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

酒精代谢：在乙醇的代谢途径中，脆性组氨酸三联体(FHIT)的表达缺失不仅与酒精诱导的食道癌有关，而且与多中心癌的发生有关。乙醛脱氢酶2(ALDH2)是乙醛解毒的主要酶，在食管癌的发生发展中起重要作用。ALDH2的非活性和活性形式都是由大量饮酒在食道中诱导的，也支持了这样的假设，即对于有大量饮酒习惯的人来说，ALDH2缺乏可能是食道癌的高危因素。ALDH2基因缺失组小鼠肝脏中细胞色素P4502基因的表达水平升高。因此，ALDH2缺失小鼠可能是研究酒精代谢和相关疾病的有用的模型动物。吸烟：p16甲基化分别在重度吸烟者和鳞状细胞癌患者中更常见，而在从不/轻度吸烟者和腺癌患者中则更常见。表皮生长因子受体(EGFR)基因的突变更多地出现在吸烟20年的患者中，以及在诊断为肺癌的日期至少20年前戒烟的患者。K-ras基因突变在吸烟者中比不吸烟者中更常见，在高剂量吸烟者中比在低剂量吸烟者中更常见，这表明EGFR和k-ras突变可能与吸烟密切相关。

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.