Colorectal cancer
Overview
Colorectal cancer, commonly known as bowel cancer, is a cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 caused by uncontrolled cell growth (neoplasia
Neoplasia
Neoplasm is an abnormal mass of tissue as a result of neoplasia. Neoplasia is the abnormal proliferation of cells. The growth of neoplastic cells exceeds and is not coordinated with that of the normal tissues around it. The growth persists in the same excessive manner even after cessation of the...

), in the colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...

, rectum
Rectum
The rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...

, or vermiform appendix
Vermiform appendix
The appendix is a blind-ended tube connected to the cecum , from which it develops embryologically. The cecum is a pouchlike structure of the colon...

. Colorectal cancer is clinically distinct from anal cancer
Anal cancer
Anal cancer is a type of cancer which arises from the anus, the distal orifice of the gastrointestinal tract. It is a distinct entity from the more common colorectal cancer. The etiology, risk factors, clinical progression, staging, and treatment are all different. Anal cancer is typically a...

, which affects the anus
Anus
The anus is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, unwanted semi-solid matter produced during digestion, which, depending on the type of animal, may be one or more of: matter which the animal cannot digest,...

.

Colorectal cancers start in the lining of the bowel. If left untreated, it can grow into the muscle layers underneath, and then through the bowel wall. Most begin as a small growth on the bowel wall: a colorectal polyp
Colorectal polyp
A colorectal polyp is a polyp occurring on the lining of the colon or rectum. Untreated colorectal polyps can develop into colorectal cancer....

 or adenoma
Adenoma
An adenoma is a benign tumor of glandular origin. Adenomas can grow from many organs including the colon, adrenal glands, pituitary gland, thyroid, prostate, etc. Although these growths are benign, over time they may progress to become malignant, at which point they are called adenocarcinomas...

.
Encyclopedia
Colorectal cancer, commonly known as bowel cancer, is a cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 caused by uncontrolled cell growth (neoplasia
Neoplasia
Neoplasm is an abnormal mass of tissue as a result of neoplasia. Neoplasia is the abnormal proliferation of cells. The growth of neoplastic cells exceeds and is not coordinated with that of the normal tissues around it. The growth persists in the same excessive manner even after cessation of the...

), in the colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...

, rectum
Rectum
The rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...

, or vermiform appendix
Vermiform appendix
The appendix is a blind-ended tube connected to the cecum , from which it develops embryologically. The cecum is a pouchlike structure of the colon...

. Colorectal cancer is clinically distinct from anal cancer
Anal cancer
Anal cancer is a type of cancer which arises from the anus, the distal orifice of the gastrointestinal tract. It is a distinct entity from the more common colorectal cancer. The etiology, risk factors, clinical progression, staging, and treatment are all different. Anal cancer is typically a...

, which affects the anus
Anus
The anus is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, unwanted semi-solid matter produced during digestion, which, depending on the type of animal, may be one or more of: matter which the animal cannot digest,...

.

Colorectal cancers start in the lining of the bowel. If left untreated, it can grow into the muscle layers underneath, and then through the bowel wall. Most begin as a small growth on the bowel wall: a colorectal polyp
Colorectal polyp
A colorectal polyp is a polyp occurring on the lining of the colon or rectum. Untreated colorectal polyps can develop into colorectal cancer....

 or adenoma
Adenoma
An adenoma is a benign tumor of glandular origin. Adenomas can grow from many organs including the colon, adrenal glands, pituitary gland, thyroid, prostate, etc. Although these growths are benign, over time they may progress to become malignant, at which point they are called adenocarcinomas...

. These mushroom-shaped growths are usually benign, but some develop into cancer over time. Localized bowel cancer is usually diagnosed through colonoscopy
Colonoscopy
Colonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...

.

Invasive cancers that are confined within the wall of the colon (T stages I and II) are often curable with surgery, For example, in England over 90% of patients diagnosed at this stage will survive the disease beyond 5 years. However, if left untreated, the cancer can spread to regional lymph nodes (stage III). In England, around 48% of patients diagnosed at this stage survive the disease beyond five years. Cancer that has spread widely around the body (stage IV) is usually not curable; approximately 7% of patients in England diagnosed at this stage survive beyond five years.

Colorectal cancer is the third most commonly diagnosed cancer in the world, but it is more common in developed countries
Developed country
A developed country is a country that has a high level of development according to some criteria. Which criteria, and which countries are classified as being developed, is a contentious issue...

. Around 60% of cases were diagnosed in the developed world. GLOBOCAN estimated that, in 2008, 1.24 million new cases of colorectal cancer were clinically diagnosed, and that this type of cancer killed 610,000 people.

Signs and symptoms

The symptoms of colorectal cancer depend on the location of tumor in the bowel, and whether it has spread elsewhere in the body (metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

). While no symptom is diagnostic of colorectal cancer, rectal bleeding or anemia are high risk features.

