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COLORECTAL CANCER Colorectal Cancer arises in Epithelial cells outlining the lumen of Colon & Rectum. Epidemiology: Cancer is the 3rd cause of ww.(6,3 million D/Y). About 876,000 get CRC/Y. About 525 000 CRC, D/Y. Incidence Rate=15/ 100 000. CRC is the 3rd cancer killer after: 1 Lung Cancer > 2 Stomach. death COLORECTAL CANCER COLORECTAL POLYPS: Abnormal growths protruding into the large intestine. Common condition in 20% of adults. Most polyps are benign. They produce no symptoms. SYMPTOMS OF CRC: Rectal Bleeding. Change Of Bowel Habits. Abdominal Pain, Discomfort. Decreased Stool Diameter. Weight Loss. COLORECTAL CANCER How Are Polyps Diagnosed? Colorectal Endoscopy: 1. Colonoscopy. 2. Sigmoidoscopy. Barium enema x-ray techniq. Fecal Occult Blood Test. (FOBT) Removal of polyps is advised. Colostomy is performed for late stages. COLON CANCER As a result of accumulation of genetic alterations a polyp (adenoma) is formed which turns into a cancer. A progression from early to intermediate to late adenoma to a carcinoma. Staging System Characteristics 1: Degree of penetration in the bowel wall. 2: L.N. involvement. 3: Distant metastases. L.N. Involvement Liver Metastases Kidney Metastases STAGING SYSTEM OF C.C. Astler-Coller: A: Tumor limited to mucosa, B1: Tumor grows through muscularis mucosae, B2: Tumor grows beyond muscularis propria, C1: Stage B1 with regional L.N. metastases, C2: Stage B2 with regional L.N. metastases, D: Distant metastases. GRADING SYSTEM OF C.C. Grading: Normal cells (differentiated) Cancer (less differentiated). differentiation Faster growth & metastases. G1: Well differentiated, G2: Moderately well differentiated, G3: Poorly differentiated, G4: Undifferentiated. Less THE CELL CYCLE COLON CANCER P53 gene : (TSG) Located in the S.A. of chromosome 17. Code for phosphoprotein that functions as T.F. In respond to DNA damage P53 protein expression is increased, And regulates the transcription of genes that induce cell cycle arrest or apoptotic cell death. P53 mutation occurs in 80-90% of sporadic C.C. COLON CANCER Adenom. Polypopsi Coli (APC) gene: Located on L.A. of chromosome 5. APC protein plays a role in: regulation of apoptatic cell death; Transfection of normal APC gene into cell lines having 2 mutant APC genes induces apoptosis. Mutations on it occur on 50-80% of sporadic colonic adenoma. COLON CANCER H19 Gene: An imprinted & developmentally regulated gene. Its product remains untranslated (oncofetal mRNA). Expressed in tumors arising from tissues, which express it in the fetal life. Located on chromosome 11p15.5 To date, its function remains unknown.