Recent data have provided direct evidence that the mucosa of the upper aerodigestive tract under chronic exposure to tobacco smoke components with or without the combination of gastroduodenal refluxate can induce premalignant lesions and deregulated DNA repair mechanisms, leading to invasive cancer through the activation of cancer-related inflammatory molecules, such as NF-kB and related oncogenic pathways [21,22,23]. The gene discussed is NFKB1; the disease is cancer.