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鼻咽癌(NPC)是一种多因素复杂疾病。其发病过程涉及EB病毒慢性感染、环境致癌因素及宿主基因之间的相互作用。在这一过程中,那些宿主基因在EB病毒感染及鼻咽癌的发生发展中起了关键作用仍不清楚。本研究的目的是发现与鼻咽癌发生发展中两个关键步骤相关的遗传变异,即EB病毒持续性感染鼻咽部上皮细胞和鼻咽癌的形成。我们在广西梧州市及苍梧县鼻咽癌高发区收集汉族鼻咽癌患者350例、EB病毒壳抗原IgA抗体阳性者(IgA/VCA+)288例和EB病毒壳抗原IgA抗体阴性者(IgA/VCA-)346例。对先前鼻咽癌家系研究显示的鼻咽癌易感区4号染色体短臂(4p15.1~q12)进行了微卫星精细扫描,在18 Mb的范围内选择34个微卫星标记,包括319个等位基因,对其进行基因分型。比较分析NPC组和IgA/VCA+组等位基因频率结果显示,9个等位基因与鼻咽癌呈相关,其中5个为易感等位基因(OR=1.51~5.36,P=0.01~0.03),4个为限制性等位基因(OR值为0.3~0.71,P值为0.02~0.045)。比较分析IgA/VCA+组和IgA/VCA-组及比较所有IgA/VCA+者(包括NPC患者)和IgA/VCA-者等位基因频率的结果显示,12个等位基因与EB病毒壳抗原IgA抗体持续存在相关,其中3个在两组比较中均呈显著相关。等位基因D4S3241~136(P=0.004,OR=1.9,95%CI=1.2~3.0)和D4S3347-213(P=0.001,OR=1.6,95%CI=1.2~2.1)可增加EB病毒IgA/VCA抗体形成的危险,为易感基因;而等位基因D4S174-202(P=0.001,OR=0.5,95%CI=0.3~0.7)可限制IgA/VCA抗体的形成。但上述结果经多因素比较校正后,均失去相关性。结果不能确定该区域与非家族性鼻咽癌的形成相关,但本研究却提供了进一步发现鼻咽癌相关基因的研究模式。有关4号染色体短臂与EB病毒慢性持续感染及鼻咽癌的形成仍值得进一步深入研究。
Nasopharyngeal carcinoma (NPC) is a multifactorial, complex disease. Its pathogenesis involves the chronic infection of Epstein-Barr virus, environmental carcinogens and the interaction between host genes. In this process, those host genes play a key role in the development of Epstein-Barr virus infection and nasopharyngeal carcinoma, but it remains unclear. The purpose of this study was to discover the genetic variations associated with two key steps in the development of NPC, namely, the persistent infection of EB virus with the formation of nasopharyngeal epithelial cells and nasopharyngeal carcinoma. We collected 350 cases of Han patients with nasopharyngeal carcinoma, 288 cases of IgA / EBV positive IgA antibody (IgA / VCA +) and Epstein-Barr virus (IgA) negative IgA / IgA antibody in the high incidence areas of nasopharyngeal carcinoma in Wuzhou City and Cangwu County of Guangxi. VCA-) 346 cases. Microsatellite microscopy was performed on the short arm of chromosome 4 (4p15.1 ~ q12) in the susceptible region of nasopharyngeal carcinoma revealed by previous pedigrees of nasopharyngeal carcinoma and 34 microsatellite markers were selected in the range of 18 Mb, including 319 The alleles were genotyped. A comparative analysis of allele frequency between NPC and IgA / VCA + groups showed that 9 alleles were associated with NPC, of which 5 were susceptible alleles (OR = 1.51-5.36, P = 0.01-0.03) , 4 were restriction alleles (OR = 0.3-0.71, P = 0.02-0.045). A comparative analysis of the allele frequencies in IgA / VCA + and IgA / VCA- groups and in all IgA / VCA + patients (including NPC patients) and IgA / VCA- showed that 12 alleles were associated with Epstein-Barr virus envelope antigen IgA antibodies Persistent correlations, of which three were significantly correlated between the two groups. The allele D4S3241-136 (P = 0.004, OR = 1.9, 95% CI = 1.2-3.0) and D4S3347-213 (P = 0.001, OR = 1.6,95% CI = The risk of VCA antibody formation was a predisposing gene. However, the allele D4S174-202 (P = 0.001, OR = 0.5, 95% CI = 0.3-0.7) restricted the IgA / VCA antibody formation. However, after the above results were corrected by many factors, they all lost relevance. As a result, it is not confirmed that this region is associated with the development of non-familial nasopharyngeal carcinoma. However, this study provides a further study mode for the discovery of NPC-related genes. Chronic chromosome 4 short arm and Epstein-Barr virus chronic persistent infection and the formation of nasopharyngeal carcinoma is still worth further study.