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Hereditary non-polyposis colon cancer
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∙ 13y ago
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Is colon cancer and uterus cancer related?
It could. There is a genetic condition called lynch syndrome or hereditary non-polyposis colon cancer (HNPCC) that could have colon cancer and other types of cancers, such as uterine, etc...
Is it possible for your child to get ovarian cancer if you have it?
Ovarian cancer is NOT contagious to the fetus directly. Meaning if you have ovarian cancer during pregnancy (which is extremely rare), these cancerous cells have no way of coming in contact with the developing fetus. All the cells from which your daughter will be derived will be from the single celled zygote formed from the union of egg and sperm. Ovarian cancers in children are extremely rare and are quite distinct from adult ovarian caners. The direct causes of ovarian cancer still remain unknown however. It is believed it has to do with the continual tissue-repair process that follows the monthly release of an egg through a tiny tear in an ovarian follicle (ovulation) throughout a woman's reproductive years. The formation and division of new cells at the rupture site may set up a situation in which genetic errors occur. Others propose that the increased hormone levels before and during ovulation may stimulate the growth of abnormal cells. The most significant risk factor for ovarian cancer is having an inherited mutation in one of two genes called breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2). These genes were originally identified in families with multiple cases of breast cancer but they're also responsible for about 5 percent to 10 percent of ovarian cancers. Another known genetic link involves an inherited syndrome called hereditary nonpolyposis colorectal cancer (HNPCC). Individuals in HNPCC families are at increased risk of cancers of the uterine lining (endometrium), colon, ovary, stomach and small intestine. Sometimes, ovarian cancer occurs in more than one family member but isn't the result of any known inherited gene alteration. Having a family history of ovarian cancer increases your risk of the disease, but not to the same degree as does having an inherited genetic defect. If you have one first-degree relative
Cancer can sometimes be an inheritable disease?
Yes, cancer can sometimes have a hereditary or genetic component. Some individuals may inherit gene mutations from their parents that increase their susceptibility to developing certain types of cancer. These inherited genetic mutations are associated with an increased risk of cancer, but they do not guarantee that cancer will develop. There are certain genes known as tumor suppressor genes and oncogenes that play crucial roles in regulating cell growth and preventing the formation of tumors. Mutations in these genes can lead to uncontrolled cell growth and an elevated risk of cancer. Two common types of hereditary cancer syndromes are: Hereditary Breast and Ovarian Cancer (HBOC): Mutations in the BRCA1 and BRCA2 genes are associated with an increased risk of breast and ovarian cancers. Individuals with these mutations have a higher-than-average risk of developing these cancers, as well as an increased risk of certain other cancers. Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer - HNPCC): This syndrome is caused by mutations in genes involved in DNA repair, such as MLH1, MSH2, MSH6, and PMS2. Lynch Syndrome is associated with an elevated risk of colorectal cancer and an increased risk of other cancers, including endometrial, ovarian, and stomach cancers. It's important to note that while hereditary factors can contribute to an increased risk of cancer, the majority of cancers are not directly inherited. Most cancers are believed to result from a combination of genetic, environmental, and lifestyle factors. If there is a family history of certain types of cancer, genetic counseling and testing may be recommended. Genetic testing can identify whether an individual carries specific mutations associated with an increased cancer risk. This information can help individuals and their healthcare providers make informed decisions about monitoring, prevention, and early detection strategies. If you have concerns about your risk of developing cancer based on your family history, it is advisable to discuss these concerns with a healthcare professional or a genetic counselor. They can provide guidance on genetic testing and help assess your individual risk factors.
Is colon cancer dominant or recessive?