Local

Local symptoms are more likely if the tumor is located closer to the anus. There may be a change in bowel habit (such as unusual and unexplained constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...

 or diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

), and a feeling of incomplete defecation (rectal tenesmus). Lower gastrointestinal bleeding
Lower gastrointestinal bleeding
Lower gastrointestinal bleeding, commonly abbreviated LGIB, refers to any form of bleeding in the lower gastrointestinal tract. LGIB is a common ailment seen at emergency departments. It presents less commonly than upper gastrointestinal bleeding . It is estimated that UGIB accounts for 100-200 per...

, including the passage of bright red blood in the stool, may indicate colorectal cancer, as may the increased presence of mucus
Mucus
In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...

. Melena
Melena
In medicine, melena or melaena refers to the black, "tarry" feces that are associated with gastrointestinal hemorrhage. The black color is caused by oxidation of the iron in hemoglobin during its passage through the ileum and colon.-Melena vs...

, black stool with a tarry appearance, normally occurs in upper gastrointestinal bleeding
Upper gastrointestinal bleeding
Upper gastrointestinal bleeding refers to hemorrhage in the upper gastrointestinal tract. The anatomic cut-off for upper GI bleeding is the ligament of Treitz, which connects the fourth portion of the duodenum to the diaphragm near the splenic flexure of the colon.Upper GI bleeds are considered...

 (such as from a duodenal ulcer), but is sometimes encountered in colorectal cancer when the disease is located in the beginning of the large bowel.

A tumor that is large enough to fill the entire lumen
Lumen (anatomy)
A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...

 of the bowel may cause bowel obstruction
Bowel obstruction
Bowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...

. This situation is characterized by constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...

, abdominal pain
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...

, abdominal distension
Abdominal distension
Abdominal distension is a sensation of elevated abdominal pressure and volume. It is estimated that close to 25% of the US population has some degree of abdominal distension on a regular basis. Some describe it as belching, others claim they feel nausea and yet others say they pass excessive gas...

 and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

. This occasionally leads to the obstructed and distended bowel perforating
Gastrointestinal perforation
Gastrointestinal perforation is a complete penetration of the wall of the stomach, small intestine or large bowel, resulting in intestinal contents flowing into the abdominal cavity. Perforation of the intestines results in the potential for bacterial contamination of the abdominal cavity...

 and causing peritonitis
Peritonitis
Peritonitis is an inflammation of the peritoneum, the serous membrane that lines part of the abdominal cavity and viscera. Peritonitis may be localised or generalised, and may result from infection or from a non-infectious process.-Abdominal pain and tenderness:The main manifestations of...

. A large left colonic tumor may compress the left ureter and cause hydronephrosis
Hydronephrosis
Hydronephrosis is distension and dilation of the renal pelvis calyces, usually caused by obstruction of the free flow of urine from the kidney, leading to progressive atrophy of the kidney...

.

Certain local effects of colorectal cancer occur when the disease has become more advanced. A large tumor is more likely to be noticed on feeling the abdomen, and it may be noticed by a doctor on physical examination
Physical examination
Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...

. The disease may invade other organs, and may cause blood
Hematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...

 or air in the urine
Pneumaturia
Pneumaturia is the passage of gas or "air" in urine. This may be seen or described as "bubbles in the urine".-Causes:A common cause of pneumaturia is vesico-colic fistulae...

 (invasion of the bladder
Bladder
Bladder usually refers to an anatomical hollow organBladder may also refer to:-Biology:* Urinary bladder in humans** Urinary bladder ** Bladder control; see Urinary incontinence** Artificial urinary bladder, in humans...

) or vaginal discharge
Vaginal discharge
Vaginal discharge is term given to biological fluids contained within or expelled from the vagina.While most discharge is normal and can reflect the various stages of a woman's cycle, some discharge can be a result of an infection, such as a sexually transmitted disease.The term blennorrhea is...

 (invasion of the female reproductive tract
Female reproductive system (human)
The female reproductive system contains two main parts: the uterus, which hosts the developing fetus, produces vaginal and uterine secretions, and passes the anatomically male person's sperm through to the fallopian tubes; and the ovaries, which produce the anatomically female person's egg cells...

).

Constitutional

If a tumor has caused chronic bleeding in the bowel, iron deficiency anemia
Iron deficiency anemia
Iron-deficiency anemia is a common anemia that occurs when iron loss occurs, and/or the dietary intake or absorption of iron is insufficient...

 may occur, causing a range of symptoms that may include fatigue, palpitations and pale skin (pallor
Pallor
Pallor is a reduced amount of oxyhaemoglobin in skin or mucous membrane, a pale color which can be caused by illness, emotional shock or stress, stimulant use, lack of exposure to sunlight, anaemia or genetics....

). Colorectal cancer may also lead to weight loss, generally due to a decreased appetite
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...

 .

There may be rarer symptoms including unexplained fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

 or thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...

, usually deep vein thrombosis
Deep vein thrombosis
Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...

. Such symptoms, known as paraneoplastic syndrome
Paraneoplastic syndrome
A paraneoplastic syndrome is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells. These phenomena are mediated by humoral factors excreted by tumor cells or by an immune response against the tumor...

