Carcinogenesis of nasopharyngeal carcinoma: an alternate hypothetical mechanism.
Carcinogenesis of nasopharyngeal carcinoma: an alternate hypothetical mechanism.
复制标题
鼻咽癌的致癌作用：一种替代假设机制。
DOI：
10.1186/s40880-015-0068-9
复制
发表时间：
2016-01-06
影响因子：
--
通讯作者：
Wee JT
中科院分区：
文献类型：
--
作者：
Poh SS;Chua ML;Wee JT
目前提出的机制涉及早期和潜伏的EB病毒(EBV)感染在致癌级联反应中，而流行病学研究总是将鼻咽癌(NPC)与儿童早期EBV感染和慢性耳、鼻和鼻窦疾病联系在一起。此外，大多数鼻咽癌患者都存在EBV衣壳抗原的IgA抗体滴度(VCA-IgA)，这可以比实际的肿瘤表现早几年。如果儿童早期EBV感染确实是鼻咽癌发生的关键事件，人们将不得不解释为什么在EBV感染的高风险患者的正常鼻咽上皮中无法检测到病毒。也许在潜伏期，EBV驻留在唾液腺内，而不是上皮内。东亚表型具有对鼻咽癌易感性增加和唾液腺形态发生不成熟的特征，后者受到唾液腺形态发生与人类外胚浆蛋白受体基因(EDAR)的进化变异EDARV370A的关联影响，间接支持了这一说法。未成熟的唾液腺是否代表更有利于EBV的病灶尚不确定，但在传染性单核细胞增多症患者中，EBV已在这个解剖器官中分离出来。EB病毒诱导的唾液腺和肺部淋巴上皮瘤的存在进一步说明了病毒在粘膜下传播的可能性。此外，罗森·米勒的颅窝包含一个仅在生命的第一个十年活跃的变革区，人们可能会忍不住猜测，鼻咽癌可能会出现另一种致癌级联，这可能与人类乳头瘤病毒和宫颈癌的模型相似。
Current proposed mechanisms implicate both early and latent Epstein–Barr virus (EBV) infection in the carcinogenic cascade, whereas epidemiological studies have always associated nasopharyngeal carcinoma (NPC) with early childhood EBV infection and with chronic ear, nose, and sinus conditions. Moreover, most patients with NPC present with IgA antibody titers to EBV capsid antigen (VCA-IgA), which can precede actual tumor presentation by several years. If early childhood EBV infection indeed constitutes a key event in NPC carcinogenesis, one would have to explain the inability to detect the virus in normal nasopharyngeal epithelium of patients at a high risk for EBV infection. It is perhaps possible that EBV resides within the salivary glands, instead of the epithelium, during latency. This claim is indirectly supported by observations that the East Asian phenotype shares the characteristics of an increased susceptibility to NPC and immature salivary gland morphogenesis, the latter of which is influenced by the association of salivary gland morphogenesis with an evolutionary variant of the human ectodysplasin receptor gene (EDAR), EDARV370A. Whether the immature salivary gland represents a more favorable nidus for EBV is uncertain, but in patients with infectious mononucleosis, EBV has been isolated in this anatomical organ. The presence of EBV-induced lymphoepitheliomas in the salivary glands and lungs further addresses the possibility of submucosal spread of the virus. Adding to the fact that the fossa of Rosen Müller contains a transformative zone active only in the first decade of life, one might be tempted to speculate the possibility of an alternative carcinogenic cascade for NPC that is perhaps not dissimilar to the model of human papillomavirus and cervical cancer.