Moreover, aberrant hypermethylation of the secreted frizzled-related protein 1 (SFRP1) promoter regions associated with reduced SFRP1 expression, which occurred in early EAC (Zou et al., 2005a), while altered methylation in Eyes absent homolog 4 (EYA4) promoter occurred in esophageal mucosa metaplasia and Barrett’s esophagus progression to EAC (Zou et al., 2005b) and hypermethylation of Runt-related transcription factor 3 (RUNX3) promoter was reported as an independent risk factor associated with Barrett’s esophagus-related EAC development (Schulmann et al., 2005). This evidence concerns the gene EYA4 and esophageal adenocarcinoma.