Department of Clinical Virology, University of Crete, School of Medicine, Heraklion, Crete - Greece.
Int J Biol Markers. 2012 Jan-Mar;27(1):1-12. doi: 10.5301/JBM.2011.8737.
Esophageal squamous-cell carcinoma (ESCC) is an invasive neoplastic disease generally associated with poor survival rates. The incidence of ESCC is characterized by marked geographic variation, with highest rates noted in developing Southeastern African, Central and Eastern Asian countries. In the developed Western European and North American regions where there is a low disease incidence, heavy alcohol and cigarette consumption constitute major risk factors. The toxic effects of both these risk factors cause chronic irritation and inflammation of the esophageal mucosa, while at the cellular level they further confer mutagenic effects by the activation of oncogenes (e.g., RAS mutations), inhibition of tumor-suppressor genes, and profound DNA damage. Viral infections, particularly with human papillomavirus, may activate specific antiapoptotic, proliferative and malignant cellular responses that may be intensified in combination with the effects of alcohol and tobacco. In countries with a high ESCC incidence, low socioeconomic status and an inadequate diet of poorly preserved food are combined with basic nutritional deficiencies and inadequate medical treatment. These conditions are favorable to the above-mentioned risk factors implicated in ESCC development, which may be present and/or habitually used in certain populations. New perspectives in epidemiological studies of ESCC development and its risk factors allow genome-wide research involving specific environments and habits. Such research should consist of adequately large and representative samples, should use newly designed informative genetic markers, and apply genomic variation analysis of the functional transcripts involved in malignant cell cycle regulation and neoplastic transformation in the multi-step process of ESCC carcinogenesis.
食管鳞状细胞癌（ESCC）是一种侵袭性的肿瘤疾病，通常与生存率低有关。ESCC 的发病率具有明显的地域差异，在发展中东南非、中亚和东亚国家发病率最高。在发病率较低的西欧和北美发达地区，大量饮酒和吸烟是主要的危险因素。这两个危险因素的毒性作用会导致食管黏膜的慢性刺激和炎症，而在细胞水平上，它们通过激活癌基因（如 RAS 突变）、抑制肿瘤抑制基因和严重的 DNA 损伤进一步产生致突变作用。病毒感染，特别是人乳头瘤病毒，可能会激活特定的抗凋亡、增殖和恶性细胞反应，这些反应可能会与酒精和烟草的作用结合而加剧。在 ESCC 发病率较高的国家，社会经济地位低、饮食中保存不当的食物不足，加上基本营养缺乏和医疗不足。这些情况有利于上述与 ESCC 发展相关的危险因素的存在和/或在某些人群中习惯性使用。ESCC 发展及其危险因素的流行病学研究的新观点允许涉及特定环境和习惯的全基因组研究。此类研究应包括足够大和有代表性的样本，应使用新设计的信息遗传标记，并应用涉及恶性细胞周期调控和肿瘤转化的功能转录本的基因组变异分析，以在 ESCC 癌变的多步骤过程中。