, are due to the body's immune response to the cancer, rather than the tumor itself.

Risk factors

The lifetime risk of developing colon cancer in the United States is about 7%. Certain factors increase a person's risk of developing the disease. These include:
  • Age: The risk of developing colorectal cancer increases with age. Most cases occur in the 60s and 70s, while cases before age 50 are uncommon unless a family history of early colon cancer is present.
  • Polyps
    Colorectal polyp
    A colorectal polyp is a polyp occurring on the lining of the colon or rectum. Untreated colorectal polyps can develop into colorectal cancer....

     of the colon, particularly adenomatous polyps, are a risk factor for colon cancer. The removal of colon polyps at the time of colonoscopy reduces the subsequent risk of colon cancer. Larger and those with greater surface area (villous polyps compared to tubular) are more likely to undergo neoplasia due to the greater likelyhood of one of these cells undergoing the series of malignant transformations into cancer.
  • History of cancer. Individuals who have previously been diagnosed and treated for colon cancer are at risk for developing colon cancer in the future. Women who have had cancer of the ovary
    Ovarian cancer
    Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....

    , uterus
    Uterine cancer
    The term uterine cancer may refer to any of several different types of cancer which occur in the uterus, namely:*Uterine sarcomas: sarcomas of the myometrium, or muscular layer of the uterus, are most commonly leiomyosarcomas.*Endometrial cancer:...

    , or breast
    Breast cancer
    Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

     are at higher risk of developing colorectal cancer.
  • Heredity:
    • Family history of colon cancer, especially in a close relative before the age of 55 or multiple relatives.
    • Familial adenomatous polyposis
      Familial adenomatous polyposis
      Familial adenomatous polyposis is an inherited condition in which numerous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs when not treated....

       (FAP) carries a near 100% risk of developing colorectal cancer by the age of 40 if untreated
    • Hereditary nonpolyposis colorectal cancer
      Hereditary nonpolyposis colorectal cancer
      Lynch syndrome is an autosomal dominant genetic condition which has a high risk of colon cancer as well as other cancers including endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin...

       (HNPCC) or Lynch syndrome
    • Gardner syndrome
  • Smoking: Smokers are more likely to die of colorectal cancer than nonsmokers. An American Cancer Society
    American Cancer Society
    The American Cancer Society is the "nationwide community-based voluntary health organization" dedicated, in their own words, "to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer, through research, education, advocacy, and...

     study found "Women who smoked were more than 40% more likely to die from colorectal cancer than women who never had smoked. Male smokers had more than a 30% increase in risk of dying from the disease compared to men who never had smoked."
  • Diet: Studies show that a diet high in red meat and low in fresh fruit, vegetables, poultry and fish increases the risk of colorectal cancer. In June 2005, a study by the European Prospective Investigation into Cancer and Nutrition
    European Prospective Investigation into Cancer and Nutrition
    The European Prospective Investigation into Cancer and Nutrition study is a Europe-wide prospective cohort study of the relationships between diet and cancer, as well as other chronic diseases, such as cardiovascular disease...

     suggested that diets high in red and processed meat, as well as those low in fiber, are associated with an increased risk of colorectal cancer. Individuals who frequently eat fish showed a decreased risk. However, other studies have cast doubt on the claim that diets high in fiber decrease the risk of colorectal cancer; rather, low-fiber diet was associated with other risk factors, leading to confounding
    Confounding
    In statistics, a confounding variable is an extraneous variable in a statistical model that correlates with both the dependent variable and the independent variable...

    . The nature of the relationship between dietary fiber and risk of colorectal cancer remains controversial.
  • Lithocholic acid
    Lithocholic acid
    Lithocholic acid is a bile acid that acts as a detergent to solubilize fats for absorption. It is made from chenodeoxycholic acid by bacterial action in the colon.It has been implicated in human and experimental animal carcinogenesis....

    : Lithocholic acid is a bile acid
    Bile acid
    Bile acids are steroid acids found predominantly in the bile of mammals. Bile salts are bile acids compounded with a cation, usually sodium. In humans, the salts of taurocholic acid and glycocholic acid represent approximately eighty percent of all bile salts. The two major bile acids are cholic...

     that acts as a detergent to solubilize fats for absorption. It is made from chenodeoxycholic acid
    Chenodeoxycholic acid
    Chenodeoxycholic acid is a bile acid. It occurs as a white crystalline substance insoluble in water but soluble in alcohol and acetic acid, with melting point at 165-167 °C. Salts of this carboxylic acid are called chenodeoxycholates...

     by bacterial action in the colon
    Colon (anatomy)
    The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...

