Because HLA genes can harbor differential methylation profiles in Kazakh ESCC, and DNA methyltransferase inhibitors would likely reverse the hypomethylation status of both HLA-DRB1 and HLA-DQB1, it would be important to sub-group ESCC patients before adopting this kind of ‘precision’ epigenetic therapy. This evidence concerns the gene HLA-DRB1 and esophageal squamous cell carcinoma.