastric cancer in the above populations.