Risk factors and molecular mechanisms of esophageal cancer: differences between the histologic subtypes

Abstract

The two major histologic subtypes of esophageal cancer have different risk factors as well as different molecular mechanisms. In this review, the differences in risk factors and genetic/epigenetic alterations between esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) will be discussed. Cigarette smoking and alcohol consumption are risk factors for ESCC, while gastroesophageal reflux, cigarette smoking, and obesity are the main EAC risk factors. Commonly mutated genes of both subtypes are TP53 and PIK3CA. Recent genome-wide analysis revealed that the activation of the RAC1 pathway may contribute to EAC tumorigenesis. Clustered abnormality in copy number was observed in several genes in ESCC, whereas a few genes were specifically altered at high frequency in EAC. Epigenetic changes, such as DNA methylation, histone modifications, and altered expression of microRNAs, have been revealed to influence carcinogenesis and progression of both ESCC and EAC.

Keywords

Epigenetic alterations / esophageal cancer / genetic alterations / risk factors

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