cancer) in this colon segment. the diagram indicates sub-clones and sub-sub-clones that were precursors to the tumors. the term "field cancerization" was first used in 1953 to describe an area or "field" of epithelium that has been preconditioned (by what were largely unknown processes at the time) to predispose it towards development of cancer. since then, the terms "field cancerization", "field carcinogenesis", "field defect", and "field effect" have been used to describe pre-malignant or pre-neoplastic tissue in which new cancers are likely to arise. field defects are important in progression to colon cancer. however, as pointed out by rubin, "the vast majority of studies in cancer research has been done on well-defined tumors in vivo, or on discrete neoplastic foci in vitro. yet there is evidence that more than 80% of the somatic mutations found in mutator phenotype human colorectal tumors occur before the onset of terminal clonal expansion." similarly, vogelstein et al. pointed out that more than half of somatic mutations identified in tumors occurred in a pre-neoplastic phase (in a field defect), during growth of apparently normal cells. likewise, epigenetic alterations present in tumors may have occurred in pre-neoplastic field defects. an expanded view of field effect has been termed "etiologic field effect", which encompasses not only molecular and pathologic changes in pre-neoplastic cells but also influences of exogenous environmental factors and molecular changes in the local microenvironment on neoplastic evolution from tumor initiation to death. epigenetics epigenetic alterations are much more frequent in colon cancer than genetic (mutational) alterations. as described by vogelstein et al., an average cancer of the colon has only 1 or 2 oncogene mutations and 1 to 5 tumor suppressor mutations (together designated "driver mutations"), with about 60 further "passenger" mutations. the oncogenes and tumor suppressor genes are well studied and are described above under pathogenesis. in addition to epigenetic alteration of expression of mirnas, other common types of epigenetic alterations in cancers that change gene expression levels include direct hypermethylation or hypomethylation of cpg islands of protein-encoding genes and alterations in histones and chromosomal architecture that influence gene expression. as an example, 147 hypermethylations and 27 hypomethylations of protein coding genes were frequently associated with colorectal cancers. of the hypermethylated genes, 10 were hypermethylated in 100% of colon cancers, and many others were hypermethylated in more than 50% of colon cancers. in addition, 11 hypermethylations and 96 hypomethylations of mirnas were also associated with colorectal cancers. abnormal (aberrant) methylation occurs as a normal consequence of normal aging and the risk of colorectal cancer increases as a person gets older. the source and trigger of this age-related methylation is unknown. approximately half of the genes that show age-related methylation changes are the same genes that have been identified to be involved in the development of colorectal cancer. these findings may suggest a reason for age being associated with the increased risk of developing colorectal cancer. epigenetic reductions of dna repair enzyme expression may likely lead to the genomic and epigenomic instability characteristic of cancer. as summarized in the articles carcinogenesis and neoplasm, for sporadic cancers in general, a deficiency in dna repair is occasionally due to a mutation in a dna repair gene, but is much more frequently due to epigenetic alterations that reduce or silence expression of dna repair genes. epigenetic alterations involved in the development of colorectal cancer may affect a person's response to chemotherapy. genomics | epigenomics consensus molecular subtypes (cms) classification of colorectal cancer was first introduced in 2015. cms classification so far has been considered the most robust classification system available for crc that has a clear biological interpretability and the basis for future clinical stratification and subtype-based targeted interventions. a novel epigenome-based classification (epic) of colorectal cancer was proposed in 2021 introducing 4 enhancer subtypes in people with crc. chromatin states using 6 histone marks are characterized to identify epic subtypes. a combinatorial therapeutic approach based on the previously introduced consensus molecular subtypes (cmss) and epics could significantly enhance current treatment strategies. diagnosis colon cancer with extensive metastases to the liver colorectal cancer diagnosis is performed by sampling of areas of the colon suspicious for possible tumor development, typically during colonoscopy or sigmoidoscopy, depending on the location of the lesion. it is confirmed by microscopical examination of a tissue sample. medical imaging a colorectal cancer is sometimes initially discovered on ct scan. presence of metastases is determined by a ct scan of the chest, abdomen and pelvis. other potential imaging tests such as pet and mri may be used in certain cases. the latter is often used for rectal lesions to determine its local stage and to facilitate preoperative planning. histopathology relative incidence of various histopathological types of colorectal cancer. the vast majority of colorectal cancers are adenocarcinomas. micrograph of colorectal adenocarcinoma, showing "dirty necrosis". the histopathologic characteristics of the tumor are reported from the analysis of tissue taken from a biopsy or surgery. a pathology report contains a description of the microscopical characteristics of the tumor tissue, including both tumor cells and how the tumor invades into healthy tissues and finally if the tumor appears to be completely removed. the most common form of colon cancer is adenocarcinoma, constituting between 95% and 98% of all cases of colorectal cancer. other, rarer types include lymphoma, adenosquamous and squamous cell carcinoma. some subtypes are more aggressive. immunohistochemistry may be used in uncertain cases. staging main article: colon cancer staging staging of the cancer is based on both radiological and pathological findings. as with most other forms of cancer, tumor staging is based on the tnm system which considers how much the initial tumor has spread and the presence of metastases in lymph nodes and more distant organs. the ajcc 8th edition was published in 2018. prevention it has been estimated that about half of colorectal cancer cases are due to lifestyle factors, and about a quarter of all cases are preventable. increasing surveillance, engaging in physical activity, consuming a diet