    . It has been implicated in human and experimental animal carcinogenesis. Carbonic acid
    Carbonic acid
    Carbonic acid is the inorganic compound with the formula H2CO3 . It is also a name sometimes given to solutions of carbon dioxide in water, because such solutions contain small amounts of H2CO3. Carbonic acid forms two kinds of salts, the carbonates and the bicarbonates...

     type surfactant
    Surfactant
    Surfactants are compounds that lower the surface tension of a liquid, the interfacial tension between two liquids, or that between a liquid and a solid...

    s easily combine with calcium
    Calcium
    Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

     ion and become detoxication
    Detoxication
    Detoxication products are the major metabolites formed from most drug metabolism.There are two common patterns observed:#A drug with potent pharmacological activity is converted to a major metabolite with markedly reduced or no pharmacological activity #A drug is converted to a metabolite with...

     products.
  • Physical inactivity: People who are physically active are at lower risk of developing colorectal cancer.
  • Viruses: Exposure to some viruses (such as particular strains of human papilloma virus) may be associated with colorectal cancer.
  • Primary sclerosing cholangitis
    Primary sclerosing cholangitis
    Primary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis, liver failure and liver cancer...

     offers a risk independent to ulcerative colitis
    Ulcerative colitis
    Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

    .
  • Low levels of selenium
    Selenium
    Selenium is a chemical element with atomic number 34, chemical symbol Se, and an atomic mass of 78.96. It is a nonmetal, whose properties are intermediate between those of adjacent chalcogen elements sulfur and tellurium...

  • Inflammatory bowel disease: About one percent of colorectal cancer patients have a history of chronic ulcerative colitis
    Ulcerative colitis
    Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

    . The risk of developing colorectal cancer varies inversely with the age of onset of the colitis and directly with the extent of colonic involvement and the duration of active disease. Patients with colorectal Crohn's disease
    Crohn's disease
    Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

     have a more than average risk of colorectal cancer, but less than that of patients with ulcerative colitis.
  • Environmental factors. Industrialized countries are at a relatively increased risk compared to less developed countries that traditionally had high-fiber/low-fat diets. Studies of migrant populations have revealed a role for environmental factors, particularly dietary, in the etiology of colorectal cancers.
  • Exogenous hormones. The differences in the time trends in colorectal cancer in males and females could be explained by cohort effects in exposure to some gender-specific risk factor; one possibility that has been suggested is exposure to estrogens. There is, however, little evidence of an influence of endogenous hormones on the risk of colorectal cancer. In contrast, there is evidence that exogenous estrogens such as hormone replacement therapy (HRT)
    Hormone replacement therapy (menopause)
    Hormone replacement therapy is a system of medical treatment for surgically menopausal, perimenopausal and to a lesser extent postmenopausal women...

    , tamoxifen
    Tamoxifen
    Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...

    , or oral contraceptives might be associated with colorectal tumors.
  • Alcohol: Drinking, especially heavily, may be a risk factor.
  • Vitamin B6
    Vitamin B6
    Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...

     intake lowers the risk of colorectal cancer.

Alcohol

The WCRF
World Cancer Research Fund
World Cancer Research Fund International is a not-for-profit association, established by royal decree in Belgium, with headquarters in London, UK...

 panel report Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective
Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective
Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective, also known as the Expert Report, was an expert report published by the World Cancer Research Fund global network in 2007....

finds the evidence "convincing" that alcoholic drinks increase the risk of colorectal cancer in men.

The NIAAA reports that: "Epidemiologic studies have found a small but consistent dose-dependent association between alcohol consumption and colorectal cancer even when controlling for fiber and other dietary factors. Despite the large number of studies, however, causality cannot be determined from the available data."

"Heavy alcohol use may also increase the risk of colorectal cancer" (NCI). One study found that "People who drink more than 30 grams of alcohol per day (and especially those who drink more than 45 grams per day) appear to have a slightly higher risk for colorectal cancer." Another found that "The consumption of one or more alcoholic beverages a day at baseline was associated with approximately a 70% greater risk of colon cancer."

One study found "While there was a more than twofold increased risk of significant colorectal neoplasia in people who drink spirits and beer, people who drank wine had a lower risk. In our sample, people who drank more than eight servings of beer or spirits per week had at least a one in five chance of having significant colorectal neoplasia detected by screening colonoscopy.".

Other research suggests "to minimize your risk of developing colorectal cancer, it's best to drink in moderation."

On its colorectal cancer page, the National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...

 does not list alcohol as a risk factor; however, on another page it states, "Heavy alcohol use may also increase the risk of colorectal cancer".

Drinking may be a cause of earlier onset of colorectal cancer.

Pathogenesis

Colorectal cancer is a disease originating from the epithelial cells
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

 lining the colon or rectum of the gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....

, most frequently as a result of mutations in the Wnt signaling pathway
Wnt signaling pathway
The Wnt signaling pathway is a network of proteins best known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals.-Discovery:...

 that artificially increase signaling activity. The mutations can be inherited or are acquired
Somatic cell
A somatic cell is any biological cell forming the body of an organism; that is, in a multicellular organism, any cell other than a gamete, germ cell, gametocyte or undifferentiated stem cell...

, and must probably occur in the intestinal crypt stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...

