Seitz Helmut K, Cho Chin Hin
Department of Medicine, Center of Alcohol Research, Liver Disease and Nutrition, Salem Medical Center, University of Heidelberg, Heidelberg, Germany.
Methods Mol Biol. 2009;472:217-41. doi: 10.1007/978-1-60327-492-0_9.
Tobacco smoke and alcohol are major risk factors for a variety of cancer sites, including those of the gastrointestinal tract. Tobacco smoke contains a great number of mutagenic and carcinogenic compounds, including polycyclic carbohydrates, nitrosamines, and nicotine, while ethanol per se has only weak carcinogenic potential, but its first metabolite, acetaldehyde, is a mutagen and carcinogen, since it forms stable adducts with DNA. The possibility of proto-oncogene mutation in gastrointestinal mucosa cells may be associated with tobacco smoking-induced cancers through the formation of unfavorable DNA adducts. Individuals with defective DNA repair mechanisms and unfavorable genetic make-up for carcinogen metabolism may be at increased risk for gastrointestinal cancers. Individuals with a high production rate of acetaldehyde from ethanol also have an increased cancer risk when they drink chronically. These include individuals with a genetically determined increased acetaldehyde production due to alcohol dehydrogenase polymorphism and those with a decreased detoxification of acetaldehyde due to acetaldehyde dehydrogenase mutation. In addition, oral bacterial overgrowth due to poor oral hygiene also increases salivary acetaldehyde. Dietary deficiencies such as a lack of folate, riboflavine, and zinc may also contribute to the increase cancer risk in the alcoholic patient. It is of considerable importance that smoking and drinking act synergistically. Smoking increases the acetaldehyde burden following alcohol consumption and drinking enhances the activation of various procarcinogens present in tobacco smoke due to increased metabolic activation by an induced cytochrome P450-2E1-dependent microsomal biotransformation system in the mucosa of the upper digestive tract and the liver.
烟草烟雾和酒精是包括胃肠道癌症在内的多种癌症的主要风险因素。烟草烟雾含有大量诱变和致癌化合物，包括多环碳水化合物、亚硝胺和尼古丁，而乙醇本身致癌潜力较弱，但其首个代谢产物乙醛是诱变剂和致癌物，因为它能与DNA形成稳定加合物。胃肠道黏膜细胞中原癌基因突变的可能性可能与吸烟导致的癌症有关，这是通过形成不利的DNA加合物实现的。DNA修复机制有缺陷以及致癌物代谢的基因组成不利的个体，患胃肠道癌症的风险可能会增加。乙醇乙醛生成率高的个体长期饮酒时患癌风险也会增加。这些个体包括因酒精脱氢酶多态性导致乙醛生成在基因上增加的个体，以及因乙醛脱氢酶突变导致乙醛解毒能力下降的个体。此外，口腔卫生差导致的口腔细菌过度生长也会增加唾液中的乙醛含量。饮食缺乏，如缺乏叶酸、核黄素和锌，也可能导致酒精性患者患癌风险增加。吸烟和饮酒协同作用非常重要。吸烟会增加饮酒后乙醛的负担，而饮酒会增强烟草烟雾中各种前致癌物的活化，这是由于上消化道和肝脏黏膜中诱导的细胞色素P450 - 2E1依赖性微粒体生物转化系统增加了代谢活化作用。
