Lecture 13 Development of Colorectal Cancer How Common is Colon Cancer 3rd most common cancer 2nd most common cause of cancer death 1 in 18 will be affected Most common malignancy in GI Tract Your Gut Large intestine filters out water from waste Large intestine and small intestine Lymph nodes line the outside of the colon Over Age 50 Colorectal cancer is more likely to occur as people get older More than 90 of people with this disease are diagnosed after age 50 The average age at diagnosis is 72 Overview of Carcinogenesis Radiation chemicals infectious agents heredity oncogenes and inactivated of genetic and epigenetic changes can go back and cause additional mutations Accumulation of genetic and epigenetic changes Hallmarks of Cancer 1 Self sufficiency in growth signals 2 Insensitivity to antigrowth signals 3 Evasion of apoptosis 4 Limitless replicative potential 5 Sustained angiogenesis 6 Tissue invasion and metastasis Colorectal Cancer Most common sites colon cancer spreads to Directly through the colorectal wall into nearby tissues such as other parts of the colon next to the affected part or other organs that are very close to the affected part of the colon Through the lymphatic system to nearby lymph nodes Through the bloodstream to distant organs including liver lungs bones brain ovaries Normal tissue forms a polyp projecting from colon wall Over time polyp becomes tumor Stages Stage 0 Cancer has not grown beyond inner layer of colon wall Stage 1 Grown to outer layer of wall Stage 2 Tumor is through wall not spread to lymph nodes Stage 3 Spread to lymph nodes Stage 4 Cancer spreads to distant sites in body such as liver or lung The Colorectal Cancer Problem Colorectal cancer is the 2nd leading cause of cancer related deaths in the U S Cancer of the large intestine accounts for 21 of all cancers in the U S Estimated new cases and deaths from colon and rectal cancer in the U S in 2015 New cases 132 700 Deaths 49 700 Potentially one of the most curable of gastrointestinal cancers Geography Distribution of Sporadic Colon Cancer There is great variability in the worldwide incidence and mortality rates of colon cancer Industrialized nations appear to have the greatest risk while most developing nations have lower rates North America Western Europe Australia and New Zealand have high rates for colorectal neoplasms Progression of Colon Cancer benign growths Begins with the development of polyps in the epithelium of the colon Polyps are As time passes the polyps may get bigger At some point nests of malignant cells may appear within the polyps If the polyp is not removed some of these malignant cells will escape from the primary tumor and metastasize throughout the body At least 2 Gene Mutations Involved 1 Deletion of a healthy copy of the APC tumor suppressor gene on chromosome 5 or p53 chromosome 17 2 A mutant proto oncogene often RAS Typical Sequence of Genetic Changes Underlying the Development of a Colorectal Carcinoma Normal epithelium early adenoma Intermediate adenoma Late adenoma Carcinoma Invasion and Metastasis Signs and Symptoms Change in bowel habits including diarrhea constipation Rectal bleeding or blood in stools Persistent abdominal pain Colorectal Cancer Risk Factors Age over 50 Colorectal polyps Family history of colorectal cancer Genetic alterations Personal history of cancer Ulcerative colitis or Crohn s disease Diet Cigarette smoking New Risk Factors for Colorectal Cancer Most people who develop colorectal cancer have no identifiable risk factors Polyps non cancerous growths that can become cancerous over time Most colon cancers develop from polyps Family History of colon or rectal cancers chronic colitis or colon polyps Unless it is treated an inherited condition called familial polyposis puts a person at very high risk Age Colon and rectal cancers occur most often in people over age 50 Having long term inflammation of the colon diseases called ulcerative colitis or Crohn s disease Eating a diet high in fat and low in fiber Physical inactivity Sporadic mutation not genetic colon cancer 50 60 Familial colon cancer 30 40 Non polyposis syndromes 3 5 Genetic polyposis 1 Screening Recommendations Beginning at the age of 50 years persons at average risk for colorectal cancer undergo one of the following screening regimens 1 Fecal occult blood testing annually 2 Flexible sigmoidoscopy every five years 3 Fecal occult blood testing annually plus flexible sigmoidoscopy every five years 4 Double contrast barium enema every five to ten years 5 Colonoscopy every 10 years Colonoscopy Colonoscopy is the most widely used diagnostic method to study the colon and has the highest diagnostic sensitivity and specificity of all available tests Ninety to 95 of the colon can be examined in most studies Test annually takes 60 minutes or less to complete and may be both diagnostic Offers the flexibility of performing biopsy of suspicious regions and the ability to The sensitivity of colonoscopy for the detection of polyps greater than or equal to and therapeutic perform endoscopic polypectomy 1cm and tumors is greater than 95 Colonoscopy is the preferred procedure for diagnosis of symptomatic patient and is the gold standard for the diagnosis of colorectal neoplasms Less Microbial Diversity in Guts with Colon Cancer Metagenomic analysis of faecal microbiome as a tool towards targeted non invasive biomarkers for colorectal cancer A study found that they could use 4 specific genes to predict who had cancer good accuracy Surgery Effective Treatment with Early Detection Surgical Removal of Polyps and Tumors Colectomy Stage 0 Stage 1 Stage 2 rarely with chemo and or radiation post sugery Stage 3 With chemo and or radiation post surgery Stage 4 Surgery unlikely to help chemotherapy and radiation American non hispanic black male population higher colorectal cancer incidence rates and mortality Aspirin Lowers Colorectal Cancer Rates Chromic aspirin users have lower colon cancer rates
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