Varela-Rey Marta, Woodhoo Ashwin, Martinez-Chantar Maria-Luz, Mato José M, Lu Shelly C
Centro de Investigación Cooperative en Biosciencias (CIC bioGUNE), Technology Park of Bizkaia, Derio, Spain.
Alcohol Res. 2013;35(1):25-35.
Cancer is one of the most significant diseases associated with chronic alcohol consumption, and chronic drinking is a strong risk factor for cancer, particularly of the upper aerodigestive tract, liver, colorectum, and breast. Several factors contribute to alcohol-induced cancer development (i.e., carcinogenesis), including the actions of acetaldehyde, the first and primary metabolite of ethanol, and oxidative stress. However, increasing evidence suggests that aberrant patterns of DNA methylation, an important epigenetic mechanism of transcriptional control, also could be part of the pathogenetic mechanisms that lead to alcohol-induced cancer development. The effects of alcohol on global and local DNA methylation patterns likely are mediated by its ability to interfere with the availability of the principal biological methyl donor, S-adenosylmethionine (SAMe), as well as pathways related to it. Several mechanisms may mediate the effects of alcohol on DNA methylation, including reduced folate levels and inhibition of key enzymes in one-carbon metabolism that ultimately lead to lower SAMe levels, as well as inhibition of activity and expression of enzymes involved in DNA methylation (i.e., DNA methyltransferases). Finally, variations (i.e., polymorphisms) of several genes involved in one-carbon metabolism also modulate the risk of alcohol-associated carcinogenesis.
癌症是与长期饮酒相关的最重要疾病之一，长期饮酒是患癌的一个重要风险因素，尤其是上消化道、肝脏、结肠直肠和乳腺的癌症。酒精诱导癌症发生（即致癌作用）有多种因素，包括乙醇的首要代谢产物乙醛的作用以及氧化应激。然而，越来越多的证据表明，DNA甲基化异常模式作为转录调控的一种重要表观遗传机制，也可能是导致酒精诱导癌症发生的发病机制的一部分。酒精对整体和局部DNA甲基化模式的影响可能是通过其干扰主要生物甲基供体S-腺苷甲硫氨酸（SAMe）及其相关途径的可用性来介导的。酒精对DNA甲基化的影响可能由多种机制介导，包括叶酸水平降低以及一碳代谢关键酶的抑制，最终导致SAMe水平降低，以及DNA甲基化相关酶（即DNA甲基转移酶）的活性和表达受到抑制。最后，参与一碳代谢的多个基因的变异（即多态性）也会调节酒精相关致癌作用的风险。
