SMAD4 and cancer: In CCA associated with Opisthorchis viverrini (OS) infection, mutation of cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%), SMAD4 (16.7%), RNF43 (9.3%) and GNAS (9.3%) were reported and they may be involved in deactivation of histone modifiers, activation of G protein signaling and loss of genome stability [145].