Abstract. Background: Patients with ulcerative colitis (UC)are at risk of UC-associated Colorectal carcinogenesis is considered to develop through multistep genetic or epigenetic alteration along with the pathological change called the adenoma-carcinoma sequence (1-5). Further accumulation of genetic changes confers invasiveness or metastatic potential on the tumor (6, 7), and to date, several indicators have been identified to predict outcomes (7,8). In contrast, colitic cancer, which develops through inflammation-prone carcinogenesis in patients with ulcerative colitis (UC), has a somewhat different etiology (9). UC is characterized by chronic inflammation of the colonic mucosa, and the underlying causes of inflammation are the disturbance or disorganization of the epithelial barrier, alteration of colonic microflora, and abnormal immune response caused by the dysregulation of the mucosal immune system (10). During the progression of colitis, genetic alterations associated with mucosal permeability [e.g. those in extracellular matrix protein 1 (ECM1), cadherin 1 (CDH1), and hepatocyte nuclear factor 4 alpha (HNF4A)] have been observed and considered to confer the risk of severe UC (11,12). The pathogenesis of colitic cancer originates from longstanding and severe bowel inflammation and differs from that of sporadic CRC in several aspects. For instance, colitic cancer often occurs multifocally and is widespread; therefore, performing total coloproctectomy is recommended if any dysplastic or cancerous lesions are identified in patients with UC. Moreover, the behavior and morphology of colitic cancer differ from those of sporadic CRC in that colitic cancer often invades to deeper layers of the bowel wall at an earlier stage of progression; this feature makes it difficult to identify dysplastic lesions when the tumor elevation and size is not large. These distinctive characteristics of colitic cancer are likely to be caused by its genetic etiology, which is different from that of sporadic cancer. However, to date, little information is available in this regard.In this study, we compared the mutation of oncogenes in colitic cancer to those in sporadic cancer. In addition, we examined the non-neoplastic mucosa of patients with colitic cancer, so as to identify the step in UC carcinogenesis in 341