A third mechanism underlying biliary carcinogenesis in patients with PBM has been suggested to involve a chemically induced hyperplasia-dysplasia-carcinoma sequence secondary to reflux and stasis of bile mixed with pancreatic secretions in the bile duct and gallbladder with consequent gene mutations, particularly in K-ras and p53 [8,15,16,18,24,25]. The gene discussed is TP53; the disease is dysplasia.