. The most commonly mutated gene in all colorectal cancer is the APC gene, which produces the APC protein. The APC protein is a "brake" on the accumulation of β-catenin protein; without APC, β-catenin accumulates to high levels and translocates (moves) into the nucleus, binds to DNA, and activates the transcription of genes that are normally important for stem cell renewal and differentiation but when inappropriately expressed at high levels can cause cancer. While APC is mutated in most colon cancers, some cancers have increased β-catenin because of mutations in β-catenin (CTNNB1) that block its degradation, or they have mutation(s) in other genes with function analogous to APC such as AXIN1
AXIN1
Axin-1 is a protein that in humans is encoded by the AXIN1 gene.-Interactions:AXIN1 has been shown to interact with Beta-catenin, GSK3B, TSC2, APC, LRP5, DVL1, MAP3K1, CSNK1E, Casein kinase 1, alpha 1 and PPP2R5A.-Further reading:...

, AXIN2
AXIN2
Axin-2 also known as axin-like protein or axis inhibition protein 2 or conductin is a protein that in humans is encoded by the AXIN2 gene.- Function :...

, TCF7L2
TCF7L2
Transcription factor 7-like 2 also known as TCF7L2 or TCF4 is a protein acting as a transcription factor. In humans this protein is encoded by the TCF7L2 gene...

, or NKD1.

Beyond the defects in the Wnt-APC-beta-catenin signaling pathway, other mutations must occur for the cell to become cancerous. The p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...

 protein, produced by the TP53 gene, normally monitors cell division and kills
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

 cells if they have Wnt pathway defects. Eventually, a cell line acquires a mutation in the TP53 gene and transforms the tissue from an adenoma into an invasive carcinoma. (Sometimes the gene encoding p53 is not mutated, but another protective protein named BAX is.)

Other apoptotic proteins commonly deactivated in colorectal cancers are TGF-β and DCC (Deleted in Colorectal Cancer
Deleted in Colorectal Cancer
Deleted in Colorectal Carcinoma, also known as DCC, is a protein which in humans is encoded by the DCC gene. DCC has long been implicated in colorectal cancer. While the official, full name of this gene is Deleted in Colorectal Carcinoma, it is almost universally called Deleted in Colorectal Cancer...

). TGF-β has a deactivating mutation in at least half of colorectal cancers. Sometimes TGF-β is not deactivated, but a downstream protein named SMAD
SMAD
SMAD may refer to:* Sowjetische Militäradministration in Deutschland* SMAD – proteins involved in cell signaling** R-SMAD – receptor regulated SMAD proteins** I-SMAD – inhibitory SMAD proteins...

 is. DCC commonly has deletion of its chromosome segment in colorectal cancer.

Some genes are oncogenes - they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS
KRAS
GTPase KRas also known as V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog and KRAS, is a protein that in humans is encoded by the KRAS gene. Like other members of the Ras family, the KRAS protein is a GTPase and is an early player in many signal transduction pathways...

, RAF
RAF (disambiguation)
-Military and Paramilitary Organisations:* Royal Air Force, the air force of the United Kingdom* Rapid Action Force, India's elite paramilitary police force* Royal Aircraft Factory, former name of the Royal Aircraft Establishment...

, and PI3K, which normally stimulate the cell to divide in response to growth factors, can acquire mutations that result in over-activation of cell proliferation. The chronological order of mutations is sometimes important, with a primary KRAS mutation generally leading to a self-limiting hyperplastic or borderline lesion, but if occurring after a previous APC mutation it often progresses to cancer. PTEN
PTEN
PTEN may mean:* Patterson-UTI Energy, Inc., which trades on the NASDAQ stock market under the symbol 'PTEN'* Prime Time Entertainment Network* PTEN , a human tumour suppressor gene on chromosome 10...

, a tumor suppressor, normally inhibits PI3K, but can sometimes become mutated and deactivated.

Diagnosis

Colorectal cancer can take many years to develop and early detection of colorectal cancer greatly improves the chances of a cure. The National Cancer Policy Board of the Institute of Medicine
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...

 estimated in 2003 that even modest efforts to implement colorectal cancer screening methods would result in a 29 percent drop in cancer deaths in 20 years. Despite this, colorectal cancer screening rates remain low. Therefore, screening for the disease is recommended in individuals who are at increased risk. There are several different tests available for this purpose.
  • Digital rectal exam (DRE): The doctor inserts a lubricated, gloved finger into the rectum to feel for abnormal areas. It only detects tumors large enough to be felt in the distal part of the rectum but is useful as an initial screening test.
  • Fecal occult blood
    Fecal occult blood
    Fecal occult blood refers to blood in the feces that is not visibly apparent. A fecal occult blood test checks for hidden blood in the stool...

     test (FOBT): a test for blood in the stool. Two types of tests can be used for detecting occult blood in stools i.e. guaiac based (chemical test) and immunochemical. The sensitivity of immunochemical testing is superior to that of chemical testing without an unacceptable reduction in specifity.
  • M2-PK
    Tumor M2-PK
    Tumor M2-PK is a synonym for the dimeric form of the pyruvate kinase isoenzyme type M2 , a key enzyme within tumor metabolism. Tumor M2-PK can be elevated in many tumor types, rather than being an organ-specific tumor marker such as PSA...

