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Abstract Colorectal Cancer is the third most common cancer in men and the second in women. The incidence varies 10 folds all over the world. It is more common in males than in females. The majority of the highest incidence rates were observed in Europe, North America and Oceania. CRC is the fourth common cause of death in males and the third in females from cancers. The death rates have been declined progressively since the mid 1980s in the United States and in many other western countries. The improvement in outcome is attributed to detection and removal of colonic polyps, detection at earlier stages and more effective treatment. CRC genetics is one of the most studied and understandable cancer genetics. CRC can be presented in three different patterns according to genetics, sporadic, most of cases, due to stepwise accumulation of multiple somatic mutations, with no family history. The second pattern is inherited syndromes, due to germline mutation and can be divided to cancers with polyps and cancer without polyps. The last pattern is the familial CRC, in this category there is a strong family history but the genetics and presentations do not match with any known inherited syndrome. On the molecular level, there are at least three pathways that can lead to tumorigenesis. The first one is the chromosomal instability pathway, which may result from either activation of oncogenes or diminished activity of tumor suppressor genes. The other pathway is, the mutator phenotype/mismatch repair pathway, in which there is dysfunction of DNA mismatch repair genes, and formation of mircosatallite. Cancers that develops through this pathway have better prognosis and respond differently to standard chemotherapy. Hypermethylation phenotype pathway is another pathway through epigenetic alterations. There are many factors was found to increase the incidence of CRC like, family history of colon cancer, inherited syndromes, some medical conditions like ulcerative colitis and abdominal irradiation. There is a strong association between CRC and western lifestyle as high intake of red and processed meats, highly refined grain and starches and sugar is related to increase risk of CRC. Alcohol and cigarette are also considered to be risk factors for CRC. Observational studies have shown inverse associations between fruit and vegetable consumption, physical activity and CRC. It has been suggested that some therapeutic agents may play a prophylactic role in preventing the development of adenomas and cancers in the colon and rectum. These include aspirin, calcium, carotene, and antioxidants, notably vitamins A, C and E. There is an important role for surgery in prevention of colorectal cancer. The extent of colorectal resection depends on the location of the tumor, any underlying condition (eg, inflammatory bowel disease, hereditary syndrome), and the vascular supply to the colorectum. In familial adenomatous polyposis (FAP), prophylactic colectomy is generally indicated for all mutation carriers, usually at the end of the second to third decade. The role of prophylactic surgery in Lynch syndrome is less clear, but a subtotal colectomy is favored over a segmental resection when CRC is identified. For screening purposes, many tools have been used for early cancer detection. They differ from each other in sensitivity, specificity, complexity, effectiveness, complications and cost. Guaiac based fecal occult blood test is one of the oldest methods, there are different tests under that category but the most common one is “HemeOccult II test”. Fecal immunochemical test is a quantitative fecal occult blood test more specific than gFOBT and requires fewer stool samples. The newest fecal test is “Fecal DNA” which was designed to detect molecular abnormalities in cancer or precancerous lesions that are shed into the stool. FDA approved recently a new product for CRC screening (Cologuard) using that principle. Other important tools in CRC screening are the flexible sigmoidoscopy and colonoscopy. Colonoscopy is the gold standard examination tool for the colon and rectum as it is capable of both detection and removal of neoplasia. Imaging is used also in screening, double contrast barium enema used in the past but it is not common now due to the usage of newer tools. CT colonography is another imaging study but it has high specificity and sensitivity, the diagnostic ability for large adenomas is comparable with colonoscopy. The cost effectiveness of screening program should be considered. There is three measures of cost-effectiveness have been used: cost per cancer detected, cost per life saved and cost per life year saved There are multiple guidelines for CRC screening; most of them stratify guidelines according to the risk. They differ from each other in the recommended age, tools, frequency and alternatives. This review is emphasizing on the importance of colorectal cancer screening. As, it is the main cause in lowering the incidence and mortality of colorectal cancers in many countries. There are continuous changes in the tools and recommendations for colorectal cancers aiming to improve detection, compliance and survival. |