NFKB1 and bile reflux: Although the importance of the pH in the development and promotion of malignancies of the upper aerodigestive tract remains unclear [62,63], recent studies document that similar to strongly acidic pH, less acidic pH can cause bile-reflux-related malignant transformation of hypopharyngeal epithelial cells and activation of NF-κB and its anti-apoptotic molecular phenotype [64,65,66].