Chen Che-Hong, Wang Wen-Lun, Hsu Ming-Hung, Mochly-Rosen Daria
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Internal Medicine, School of Medicine, College of Medicine, I-Shou University/E-Da Hospital, Kaohsiung 84001, Taiwan.
Life (Basel). 2022 Feb 27;12(3):348. doi: 10.3390/life12030348.
The upper aerodigestive tract (UADT) is highly susceptible to multiple primary cancers originated from squamous epithelia and constitutes a field of cancerization. Patients with head and neck cancer (head and neck squamous cell carcinoma, HNSCC) are at high risk of developing multiple cancers in the esophagus (esophageal squamous cell carcinoma, ESCC). Conversely, esophageal cancer patients are prone to develop multiple primary tumors in the head and neck region. The East Asian-specific dysfunctional missense mutation is a genetic risk factor for UADT cancer. It is not only associated with increased incidences of UADT cancer, but is also implicated in faster cancer progression and poorer prognosis. Alcohol use is a major lifestyle risk factor which causes UADT cancer among carriers. The accumulation of the immediate metabolite of alcohol, acetaldehyde, is likely the genotoxic agents that is involved in the process of tumorigenesis. This review summarizes recent publications on the risk and association of mutation, alcohol consumption in synchronous, metachronous UADT cancer. Possible molecular mechanisms involved in cancer initiation, progress and prognosis are discussed. The review also highlights a need for precision medicine-based preventive and therapeutic strategies by integrating lifestyle and genetic risk factors, such as alcohol consumption, genotypes of the alcohol metabolizing genes, and , into a risk assessment model for better screening, surveillance and treatment outcome.
上消化道呼吸道（UADT）极易发生源自鳞状上皮的多原发性癌症，并构成一个癌化区域。头颈部癌患者（头颈部鳞状细胞癌，HNSCC）发生食管癌（食管鳞状细胞癌，ESCC）的风险很高。相反，食管癌患者容易在头颈部区域发生多原发性肿瘤。东亚特有的功能失调错义突变是UADT癌症的一个遗传风险因素。它不仅与UADT癌症发病率增加有关，还与癌症进展更快和预后更差有关。饮酒是导致携带者发生UADT癌症的主要生活方式风险因素。酒精的直接代谢产物乙醛的积累可能是参与肿瘤发生过程的基因毒性剂。本综述总结了近期关于同步、异时性UADT癌症中突变、饮酒的风险及关联的出版物。讨论了癌症发生、进展和预后可能涉及的分子机制。该综述还强调需要通过将生活方式和遗传风险因素，如饮酒、酒精代谢基因的基因型以及[此处原文缺失相关内容]，整合到一个风险评估模型中，以实现基于精准医学预防和治疗策略，从而进行更好的筛查、监测和治疗效果评估。