Colon cancer is not classified as either dominant or recessive. Instead, it is considered a complex disease influenced by multiple factors, including genetic, environmental, and lifestyle factors. Genetic Factors: While some cases of colon cancer can be linked to specific genetic mutations that are inherited in a dominant or recessive pattern, many cases are due to a combination of genetic variations that increase the risk of developing the disease. For example, mutations in genes such as APC, MLH1, MSH2, MSH6, PMS2, and STK11 can increase the risk of hereditary colorectal cancer syndromes, such as familial adenomatous polyposis (FAP) or Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC). Environmental and Lifestyle Factors: Environmental factors such as diet, physical activity, smoking, alcohol consumption, and exposure to certain carcinogens can also significantly influence the risk of developing colon cancer. Lifestyle choices and environmental exposures can interact with genetic predispositions to increase or decrease the risk of developing the disease. Complex Inheritance: The inheritance pattern of colon cancer is complex and varies depending on the specific genetic mutations involved. Some mutations may follow an autosomal dominant pattern, where inheriting a single copy of the mutated gene from one parent can increase the risk of developing cancer. In contrast, other mutations may follow a recessive pattern, requiring two copies of the mutated gene (one from each parent) to significantly increase the risk. Therefore, colon cancer is better understood as a multifactorial disease influenced by a combination of genetic, environmental, and lifestyle factors, rather than being classified as strictly dominant or recessive in inheritance.
Is kidney cancer hereditary and what are the symptoms?
Kidney cancer can have both hereditary and non-hereditary causes. While most cases of kidney cancer are not hereditary and are instead influenced by factors like lifestyle, exposure to certain chemicals, and aging, there are hereditary factors that can increase the risk of developing kidney cancer. Hereditary Kidney Cancer Syndromes: Von Hippel-Lindau (VHL) syndrome: This is a rare genetic condition that can increase the risk of developing kidney tumors, as well as tumors in other parts of the body. Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC): Individuals with HLRCC are at an increased risk of developing a specific type of kidney cancer known as hereditary papillary renal carcinoma. Birt-Hogg-Dubé (BHD) syndrome: This genetic condition is associated with an increased risk of developing kidney tumors, as well as skin lesions and lung cysts. Hereditary Nonpolyposis Colorectal Cancer (HNPCC) or Lynch syndrome: While primarily associated with colorectal and uterine cancer, individuals with Lynch syndrome may have a slightly increased risk of kidney cancer. Symptoms of Kidney Cancer: Kidney cancer often does not cause noticeable symptoms in its early stages, and symptoms may not appear until the disease has advanced. Common symptoms of kidney cancer can include: Blood in the urine (hematuria): This is one of the most common signs of kidney cancer. Pain or discomfort in the side or back: This pain may persist and is not due to an injury or strain. A lump or mass in the abdomen or side: Some people may feel a palpable mass or lump in the area of the affected kidney. Unexplained weight loss: Weight loss may occur even if you have not been trying to lose weight. Fatigue: Persistent tiredness or lack of energy can be a symptom of advanced kidney cancer. Loss of appetite. Fever not associated with an infection. Anemia: A low red blood cell count can result in anemia, leading to fatigue and weakness.
Can prostate cancer be atributed to colon cancer?
Prostate cancer and colon cancer are two distinct types of cancer that affect different organs within the body. While they can occur concurrently in the same individual, one is not directly attributed to the other in terms of causality. However, there are some factors that may increase the risk of developing both prostate and colon cancer: Genetic Factors: Some hereditary cancer syndromes, such as Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC), can predispose individuals to both colon and prostate cancer. In these cases, specific genetic mutations increase the likelihood of developing various types of cancer, including those affecting the colon and prostate. Age: Both prostate cancer and colon cancer are more common in older individuals. As age increases, the risk of developing these cancers also rises. Lifestyle Factors: Certain lifestyle habits, such as a diet high in red and processed meats, low intake of fruits and vegetables, lack of physical activity, smoking, and excessive alcohol consumption, are associated with an increased risk of both prostate and colon cancer. Inflammation: Chronic inflammation in the body may contribute to the development of various cancers, including prostate and colon cancer. Conditions such as inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, have been linked to an increased risk of colon cancer. Inflammation of the prostate gland, such as in cases of chronic prostatitis, may also play a role in the development of prostate cancer. While these factors may overlap and increase the risk of developing both prostate and colon cancer, it's essential to understand that each cancer has its unique risk factors, causes, and mechanisms of development. Additionally, early detection through screening and prompt medical intervention are crucial for managing both prostate and colon cancer effectively. If you have concerns about your risk of developing these cancers, it's recommended to discuss them with a healthcare professional who can provide personalized guidance based on your medical history and risk factors.
