Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan.
Int J Clin Oncol. 2010 Apr;15(2):135-44. doi: 10.1007/s10147-010-0057-6. Epub 2010 Mar 12.
Esophageal cancer is the eighth most common incident cancer in the world and ranks sixth among all cancers in mortality. Esophageal cancers are classified into two histological types; esophageal squamous cell carcinoma (ESCC), and adenocarcinoma, and the incidences of these types show a striking variety of geographic distribution, possibly reflecting differences in exposure to specific environmental factors. Both alcohol consumption and cigarette smoking are major risk factors for the development of ESCC. Acetaldehyde is the most toxic ethanol metabolite in alcohol-associated carcinogenesis, while ethanol itself stimulates carcinogenesis by inhibiting DNA methylation and by interacting with retinoid metabolism. Cigarette smoke contains more than 60 carcinogens and there are strong links between some of these carcinogens and various smoking-induced cancers; these mechanisms are well established. Synergistic effects of cigarette smoking and alcohol consumption are also observed in carcinogenesis of the upper aerodigestive tract. Of note, intensive molecular biological studies have revealed the molecular mechanisms involved in the development of ESCC, including genetic and epigenetic alterations. However, a wide range of molecular changes is associated with ESCC, possibly because the esophagus is exposed to many kinds of carcinogens including alcohol and cigarette smoke, and it remains unclear which alterations are the most critical for esophageal carcinogenesis. This brief review summarizes the general mechanisms of alcohol- and smoking-induced carcinogenesis and then discusses the mechanisms of the development of ESCC, with special attention to alcohol consumption and cigarette smoking.
食管癌是全球第八大常见癌症，也是癌症死亡率第六高的癌症。食管癌可分为两种组织学类型：食管鳞状细胞癌（ESCC）和腺癌，这两种类型的发病率分布存在显著差异，这可能反映了对特定环境因素的暴露差异。饮酒和吸烟是 ESCC 发展的主要危险因素。乙醛是与酒精相关致癌作用中最具毒性的乙醇代谢物，而乙醇本身通过抑制 DNA 甲基化和与类视黄醇代谢相互作用来刺激致癌作用。香烟烟雾中含有 60 多种致癌物质，其中一些致癌物质与某些吸烟引起的癌症之间存在强烈联系；这些机制已经得到充分证实。吸烟和饮酒在头颈部呼吸道癌的发生中也存在协同作用。值得注意的是，密集的分子生物学研究揭示了 ESCC 发展的分子机制，包括遗传和表观遗传改变。然而，与 ESCC 相关的分子变化范围很广，可能是因为食管暴露于多种致癌物质，包括酒精和香烟烟雾，目前尚不清楚哪些改变对食管癌变最重要。本综述总结了酒精和吸烟引起的致癌作用的一般机制，然后讨论了 ESCC 发展的机制，特别关注饮酒和吸烟。
