Hoes Lore, Dok Rüveyda, Verstrepen Kevin J, Nuyts Sandra
Laboratory for Systems Biology, VIB-KU Leuven Center for Microbiology, 3000 Leuven, Belgium.
Laboratory of Genetics and Genomics, Centre for Microbial and Plant Genetics, KU Leuven, 3000 Leuven, Belgium.
Cancers (Basel). 2021 Jul 30;13(15):3846. doi: 10.3390/cancers13153846.
Alcohol consumption is an underestimated risk factor for the development of precancerous lesions in the oral cavity. Although alcohol is a well-accepted recreational drug, 26.4% of all lip and oral cavity cancers worldwide are related to heavy drinking. Molecular mechanisms underlying this carcinogenic effect of ethanol are still under investigation. An important damaging effect comes from the first metabolite of ethanol, being acetaldehyde. Concentrations of acetaldehyde detected in the oral cavity are relatively high due to the metabolization of ethanol by oral microbes. Acetaldehyde can directly damage the DNA by the formation of mutagenic DNA adducts and interstrand crosslinks. Additionally, ethanol is known to affect epigenetic methylation and acetylation patterns, which are important regulators of gene expression. Ethanol-induced hypomethylation can activate the expression of oncogenes which subsequently can result in malignant transformation. The recent identification of ethanol-related mutational signatures emphasizes the role of acetaldehyde in alcohol-associated carcinogenesis. However, not all signatures associated with alcohol intake also relate to acetaldehyde. This finding highlights that there might be other effects of ethanol yet to be discovered.
饮酒是口腔癌前病变发生的一个被低估的风险因素。尽管酒精是一种广为人知的消遣性药物，但全球所有唇癌和口腔癌中有26.4%与大量饮酒有关。乙醇这种致癌作用的分子机制仍在研究中。一个重要的破坏作用来自乙醇的第一种代谢产物乙醛。由于口腔微生物对乙醇的代谢作用，口腔中检测到的乙醛浓度相对较高。乙醛可通过形成诱变DNA加合物和链间交联直接损伤DNA。此外，已知乙醇会影响表观遗传甲基化和乙酰化模式，而这些是基因表达的重要调节因子。乙醇诱导的低甲基化可激活癌基因的表达，随后可能导致恶性转化。最近对乙醇相关突变特征的鉴定强调了乙醛在酒精相关致癌作用中的作用。然而，并非所有与饮酒相关的特征都与乙醛有关。这一发现凸显出乙醇可能还有其他尚未被发现的作用。