What causes adrenal gland cancers?
Adrenal gland cancers, also known as adrenocortical carcinomas, are rare and typically occur when normal cells in the adrenal glands change (mutations) in their DNA. These mutations can lead to the uncontrolled growth of cells, forming a cancerous tumor. While the exact causes of these mutations are often unclear, several risk factors and genetic conditions are associated with an increased likelihood of developing adrenal gland cancers. Here are some factors that may contribute: Genetic Predisposition: In some cases, individuals may inherit genetic mutations that increase their susceptibility to adrenal gland cancers. Certain genetic syndromes, such as Li-Fraumeni syndrome and Beckwith-Wiedemann syndrome, have been linked to an elevated risk of adrenal cancer. Hereditary Conditions: Some hereditary conditions, such as hereditary nonpolyposis colorectal cancer (HNPCC) and Lynch syndrome, may be associated with an increased risk of adrenal gland cancers. X-ray Exposure: High doses of radiation, particularly to the abdomen, may increase the risk of developing adrenal cancers. However, this is a rare cause, and most adrenal cancers are not linked to radiation exposure. Age and Gender: Adrenal gland cancers can occur at any age but are most commonly diagnosed in individuals between the ages of 40 and 50. They are slightly more common in women than in men. Li-Fraumeni Syndrome: Li-Fraumeni syndrome is a rare genetic condition that increases the risk of various cancers, including adrenal gland cancers. Individuals with this syndrome have a mutation in the TP53 gene. Beckwith-Wiedemann Syndrome: Beckwith-Wiedemann syndrome is a genetic disorder characterized by overgrowth and an increased risk of certain childhood cancers, including adrenal gland cancers. Carney Complex: Carney complex is a rare genetic syndrome that can be associated with adrenal gland tumors, among other conditions. It is caused by mutations in the PRKAR1A gene. Unknown Factors: In many cases, the exact cause of adrenal gland cancers remains unknown. They often develop sporadically, without a clear genetic or environmental trigger.
Are gallstones hereditary?
my mother died from it and her mother and her sisters all had gall problems, as has my older sister - this finding below infers it passes via the maternal bloodline(maybe a hereditary congenital defect) and females are more likely to be affected - I THINK IT IS hereditary because of my own family, yet because it is so rare most docs look at the overall stats for biliary cancers which are NOT generally hereditary.This was taken from the BMJ (british medical journal) HEPATOBILIARYFamilial liver and gall bladder cancer: a nationwide epidemiological study from SwedenK Hemminki1 and X Li2 1 Department of Biosciences at Novum, Karolinska Institute, 141 57 Huddinge, Sweden, and Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany2 Department of Biosciences at Novum, Karolinska Institute, 141 57 Huddinge, SwedenCorrespondence to:Correspondence to:K Hemminki, CNT Novum, 141 57, Sweden;kari.hemminki@cnt.ki.seABSTRACTBackground and aims: Familial risks in liver and biliary cancers have been assessed in small case control studies, usually based on reported, but not medically verified, cancers in family members. Thus the degree of familial clustering for these cancers remains to be established.Methods: The nationwide Swedish Family-Cancer Database was used, covering 10.2 million individuals for the years 1961-1998 from the Swedish Cancer Registry. Liver and biliary tract cancers were identified from 1121 offspring between the ages of 0 and 66 years and 17 131 parents. Standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated for cancers in family members.Results: All cancers in the liver and biliary system showed a familial SIR of 1.65 (95% CI 1.05-2.46). This was mainly explained by a high risk for familial gall bladder cancer (SIR 5.21 (95% CI 2.07-10.80)) and for familial primary liver cancer with hepatocellular carcinoma histology (SIR 4.69 (95% CI 1.48-11.04)). For gall bladder and hepatocellular cancer, maternal transmission appeared to be favoured. Gall bladder cancer was associated with pancreatic cancer (SIR 2.39 (95% CI 1.23-4.18)). Primary liver cancer was associated with cervical, urinary bladder, and endocrine gland tumours. Cancer in extrahepatic bile ducts was associated with ovarian cancer and that in ampulla of Vater with thyroid cancer; however, these associations may have been fortuitous.Conclusions: This study has provided the first data on familial clustering of liver and gall bladder cancers, based on medically confirmed records. The risks were so high that heritable factors were likely to contribute, possibly modified by environmental factors. The demonstration of candidate genes would help to further characterise the familial risks.Keywords: hepatocellular carcinoma; biliary tract; adenocarcinoma; pancreatic cancer; heritabilityAbbreviations: HNPCC, hereditary non-polyposis colorectal cancer; SIR, standardised incidence ratio; SNOMED, Systematised Nomenclature of Medicine
Colorectal polyps?