    : a CE marked stool test which indicates colorectal polyps, colorectal cancer, acute and chronic inflammatory bowel disease and other diseases of the digestive tract. The test result is not affected by any foods, so no dietary restrictions are necessary before taking the stool sample. It detects bleeding and non-bleeding colorectal polyps and tumors and has significantly superior sensitivity compared to conventional occult blood tests. The amount of M2-PK in stool can be quantified in 4 mg of feces either by ELISA
    ELISA
    Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...

     or with a Point-of-Care Rapid Test.
  • Endoscopy
    Endoscopy
    Endoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...

    :
    • Sigmoidoscopy
      Sigmoidoscopy
      Sigmoidoscopy From Greek Sigma - eidos - scopy, to look inside an s-like object, is the minimally invasive medical examination of the large intestine from the rectum through the last part of the colon. There are two types of sigmoidoscopy, flexible sigmoidoscopy, which uses a flexible endoscope,...

      : A lighted probe (sigmoidoscope) is inserted into the rectum and lower colon to check for polyps and other abnormalities.
    • Colonoscopy
      Colonoscopy
      Colonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...

      : A lighted probe called a colonoscope is inserted into the rectum and the entire colon to look for polyp
      Polyp (medicine)
      A polyp is an abnormal growth of tissue projecting from a mucous membrane. If it is attached to the surface by a narrow elongated stalk, it is said to be pedunculated. If no stalk is present, it is said to be sessile. Polyps are commonly found in the colon, stomach, nose, sinus, urinary bladder...

      s and other abnormalities that may be caused by cancer. A colonoscopy has the advantage that if polyp
      Polyp (medicine)
      A polyp is an abnormal growth of tissue projecting from a mucous membrane. If it is attached to the surface by a narrow elongated stalk, it is said to be pedunculated. If no stalk is present, it is said to be sessile. Polyps are commonly found in the colon, stomach, nose, sinus, urinary bladder...

      s are found during the procedure they can be removed immediately. Tissue can also be taken for biopsy
      Biopsy
      A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...

      .

In the United States, colonoscopy or FOBT plus sigmoidoscopy are the preferred screening options.

Other screening methods

  • Double contrast barium enema (DCBE): First, an overnight preparation is taken to cleanse the colon. An enema
    Enema
    An enema is the procedure of introducing liquids into the rectum and colon via the anus. The increasing volume of the liquid causes rapid expansion of the lower intestinal tract, often resulting in very uncomfortable bloating, cramping, powerful peristalsis, a feeling of extreme urgency and...

     containing barium sulfate
    Barium sulfate
    Barium sulfate is the inorganic compound with the chemical formula BaSO4. It is a white crystalline solid that is odorless and insoluble in water. It occurs as the mineral barite, which is the main commercial source of barium and materials prepared from it...

     is administered, then air is insufflated into the colon, distending it. The result is a thin layer of barium over the inner lining of the colon which is visible on X-ray films. A cancer or a precancerous polyp can be detected this way. This technique can miss the (less common) flat polyp.
  • Virtual colonoscopy
    Virtual colonoscopy
    Virtual colonoscopy is a medical imaging procedure which uses x-rays and computers to produce two- and three-dimensional images of the colon from the lowest part, the rectum, all the way to the lower end of the small intestine and display them on a screen...

     replaces X-ray films in the double contrast barium enema (above) with a special computed tomography
    Computed tomography
    X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

     scan and requires special workstation software in order for the radiologist to interpret. This technique is approaching colonoscopy
    Colonoscopy
    Colonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...

     in sensitivity for polyps. However, any polyps found must still be removed by standard colonoscopy.
  • Standard computed axial tomography is an x-ray method that can be used to determine the degree of spread of cancer, but is not sensitive enough to use for screening. Some cancers are found in CAT scans performed for other reasons.
  • Blood tests: Measurement of the patient's blood for elevated levels of certain proteins can give an indication of tumor load. In particular, high levels of carcinoembryonic antigen
    Carcinoembryonic antigen
    Carcinoembryonic antigen is a glycoprotein involved in cell adhesion. It is normally produced during fetal development, but the production of CEA stops before birth. Therefore, it is not usually present in the blood of healthy adults, although levels are raised in heavy smokers...

     (CEA) in the blood can indicate metastasis
    Metastasis
    Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

     of adenocarcinoma
    Adenocarcinoma
    Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...

    . These tests are frequently false positive
    Type I and type II errors
    In statistical test theory the notion of statistical error is an integral part of hypothesis testing. The test requires an unambiguous statement of a null hypothesis, which usually corresponds to a default "state of nature", for example "this person is healthy", "this accused is not guilty" or...

     or false negative
    Type I and type II errors
    In statistical test theory the notion of statistical error is an integral part of hypothesis testing. The test requires an unambiguous statement of a null hypothesis, which usually corresponds to a default "state of nature", for example "this person is healthy", "this accused is not guilty" or...

