HLA-DRB1^＊1501和DQB1^＊0602与新疆哈萨克族HPV感染及食管癌发生的相关性研究

Study of the Relationship Between HLA DRB1^＊1501, DQB1^＊0602 and Xinjiang Kazakh National Minority HPV Infection and Esophageal Carcinoma

目的：从基因水平探讨新疆哈萨克族食管鳞癌的HPV16E6感染及食管鳞癌发生与HLA—DRB1，DQB1等位基因的遗传易感性，为寻找哈萨克族食管鳞癌的易感基因提供参考。方法：采用聚合酶链反应（PCR）技术检测200例哈萨克族食管鳞癌和150例哈族萨克正常人群HPV16E6基因的表达情况，运用序列特异性引物聚合酶链反应技术（PCR—SSP），检测新疆哈萨克族食管鳞癌患者200例，哈萨克族正常人群食管膜膜150例的HLA—DRB1^＊1501和HLA—DQB1^＊0602的分布。结果：新疆哈萨克族食管鳞癌患者HPV16E6感染率为41％，明显高于哈萨克族正常人群感染率的14％（P〈0．001，OR=3．94）；HPV16E6感染与哈萨克族正常人群HLA—DRB1^＊1501，HLA—DQB1^＊0602的无相关性（P〉0．05）；新疆哈萨克族食管鳞癌患者HLA—DRB1^＊1501和HLA～DQB1^＊0602基因分布频率显著高于哈萨克族正常人群（0．455：0．232，P〈0．001，OR=2．78；0．69比0．554，P=0．006，OR=1．80）；HLA～DQB1^＊0602基因阳性率在中低分化鳞癌组中（68．8％）的分布高于高分化鳞癌组（31．2％），差异有统计学意义（P〈0．05）。结论：HPV16E6的感染可能是新疆哈萨克族食管癌发生的重要因素之一。HLA—DRB1^＊1501和HLA—DQB1^＊0602是哈萨克族食管鳞癌的易感基因，其中HLA—DQB1^＊0602与哈萨克族食管鳞癌的分化程度有关。

Objective： To explore the association between HPV16E6 infection, the polymorphisms of HLA-DRB1, DQB1 alleles and Kazakh esophageal squamous cell carcinomas in Xinjiang to further provide clues for Kazakh esophageal squamous cell carcinoma susceptibility genes. Methods： The HPV16E6 gene infection was detected by polymerase chain reaction （PCR） in 200 Kazakh patients with esophageal squamous cell carcinoma and 150 healthy controls . The polymorphisms of HLA-DRB1DRB1^＊1501 and HLA-DQB1^＊0602 were typed by sequence specific primer by using polymerase chain reaction （PCR-SSP） in 200 Kazakh patients with esophageal squamous cell carcinoma and 150 healthy controls. Results： Of the patients of Kazakhstan with esophageal squamous cell carcinoma, HPV16 E6 infection rate was 41%, significantly higher than that of ethnic Kazakh population whose infection rate was within the normal range of 14% （P〈 0.001, OR=3.94）; no correlation between the normal controls with Kazakhstan HPV16 E6 infection rate and HLA-DRB1^＊ 1501, DQB1^＊0602 was found （P〉0.05）. Allele frequencies of HLA-DRB1^＊1501 and HLA-DQB1^＊0602 of the patients from Kazakhstan with esophageal squamous cell carcinoma was higher than those in healthy controls （0.455 vs. 0.232, P〈 0.001, OR=2.78; 0.69 vs. 0.554, P=-0.006, OR=1.80, respectively）. HLA-DQB1^＊0602 gene-positive allele in poorly differentiated squamous cell carcinoma group （68.8 percent） was higher than that of well-differentiated squamous cell carcinoma group （31.2%）, the difference was statistically significant （P〈0.05）. Conclusion： HPV16 E6 infection may be an important factor causing squamous cell carcinoma in the Xinjiang Kazakhstan population. Individuals carrying HLA-DRB1^＊1501 and/or DQB1^＊0602 may be more susceptible to esophageal squamous cell carcinoma. HLA-DQB1^＊0602 is related to the differentiation of esophageal squamous cell carcinoma in the Kazakhstani participants.