high in fiber, and reducing smoking and alcohol consumption decrease the risk. lifestyle lifestyle risk factors with strong evidence include lack of exercise, cigarette smoking, alcohol, and obesity. the risk of colon cancer can be reduced by maintaining a normal body weight through a combination of sufficient exercise and eating a healthy diet. current research consistently links eating more red meat and processed meat to a higher risk of the disease. starting in the 1970s, dietary recommendations to prevent colorectal cancer often included increasing the consumption of whole grains, fruits and vegetables, and reducing the intake of red meat and processed meats. this was based on animal studies and retrospective observational studies. however, large scale prospective studies have failed to demonstrate a significant protective effect, and due to the multiple causes of cancer and the complexity of studying correlations between diet and health, it is uncertain whether any specific dietary interventions will have significant protective effects.: 432–433 : 125–126 in 2018 the national cancer institute stated that "there is no reliable evidence that a diet started in adulthood that is low in fat and meat and high in fiber, fruits, and vegetables reduces the risk of crc by a clinically important degree." according to the world cancer research fund, consuming alcohol drinks and consuming processed meat both increase the risk of colorectal cancer. the 2014 world health organization cancer report noted that it has been hypothesized that dietary fiber might help prevent colorectal cancer, but most studies have not borne this out, and status of the science remained unclear as of 2014. a 2019 review, however, found evidence of benefit from dietary fiber and whole grains. the world cancer research fund listed the benefit of fiber for prevention of colorectal cancer as "probable" as of 2017. a 2022 umbrella review says there is "convincing evidence" for that association. higher physical activity is recommended. physical exercise is associated with a modest reduction in colon but not rectal cancer risk. high levels of physical activity reduce the risk of colon cancer by about 21%. sitting regularly for prolonged periods is associated with higher mortality from colon cancer. regular exercise does not negate the risk but does lower it. medication and supplements aspirin and celecoxib appear to decrease the risk of colorectal cancer in those at high risk. aspirin is recommended in those who are 50 to 60 years old, do not have an increased risk of bleeding, and are at risk for cardiovascular disease to prevent colorectal cancer. it is not recommended in those at average risk. there is tentative evidence for calcium supplementation, but it is not sufficient to make a recommendation. vitamin d intake and blood levels are associated with a lower risk of colon cancer. screening as more than 80% of colorectal cancers arise from adenomatous polyps, screening for this cancer is effective for both early detection and for prevention. diagnosis of cases of colorectal cancer through screening tends to occur 2–3 years before diagnosis of cases with symptoms. any polyps that are detected can be removed, usually by colonoscopy or sigmoidoscopy, and thus prevent them from turning into cancer. screening has the potential to reduce colorectal cancer deaths by 60%. the three main screening tests are colonoscopy, fecal occult blood testing, and flexible sigmoidoscopy. of the three, only sigmoidoscopy cannot screen the right side of the colon where 42% of cancers are found. flexible sigmoidoscopy, however, has the best evidence for decreasing the risk of death from any cause. fecal occult blood testing (fobt) of the stool is typically recommended every two years and can be either guaiac-based or immunochemical. if abnormal fobt results are found, participants are typically referred for a follow-up colonoscopy examination. when done once every 1–2 years, fobt screening reduces colorectal cancer deaths by 16% and among those participating in screening, colorectal cancer deaths can be reduced up to 23%, although it has not been proven to reduce all-cause mortality. immunochemical tests are accurate and do not require dietary or medication changes before testing. however, research in the uk has found that for these immunochemical tests, the threshold for further investigation is set at a point that may miss more than half of bowel cancer cases. the research suggests that the nhs england's bowel cancer screening programme could make better use of the test's ability to provide the exact concentration of blood in faeces (rather than only whether it is above or below a cutoff level). other options include virtual colonoscopy and stool dna screening testing (fit-dna). virtual colonoscopy via a ct scan appears as good as standard colonoscopy for detecting cancers and large adenomas but is expensive, associated with radiation exposure, and cannot remove any detected abnormal growths as standard colonoscopy can. stool dna screening test looks for biomarkers associated with colorectal cancer and precancerous lesions, including altered dna and blood hemoglobin. a positive result should be followed by colonoscopy. fit-dna has more false positives than fit and thus results in more adverse effects. further study is required as of 2016 to determine whether a three-year screening interval is correct. recommendations in the united states, screening is typically recommended between ages 50 and 75 years. the american cancer society recommends starting at the age of 45. for those between 76 and 85 years old, the decision to screen should be individualized. for those at high risk, screenings usually begin at around 40. several screening methods are recommended including stool-based tests every 2 years, sigmoidoscopy every 10 years with fecal immunochemical testing every two years, and colonoscopy every 10 years. it is unclear which of these two methods is better. colonoscopy may find more cancers in the first part of the colon, but is associated with greater cost and more complications. for people with average risk who have had a high-quality colonoscopy with normal results, the american gastroenterological association does not recommend any type of screening in the 10 years following the colonoscopy. for people over 75 or those with a life expectancy of less than 10 years, screening is not recommended. it takes about 10 years after screening for one out of a 1000 people to benefit. the uspstf list seven potential strategies for screening, with the most important thing being that at least one of these strategies is appropriately used. in canada, among those 50 to 75 years