    , and are not recommended for screening, it can be useful to assess disease recurrence. CA19-9
    CA19-9
    CA19-9 is a tumor marker that is used primarily in the management of pancreatic cancer.-History:...

     and CA 242
    CA 242 (tumor marker)
    CA 242 is a tumor marker for sialylated Lewis carbohydrates associated with adenocarcinomas and e-selectin mediated metastatic risk....

     biomarkers can indicate e-selectin
    E-selectin
    E-selectin, also known as CD62 antigen-like family member E , endothelial-leukocyte adhesion molecule 1 , or leukocyte-endothelial cell adhesion molecule 2 , is a cell adhesion molecule expressed only on endothelial cells activated by cytokines. Like other selectins, it plays an important part in...

     related metastatic risks, help follow therapeutic progress, and assess disease recurrence. Also the level of tissue inhibitor of metalloproteinases
    Tissue inhibitor of metalloproteinases
    The matrix metalloproteinases are inhibited by specific endogenous tissue inhibitors of metalloproteinases , which comprise a family of four protease inhibitors: TIMP1, TIMP2, TIMP3 and TIMP4....

     1 (TIMP1
    TIMP1
    TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a glycoprotein that is expressed from the several tissues of organisms....

    ) in the blood has been shown to correlate with the occurrence of colon cancer. A TIMP1
    TIMP1
    TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a glycoprotein that is expressed from the several tissues of organisms....

     test can be helpful in an evaluation to assess the risk of having developed colorectal cancer. TIMP1
    TIMP1
    TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a glycoprotein that is expressed from the several tissues of organisms....

     is particularly helpful as a marker for early identification of colorectal cancer, where it has been shown to have a high specificity and sensitivity. The research of TIMP1
    TIMP1
    TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a glycoprotein that is expressed from the several tissues of organisms....

    , as a marker for early identification of colorectal cancer, is particularly focused in Denmark as a collaboration between the University of Copenhagen
    University of Copenhagen
    The University of Copenhagen is the oldest and largest university and research institution in Denmark. Founded in 1479, it has more than 37,000 students, the majority of whom are female , and more than 7,000 employees. The university has several campuses located in and around Copenhagen, with the...

    , the Technical University of Denmark
    Technical University of Denmark
    The Technical University of Denmark , often simply referred to as DTU, is a university just north of Copenhagen, Denmark. It was founded in 1829 at the initiative of Hans Christian Ørsted as Denmark's first polytechnic, and is today ranked among Europe's leading engineering institutions, and the...

    , Rigshospitalet
    Rigshospitalet
    Rigshospitalet - Copenhagen University Hospital, or simply Riget, is the national hospital of Denmark, located in the capital city of Copenhagen, between the streets of Blegdamsvej, Tagensvej and Nørre Allé...

     and Cancer Marker A/S, which is a Danish medico-company.
  • Cell free DNA - Blood: There is extensive literature describing DNA shed from tumors circulating as cell free DNA in the blood. Using highly sensitive assays, studies report the presence of DNA mutations and DNA methylation tumor markers such as SEPT9
    SEPT9
    Septin-9 is a protein that in humans is encoded by the SEPT9 gene.-Interactions:SEPT9 has been shown to interact with SEPT2 and SEPT7.-Biology:...

     in the plasma of colon cancer patients. In Europe, the SEPT9
    SEPT9
    Septin-9 is a protein that in humans is encoded by the SEPT9 gene.-Interactions:SEPT9 has been shown to interact with SEPT2 and SEPT7.-Biology:...

     methylation marker has been developed into the CE marked Epi proColon test (Epigenomics AG
    Epigenomics AG
    Epigenomics is a molecular diagnostics company headquartered in Berlin, Germany with a wholly owned subsidiary, Epigenomics Inc. based in Seattle, WA.-History:...

    ) and the ms9 test (Abbott Molecular). It is also the subject of a clinical trial in the US, and has been licensed for the development of LDT tests by Quest Diagnostics and ARUP Laboratories
    ARUP Laboratories
    ARUP Laboratories is a leading national reference laboratory and a nonprofit enterprise of the University of Utah and its Department of Pathology. ARUP offers more than 3,000 tests and test combinations, ranging from routine screening tests to highly esoteric molecular and genetic assays...

     in the US, and Warnex Laboratories in Canada.
  • Genetic counseling
    Genetic counseling
    Genetic counseling or traveling is the process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning...

     and genetic testing
    Genetic testing
    Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...

     for families who may have a hereditary form of colon cancer, such as hereditary nonpolyposis colorectal cancer
    Hereditary nonpolyposis colorectal cancer
    Lynch syndrome is an autosomal dominant genetic condition which has a high risk of colon cancer as well as other cancers including endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin...

     (HNPCC) or familial adenomatous polyposis
    Familial adenomatous polyposis
    Familial adenomatous polyposis is an inherited condition in which numerous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs when not treated....

