文章：

酒精介导癌变的分子机制

Molecular mechanisms of alcohol-mediated carcinogenesis

原文发布日期：2007-08-01

DOI: 10.1038/nrc2191

类型: Review Article

开放获取: 否

要点：

1. Together with tobacco, alcohol is the most abundantly consumed noxious compound worldwide. Within the last decade, much knowledge about the pathophysiology of alcohol-related organ damage has been gathered that draws a much clearer picture of its potential dangers.
2. There is a clear association between chronic alcohol consumption and the development of cancers of the upper gastrointestinal tract, the liver, the colorectum and the female breast.
3. There is convincing evidence that acetaldehyde, the first metabolite produced during alcohol degradation, is responsible for the carcinogenic effect of ethanol on the upper aerodigestive tract owing to its multiple mutagenic effects on DNA.
4. Mechanisms of ethanol-induced hepatocarcinogenesis include the induction of cirrhosis of the liver, ethanol-related increase of oxidative stress, altered methylation and a reduction of retinoic acid.
5. An increase in oestradiols due to alcohol may contribute to breast cancer.
6. Patients with chronic hepatitis B and C; hereditary haemochromatosis and non-alcoholic fatty liver disease owing to insulin resistance; gastroesophageal reflux disease (GERD); and colorectal polyps are more susceptible to the carcinogenic properties of ethanol.
7. Carriers of the inactive aldehyde dehydrogenase 2^*2 (ALDH 2^*2) allele are at increased risk for alcohol-related oesophageal cancer. Carriers of other genetic variants, such as alcohol dehydrogenase 1C^*1 (ADH1C^*1) homozygotes and methylenetetrahydrofolate reductase (MTHFR) 677CT variants, should also be considered at higher risk for alcohol-related cancers.
8. Lifestyle factors such as smoking, poor oral hygiene, and certain dietary deficiencies (folate, vitamin B6, methyl donors) or an excess of others (vitamin A/β-carotene), owing to unevenly composed diets or self-medication, also increase the risk for alcohol-associated tumours.

要点翻译：

1. 酒精与烟草共同构成了全球范围内消耗最多的有害物质。过去十年间，关于酒精相关器官损伤的病理生理学研究取得了大量进展，更清晰地揭示了其潜在危害。
2. 长期饮酒与上消化道癌、肝癌、结直肠癌及女性乳腺癌的发生存在明确关联。
3. 有确凿证据表明，酒精降解过程中产生的首种代谢物乙醛，因其对DNA的多重诱变效应，是导致乙醇对上呼吸消化道产生致癌作用的主要原因。
4. 乙醇诱导肝癌发生的机制包括：诱发肝硬化、增加氧化应激、改变甲基化状态以及降低视黄酸水平。
5. 酒精引起的雌激素水平升高可能促进乳腺癌发展。
6. 慢性乙型/丙型肝炎患者、遗传性血色素沉着症患者、胰岛素抵抗导致的非酒精性脂肪肝患者、胃食管反流病患者以及结直肠息肉患者对乙醇的致癌作用更为敏感。
7. 携带失活醛脱氢酶2*2等位基因者发生酒精相关食管癌的风险显著增高。其他基因变异携带者，如酒精脱氢酶1C*1纯合子个体和亚甲基四氢叶酸还原酶677CT变异者，也应被视为酒精相关癌症的高危人群。
8. 吸烟、口腔卫生不良等生活方式因素，以及因膳食结构失衡或自行服药导致的特定营养素缺乏（叶酸、维生素B6、甲基供体）或过量（维生素A/β-胡萝卜素），也会增加酒精相关肿瘤的发生风险。

英文摘要：

Approximately 3.6% of cancers worldwide derive from chronic alcohol drinking, including those of the upper aerodigestive tract, the liver, the colorectum and the breast. Although the mechanisms for alcohol-associated carcinogenesis are not completely understood, most recent research has focused on acetaldehyde, the first and most toxic ethanol metabolite, as a cancer-causing agent. Ethanol may also stimulate carcinogenesis by inhibiting DNA methylation and by interacting with retinoid metabolism. Alcohol-related carcinogenesis may interact with other factors such as smoking, diet and comorbidities, and depends on genetic susceptibility.

摘要翻译： 

全球约3.6%的癌症源于长期饮酒，包括上呼吸消化道、肝脏、结直肠和乳腺的肿瘤。尽管酒精相关致癌机制尚未完全阐明，但最新研究多聚焦于乙醇的首个且毒性最强的代谢产物——乙醛，认为其是致癌因子。乙醇还可能通过抑制DNA甲基化及干扰视黄醇代谢促进癌变。酒精相关致癌过程可与吸烟、饮食及合并疾病等因素相互作用，并取决于遗传易感性。

原文链接：

Molecular mechanisms of alcohol-mediated carcinogenesis