title: Molecular mechanisms of ethanol-associated oro-esophageal squamous cell carcinoma.
abstract: Alcohol drinking is a major etiological factor of oro-esophageal squamous cell carcinoma (OESCC). Both local and systemic effects of ethanol may promote carcinogenesis, especially among chronic alcoholics. However, molecular mechanisms of ethanol-associated OESCC are still not well understood. In this review, we summarize current understandings and propose three mechanisms of ethanol-associated OESCC: (1) Disturbance of systemic metabolism of nutrients: during ethanol metabolism in the liver, systemic metabolism of retinoids, zinc, iron and methyl groups is altered. These nutrients are known to be associated with the development of OESCC. (2) Disturbance of redox metabolism in squamous epithelial cells: when ethanol is metabolized in oro-esophageal squamous epithelial cells, reactive oxygen species are generated and produce oxidative damage. Meanwhile, ethanol may also disturb fatty-acid metabolism in these cells. (3) Disturbance of signaling pathways in squamous epithelial cells: due to its physico-chemical properties, ethanol changes cell membrane fluidity and shape, and may thus impact multiple signaling pathways. Advanced molecular techniques in genomics, epigenomics, metabolomics and microbiomics will help us elucidate how ethanol promotes OESCC.
authors.affiliation: Department of Oral Medicine, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China; Cancer Research Program, JLC-BBRI, North Carolina Central University, Durham, NC 27707, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Cancer Research Program, JLC-BBRI, North Carolina Central University, Durham, NC 27707, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Oral Medicine, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China. Electronic address: zhengsun12@vip.126.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Cancer Research Program, JLC-BBRI, North Carolina Central University, Durham, NC 27707, USA. Electronic address: lchen@nccu.edu.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Chen
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000209:etiology* / Q000378:metabolism; D000077277:Esophageal Squamous Cell Carcinoma; D000431:Ethanol / Q000506:poisoning*; D006801:Humans; D015398:Signal Transduction
chemical_list: D000431:Ethanol
keywords: Ethanol; Molecular mechanisms; Oro-esophageal squamous cell carcinoma