Polyps are benign growths of the colon lining. They can be unrelated to cancer, precancerous, or malignant. Polyps, when identified, are removed for diagnosis. If the polyps are benign, the patient should undergo careful surveillance
Colon Cancer Treatment?
Alternative NamesScreening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screeningInformationColon cancer screening can detect polyps and early cancers. Such screening can find abnormalities that can be treated before cancer develops or spreads. Regular screenings may decrease deaths and prevent pain caused by colorectal cancer.TOOLS OR TESTSSeveral tools may be used, either alone or together, to screen for colon cancer:The first method is a stool test that checks your bowel movements for blood.Polyps in the colon and smaller cancers often cause small amounts of bleeding that cannot be seen with the naked eye.The most common method used is the fecal occult blood test(FOBT). Newer stool tests are called the fecal immunochemical test (FIT) and stool DNA test (sDNA).The second method is a sigmoidoscopy exam.This test uses a flexible small scope to look at the lower part of your colon. Because it only looks at the last one-third of the large intestine (colon), it may miss some cancers.A stool test and sigmoidoscopy should be used together.The third method is a colonoscopy. A colonoscopy is similar to a sigmoidoscopy, but the entire colon can be viewed. You will usually be mildly sedated during a colonoscopy.Two other methods may be used:Double-contrast barium enemy, a special x-ray of the large intestine, which includes the colon and rectumVirtual colonoscopy -- a type of x-ray that uses computer software to create an imageA test called capsule endoscopy (swallowing a small, pill-sized camera) is also being studied, but it is not recommended for standard screening at this time.SCREENING FOR AVERAGE-RISK PEOPLEThere is not enough evidence to state which screening method is best. Discuss with your doctor which test is most appropriate for you.Beginning at age 50, both men and women should have a screening test. Some health care providers recommend that African Americans begin screening at age 45.Screening options for patients with an average risk for colon cancer:Colonoscopy every 10 yearsDouble-contrast barium enema every 5 yearsFecal occult blood test (FOBT) every year - if results are positive, a colonoscopy is neededFlexible sigmoidoscopy every 5 - 10 years, usually with stool testing FOBT done every 1 - 3 yearsVirtual colonoscopy every 5 yearsSCREENING FOR HIGHER-RISK PEOPLEPeople with certain risk factors for colon cancer may need earlier (before age 50) or more frequent testing.More common risk factors are:A family history of inherited colorectal cancer syndromes, such as familial adenomatous polyposis (FAP) or hereditary nonpolyposis colorectal cancer (HNPCC)A strong family history of colorectal cancer or polyps. This usually means first-degree relatives (parent, sibling, or child) who developed these conditions younger than age 60.A personal history of colorectal cancer or polypsA personal history of chronic inflammatory bowel disease (for example, ulcerative colitis or Crohn's disease)Screening for these groups of people is more likely to be done using colonoscopy.See also: Colon cancerReferencesWhitlock EP, Lin JS, Liles E, Beil TL, Fu R. Screening for colorectal cancer: a targeted, updated systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2008;149:638-658.Rex DK, Johnson DA, Anderson JC, Schoenfeld PS, Burke CA, Inadomi JM; American College of Gastroenterology. American College of Gastroenterology guidelines for colorectal cancer screening 2009 [corrected]. Am J Gastroenterol. 2009;104:739-750.Lieberman DA. Clinical practice. Screening for colorectal cancer. N Engl J Med. 2009;361:1179-1187.Burt RW, Barthel JS, Dunn KB, et al. NCCN clinical practice guidelines in oncology. Colorectal cancer screening. J Natl Compr Canc Netw. 2010;8:8-61.Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the U.S. Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin. 2008;58:130-160.Reviewed ByReview Date: 11/08/2010George F. Longstreth, MD, Department of Gastroenterology, Kaiser Permanente Medical Care Program, San Diego, California. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
Colon cancer?
