However, it is not certain whether these changes occur in early-stage predysplastic sporadic cases, as TOC individuals represent a unique ESCC-predisposition cohort, and RHBDF2 mutations are not known to be found in sporadic ESCCs unlike other familial cancer genes; rather, the genomic loci containing RHBDF2 is frequently deleted in ESCC.35 Here, RHBDF2 is linked to hereditary cancer.