Upper gastrointestinal (GI) cancers such as oral (OC), esophageal (EC), and gastric (GC) cancers affect the digestive system, with a high mortality rate. Clinical symptoms are, however, not recognizable at early stages, and most patients are diagnosed in advanced stages. Therefore, the mechanism underlying the origin and development of upper GI cancer must be evaluated and also new therapeutic targets and effective methods should be identified and established to control GI cancers. Genome-wide approaches have introduced many long non-coding RNAs (lncRNAs) transcribed in various manners in malignant and normal tissues. It is found that the aberrant expression of specific lncRNAs is closely associated with the diagnosis or prognosis of the patients with upper GI cancers and involved in targeted therapy, which may improve the development of prevention strategies and advanced therapies. lncRNA-associated SNPs show amazing variations in interfering with the lncRNA function of regulating genes which contribute to important signaling pathways and carcinogenesis. Most data on genetic variations in lncRNAs have considered polymorphisms in focal amplifications and regulatory regions, which influence the levels of expression rather than lncRNA functionalities. The present study attempted to summarize lncRNA-related polymorphisms effective in the development of upper GI cancers. It is proposed that the individual and combined genotypes of lncRNA-related polymorphisms may predict cancer risk, and in some cases the clinical and therapeutic outcomes.
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