DefinitionColon, or colorectal, cancer is cancer that starts in the large intestine (colon) or the rectum (end of the colon).Other types of cancer can affect the colon, such as lymphoma, carcinoid tumors, melanoma, and sarcomas. These are rare. In this article, use of the term "colon cancer" refers to colon carcinoma only.Alternative NamesColorectal cancer; Cancer - colon; Rectal cancer; Cancer-rectum; Adenocarcinoma- colon; Colon -adenocarcinomaCauses, incidence, and risk factorsAccording to the American Cancer Society, colorectal cancer is one of the leading causes of cancer-related deaths in the United States. However, early diagnosis often leads to a complete cure.Almost all colon cancer starts in glands in the lining of the colon and rectum. When most people and when doctors talk about colorectal cancer, this is generally what they are referring to.There is no single cause for colon cancer. Nearly all colon cancers begin as noncancerous (benign) polyps, which slowly develop into cancer.You have a higher risk for colon cancer if you:Are older than 60Are African American and eastern European descentEat a diet high in red or processed meatHave cancer elsewhere in the bodyHave colorectal polypsHave inflammatory bowel disease (Crohn's disease or ulcerative colitis)Have a family history of colon cancerHave a personal history of breast cancerCertain genetic syndromes also increase the risk of developing colon cancer. Two of the most common are hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, and familial adenomatous polyposis (FAP).What you eat may play a role in your risk of colon cancer. Colon cancer may be associated with a high-fat, low-fiber diet and red meat. However, some studies found that the risk does not drop if you switch to a high-fiber diet, so the cause of the link is not yet clear.Smoking cigarettes and drinking alcohol are other risk factors for colorectal cancer.SymptomsMany cases of colon cancer have no symptoms. The following symptoms, however, may indicate colon cancer:Abdominal pain and tenderness in the lower abdomenBlood in the stoolDiarrhea, constipation, or other change in bowel habitsIntestinal obstructionNarrow stoolsUnexplained anemiaWeight losswith no known reasonSigns and testsWith proper screening, colon cancer can be detected before symptoms develop, when it is most curable.Your doctor will perform a physical exam and press on your belly area. The physical exam rarely shows any problems, although the doctor may feel a mass in the abdomen. A rectal exam may reveal a mass in patients with rectal cancer, but not colon cancer.A fecal occult blood test (FOBT) may detect small amounts of blood in the stool, which could suggest colon cancer. However, this test is often negative in patients with colon cancer. For this reason, a FOBT must be done along with colonoscopy or sigmoidoscopy. It is also important to note that a positive FOBT doesn't necessarily mean you have cancer.Imaging tests to diagnose colorectal cancer include:ColonoscopySigmoidoscopyNote: Only colonoscopy can see the entire colon.Blood tests that may be done include:Complete blood count (CBC) to check for anemiaLiver function testsIf your doctor learns that you do have colorectal cancer, more tests will be done to see if the cancer has spread. This is called staging. CT or MRI scans of the abdomen, pelvic area, chest, or brain may be used to stage the cancer. Sometimes, PET scans are also used.Stages of colon cancer are:Stage 0: Very early cancer on the innermost layer of the intestineStage I: Cancer is in the inner layers of the colonStage II: Cancer has spread through the muscle wall of the colonStage III: Cancer has spread to the lymph nodesStage IV: Cancer has spread to other organsBlood tests to detect tumor markers, including carcinoembryonic antigen (CEA) and CA 19-9, may help your physician follow you after treatment.TreatmentTreatment depends partly on the stage of the cancer. In general, treatments may include:Chemotherapy to kill cancer cellsSurgery (most often a colectomy) to remove cancer cellsRadiation therapy to destroy cancerous tissueStage 0 colon cancer may be treated by removing the cancer cells, often during a colonoscopy. For