FHIT and cancer: The fragile histidine triad (FHIT) gene is one of the earliest and most frequently altered genes in most human cancers.[56] Recent reports have reconfirmed FHIT as a tumor suppressor gene with roles in apoptosis and prevention of epithelial-mesenchymal transition, which FHIT leads to nucleotide imbalance, spontaneous replication stress, and DNA breaks.[56] The loss of FHIT expression induced by heavy smoking and alcohol consumption occurred during esophageal precancerous lesions and early cancer stage.[57]