Gastroenterology and Digestive Disorders

Biography

Biography: Deepak Ghuliani

Abstract

Colorectal Cancer (CRC), commonest gastrointestinal malignancy develops from the progression of acquired or hereditary premalignant lesions. 75% of colorectal cancers are “sporadic while a potential genetic influence is identified in the remaining 25% of patients. The tumor results from complex interactions between several risk factors (environ­mental, dietary, familial and hereditary) which become relevant during the different stages of colorectal carcinogenesis. The Chromosomal Instability (CIN)/Loss of Heterozygosity (LOH) pathway and the Microsatellite Instability (MIN)/Replication Error (RER) pathway are two well-described genetic pathways leading to the development of colorectal adenocarcinoma. Most, if not all colonic cancers develop from a precursor polyp. The most common neoplastic polyp with malignant potential is the adenoma .It follows the adenoma-carcinoma sequence where inactivation of APC gene sets the stage for accumulation of genetic damage leading to a malignancy. Carcinomas are found in 0% to 4% adenomas. Histologically divided as tubular, villous and tubulovillous- the size and histology of adenomas are independent risk factors. Serrated polyps - another type of neoplastic polyp are mixed hyperplastic and adenomatous polyps. The sessile and traditional serrated types are the definite precursors for colonic cancers. Adenomas, may occur sporadically or as part of one of the hereditary syndromes like Familial Adenomatous Polyposis (FAP), Attenuated FAP, Gardener’s and Turcot’s syndrome. FAP is the commonest adenomatous polyposis syndrome with 100 to 1000 polyps all over the colon, more in the left and associated with 1% of colonic cancers. Besides, several hamartomatous polyposis syndromes like Peutz-Jeghers syndrome and Juvenile polyposis syndrome have markedly increased risk of colonic cancer with development of extra-colonic manifestations, both malignant and non-malignant. Hereditary Non Polyposis Colonic Cancer (HNPCC) is the most common familial colorectal syndrome associated with 2-3% of colorectal cancers. The associated colonic cancer occurs at an early age (44 years), 70% are right sided with a 40% risk of synchronous and metachronous cancers. Other premalignant conditions include inflammatory bowel diseases: Ulcerative colitis and Crohn’s disease where the risk is directly proportional to extent and duration of disease. Thus early identification of these conditions not only provides the opportunity to either prevent the progression to cancer or diagnose cancer at an early curable stage but also allows for appropriate surveillance and management, which varies considerably between syndromes. Clinical testing for germline mutations should occur in the setting of appropriate genetic counseling and offer predictive testing for family members.