stages I, II, and III cancer, more extensive surgery is needed to remove the part of the colon that is cancerous. (See: Colon resection)There is some debate as to whether patients with stage II colon cancer should receive chemotherapy after surgery. You should discuss this with your oncologist.Almost all patients with stage III colon cancer should receive chemotherapy after surgery for approximately 6 - 8 months. The chemotherapy drug 5-fluorouracil has been shown to increase the chance of a cure in certain patients.Chemotherapy is also used to treat patients with stage IV colon cancer to improve symptoms and prolong survival.Irinotecan, oxaliplatin, capecitabine, and 5-fluorouracil are the three most commonly used drugs.Monoclonal antibodies, including cetuximab (Erbitux), panitumumab (Vectibix), and bevacizumab (Avastin) have been used alone or in combination with chemotherapy.You may receive just one type, or a combination of the drugs.For patients with stage IV disease that has spread to the liver, various treatments directed specifically at the liver can be used. This may include:Burning the cancer (ablation)Cutting out the cancerDelivering chemotherapy or radiation directly into the liverFreezing the cancer (cryotherapy)Although radiation therapy is occasionally used in patients with colon cancer, it is usually used in combination with chemotherapy for patients with stage III rectal cancer.Support GroupsFor additional resources and information, see colon cancer support groups.Expectations (prognosis)Colon cancer is, in many cases, a treatable disease if caught early.How well you do depends on many things, including the stage of the cancer. In general, when treated at an early stage, the vast majority of patients survive at least 5 years after their diagnosis. (This is called the 5-year survival rate.) However, the 5-year survival rate drops considerably once the cancer has spread.If the colon cancer does not come back (recur) within 5 years, it is considered cured. Stage I, II, and III cancers are considered potentially curable. In most cases, stage IV cancer is not curable.ComplicationsBlockage of the colonCancer returning in the colonCancer spreading to other organs or tissues (metastasis)Development of a second primary colorectal cancerCalling your health care providerCall your health care provider if you have:Black, tar-like stoolsBlood during a bowel movementChange in bowel habitsPreventionThe death rate for colon cancer has dropped in the last 15 years. This may be due to increased awareness and screening by colonoscopy.Colon cancer can almost always be caught in its earliest and most curable stages by colonoscopy. Almost all men and women age 50 and older should have a colon cancer screening. Patients at risk may need screening earlier.Colon cancer screening can find precancerous polyps. Removing these polyps may prevent colon cancer.For information, see:Colon cancer screeningColonoscopyDietary and lifestyle modifications are important. Some evidence suggests that low-fat and high-fiber diets may reduce your risk of colon cancer.Several studies have reported that NSAIDs (aspirin, ibuprofen, naproxen, celecoxib) may help reduce the risk of colorectal cancer. However, the U.S. Preventive Services Task Force and the American Cancer Society recommends against taking aspirin or other anti-inflammatory medicines to prevent colon cancer if you have an average risk of the disease -- even if someone in your family has had the condition. Taking more than 300 mg a day of aspirin and similar drugs may cause dangerous gastrointestinal bleeding and heart problems in some people.Although low-dose aspirin may help reduce your risk of other conditions, such as heart disease, it does not lower the rate of colon cancer.ReferencesNational Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. V3.2009.Cuzick J, Otto F, Baron JA, et al. Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol. 2009 May;10(5):501-7.Lieberman DA. Clinical practice. Screening for colorectal cancer. N Engl JMed. 2009 Sep 17;361(12):1179-87.Cappell MS. Pathophysiology, clinical presentation, and management of colon cancer. Gastroenterol Clin North Am. 2008;37:1-24.
