Given literature’s contradictory results with Hong et al [49] suggesting that the HULC rs7763881 is associated with increased GC susceptibility and Elhelaly et al. [50]suggesting association with breast cancer in Egyptians, we conducted our case-control study to explore its role in EC/EAC/ESCC genetic footprint in western ethnicity. This evidence concerns the gene HULC and esophageal squamous cell carcinoma.