Alcohol consumption and cigarette smoke are risk factors for esophageal cancer, especially for multicentric carcinogenesis.

酒精代谢：脆性组氨酸三联体（FHIT）表达的缺失不仅与乙醇诱导的食管癌发生有关，而且与乙醇代谢途径中的多中心癌发生有关。乙醛脱氢酶2（ALDH 2）是乙醛解毒的主要酶，在食管癌和肺癌的发生中起重要作用。ALDH 2的非活性和活性形式在食管中被大量饮酒诱导，并且也支持ALDH 2缺乏可能是具有大量饮酒习惯的个体的食管癌的高风险因素的假设。Cyp 2 e1在Aldh 2基因敲除小鼠肝脏中的表达水平增加。因此，Aldh 2基因敲除小鼠可能是有用的模型动物，为酒精代谢和相关疾病的调查。吸烟：p16甲基化更频繁地观察到谁是重度吸烟者和鳞状细胞癌，比从不/轻吸烟者和腺癌，分别。表皮生长因子受体（EGFR）基因的突变在吸烟p20包-年的患者和在诊断肺癌前至少20年戒烟的患者中更常见。K-ras基因突变在吸烟者中的发生率高于不吸烟者，在高剂量吸烟者中的发生率高于低剂量吸烟者，提示EGFR和K-ras基因突变可能与吸烟暴露密切相关。

Alcohol metabolism: A loss of fragile histidine triad (FHIT) expression is associated not only with alcohol-induced esophageal carcinogenesis, but also with multicentric carcinogenesis, in the metabolic pathway of ethanol. Aldehyde dehydrogenase 2 (ALDH2) is a major enzyme for detoxification of acetaldehyde, and it is important for esophageal and ling carcinogenesis. Both inactive and active forms of ALDH2 are induced in the esophagus by heavy drinking and also support a hypothesis that ALDH2 deficiency might be a high-risk factor of esophageal cancer for the individuals having a heavy-drinking habit. The expression level of Cyp2e1 was increased in the liver from Aldh2-null mice. Therefore, Aldh2-null mice may be useful model animals for the investigation of alcohol metabolism and related diseases.Tobacco smoking: The methylation of p16 was more frequently observed in patients who were heavy smoker and with squamous cell carcinoma and than in never/ light smokers and adenocarinoma, respectively. The mutations in the epidermal growth factor receptor (EGFR) gene were more frequently observed in patients who smoked p20 pack-year, and in patients who quit at least 20 years before the date of diagnosis for lung cancer. The K-ras mutations were more frequently found in smokers than in never smokers, and in high-dose smokers than in low-dose smokers, suggesting that mutations of EGFR and k-ras might be strongly associated with exposure of tobacco smoking.