人类白细胞抗原A、B等位基因与潮汕人群鼻咽癌临床相关性及预后关系的研究

发布时间：2018-04-24 14:05

  本文选题：鼻咽癌 + 人类白细胞抗原　； 参考：《汕头大学》2011年硕士论文

【摘要】：背景 鼻咽癌(nasopharyngealcarcinoma,NPC)是起源于鼻咽上皮的恶性肿瘤,也是耳鼻咽喉科最常见的恶性肿瘤。NPC在西方国家十分罕见而在中国南方人群中发病率较高,呈现出明显的地区聚集性、家族聚集性和种族易感性。NPC的病因至今尚未完全明确,目前认为主要由EB病毒、环境因素和遗传因素等综合作用所致。人类白细胞抗原(humanleukocyteantigen,HLA)在NPC发病过程中起着重要作用,目前已有研究证实HLA-A02、-B46、A02-B46、A33-B58等为中国南方人群NPC发生的危险性因素,而HLA-A11、-A31、-B27等为NPC发生的保护性因素。我们课题组前期通过对247例潮汕地区NPC患者和274例潮汕正常人群进行研究也证实了在潮汕人群中HLA与NPC的相关性,并提示有NPC隐性基因存在于HLA区域内导致中国南方人群NPC的发生。但目前关于HLA在NPC临床进展中的作用还鲜有报道,在前期研究的基础上,本研究旨在探讨HLA与NPC临床进展及预后的相关性。 目的 分析HLA-A、-B等位基因与NPC临床特征的关系,并研究二者与NPC5年生存预后的关系。 材料与方法 回顾总结课题组前期HLA-NPC相关性研究中的NPC患者HLA-A、-B等位基因分型结果,并进一步收集其临床信息。本研究231例NPC患者均为潮汕籍,其中男性174例,女性57例,男女之比为3.1:1;平均年龄47.7岁(14～76岁)。HLA-A、-B等位基因与NPC患者临床特征的相关性采用二分类Logistic回归分析;用Kaplan-Meier方法进行生存估计,Log-rank分析组间差异,用Cox比例风险模型进行生存分析。 结果 231例NPC患者整体五年生存率为65.8%,截至末次随访时间的总生存率为59.7%。Cox生存分析显示,231例NPC患者中,对NPC五年生存率有显著影响的因素有:年龄(RR=1.027)、抽烟(RR=1.781)、临床分期(RR=2.558),以及T(RR=1.568)、N(RR=2.578)、M(RR=6.904)分期等。对临床Ⅲ～Ⅳ期(n=167)NPC患者而言,Cox多因素分析显示,HLA-A24等位基因对其预后有显著影响(相对风险率RR=1.825,95%CI=1.117-2.981,P=0.016);HLA-A24携带者(n=53)的五年生存率明显低于HLA-A24非携带者(n=114)(生存率分别为47.2%和65.8%, Log-rankP=0.029),提示HLA-A24为NPC的独立预后因素;但所有被分析因素对Ⅰ～Ⅱ期(n=64)患者的预后无明显影响。此外,二分类Logistic回归分析显示HLA-A、-B等位基因与NPC患者病理类型、淋巴结转移与否、远处转移与否和临床分期等临床特征无相关性。 结论 处于临床Ⅲ～Ⅳ期的NPC患者,HLA-A24携带者的预后较非携带者要差,临床检测HLA-A24对判断NPC患者的预后可能会有所帮助。年龄、抽烟、临床分期及T、N、M分期是影响NPC预后的重要因素。HLA-A、-B等位基因和NPC临床特征之间无显著性相关。
[Abstract]:Background Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from nasopharyngeal epithelium and the most common malignant tumor in the family Otolaryngology. NPC is rare in western countries and has a high incidence in southern China. The etiology of familial agglomeration and ethnic susceptibility. NPC is not completely clear. It is believed that Epstein-Barr virus (EBV), environmental factors and genetic factors are the main factors. Human leukocyte antigens (NPC) play an important role in the pathogenesis of NPC. At present, it has been confirmed that HLA-A02P46A02-B46-A33-B58 is the risk factor of NPC in southern Chinese population, while HLA-A11A31B27 is the protective factor of NPC. The previous study of 247 NPC patients and 274 normal Chaoshan people in Chaoshan area also confirmed the correlation between HLA and NPC in Chaoshan population. It is suggested that the presence of NPC recessive gene in the HLA region leads to the occurrence of NPC in southern China. However, there are few reports on the role of HLA in the clinical progress of NPC. On the basis of previous studies, the purpose of this study is to explore the correlation between HLA and clinical progress and prognosis of NPC. Purpose To analyze the relationship between HLA-AG-B allele and clinical features of NPC, and to study the relationship between HLA-AG-B allele and the survival and prognosis of NPC5. Materials and methods The results of allelic typing of HLA-An B alleles in patients with NPC were reviewed and summarized in the previous HLA-NPC correlation study of our research group, and further clinical information was collected. In this study, 231 patients with NPC were all of Chaoshan nationality, including 174 males and 57 females with a ratio of 3.1: 1.The average age of 47.7 years was 1476 years old and the correlation between HLA-AHA-B allele and clinical characteristics of NPC patients was analyzed by two-classification Logistic regression analysis. Kaplan-Meier method was used to estimate survival and Log-rank was used to analyze the differences between groups, and Cox proportional risk model was used to analyze survival. Result The overall 5-year survival rate of 231 patients with NPC was 65.8%. The overall survival rate at the end of the last follow-up period was 59.7%.Cox survival analysis. The factors that had significant influence on the 5-year survival rate of NPC patients were as follows: age of RRN 1.027, smoking of RRN 1.781, clinical stage RRV 2.558, and TRR1. 568 NRR 2.578RR6.904. Cox multivariate analysis showed that HLA-A24 alleles significantly affected the prognosis of patients with stage 鈪，

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