     (FAP).
  • Positron emission tomography
    Positron emission tomography
    Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...

     (PET) is a 3-dimensional scanning technology where a radioactive sugar is injected into the patient, the sugar collects in tissues with high metabolic activity, and an image is formed by measuring the emission of radiation from the sugar. Because cancer cells often have very high metabolic rates, this can be used to differentiate benign and malignant tumors. PET is not used for screening and does not (yet) have a place in routine workup of colorectal cancer cases.
  • Whole-body PET imaging is the most accurate diagnostic test for detection of recurrent colorectal cancer, and is a cost-effective way to differentiate resectable from nonresectable disease. A PET scan is indicated whenever a major management decision depends upon accurate evaluation of tumour presence and extent.
  • Stool DNA testing is an emerging technology in screening for colorectal cancer. Premalignant adenomas and cancers shed DNA markers from their cells which are not degraded during the digestive process and remain stable in the stool. Capture, followed by PCR
    Polymerase chain reaction
    The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....

     amplifies the DNA to detectable levels for assay. Clinical studies have shown a cancer detection sensitivity of 71%–91%.
  • High C-Reactive Protein levels is risk marker.
  • miRNA
    Mirna
    Mirna may refer to:geographical entities* Mirna , a river in Istria, Croatia* Mirna , a river in Slovenia, tributary of the river Sava* Mirna , a settlement in the municipality of Mirna in Southeastern Sloveniapeople...

    -profiling-based screening for detection of early-stage colorectal cancer: The life science and research company Exiqon A/S has developed a novel plasma miRNA screening assay for identifying early-stage colorectal cancer. Plasma miRNA has been shown to be a promising biomarker for many diseases including cancer. The goal of this technique is to select individuals for colonoscopy rather than to replace colonoscopy as the gold standard of colorectal cancer diagnosis. Blood plasma samples collected from patients with early, resectable (Stage II) colorectal cancer and sex-and age-matched healthy volunteers were profiled. So far potential biomarkers have shown promising specificity and sensitivity. The same technology can also be applied to patients who may be at higher risk of relapse and therefore in need for more aggressive adjuvant chemotherapy.

Monitoring

Carcinoembryonic antigen
Carcinoembryonic antigen
Carcinoembryonic antigen is a glycoprotein involved in cell adhesion. It is normally produced during fetal development, but the production of CEA stops before birth. Therefore, it is not usually present in the blood of healthy adults, although levels are raised in heavy smokers...

 (CEA) is a protein found on virtually all colorectal tumors. CEA may be used to monitor and assess response to treatment in patients with metastatic disease. CEA can also be used to monitor recurrence in patients post-operatively.

Tissue Inhibitor of Metalloproteinases
Tissue inhibitor of metalloproteinases
The matrix metalloproteinases are inhibited by specific endogenous tissue inhibitors of metalloproteinases , which comprise a family of four protease inhibitors: TIMP1, TIMP2, TIMP3 and TIMP4....

 1 (TIMP1
TIMP1
TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a glycoprotein that is expressed from the several tissues of organisms....

) is also possible to be used as a monitor and assess response to treatment of coloreactal cancer. Particular when it is combined with (CEA). Constantly increased levels of TIMP1
TIMP1
TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a glycoprotein that is expressed from the several tissues of organisms....

 during treatment identify patients with a very poor prognosis.

M2-PK EDTA- Plasma Test. M2-PK may be used to monitor and assess response to treatment of colorectal cancer.

Pathology

The pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....

 of the tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

 is usually reported from the analysis of tissue taken from a biopsy or surgery. A pathology report will usually contain a description of cell type
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...

 and grade. The most common colon cancer cell type is adenocarcinoma
Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...

 which accounts for 95% of cases. Other, rarer types include lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...

 and squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...

.

Cancers on the right side (ascending colon and cecum
Cecum
The cecum or caecum is a pouch, connecting the ileum with the ascending colon of the large intestine. It is separated from the ileum by the ileocecal valve or Bauhin's valve, and is considered to be the beginning of the large intestine. It is also separated from the colon by the cecocolic...

) tend to be exophytic, that is, the tumour grows outwards from one location in the bowel wall. This very rarely causes obstruction of feces
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...

, and presents with symptoms such as anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

. Left-sided tumours tend to be circumferential, and can obstruct the bowel much like a napkin ring.

Adenocarcinoma is a malignant epithelial tumor, originating from glandular epithelium of the colorectal mucosa. It invades the wall, infiltrating the muscularis mucosae
Muscularis mucosae
The lamina muscularis mucosae is the thin layer of smooth muscle found in most parts of the gastrointestinal tract, located outside the lamina propria mucosae and separating it from the submucosa....

, the submucosa
Submucosa
In the gastrointestinal tract, the submucosa is the layer of dense irregular connective tissue or loose connective tissue that supports the mucosa, as well as joins the mucosa to the bulk of underlying smooth muscle .-Contents:Blood vessels, lymphatic vessels, and nerves will run through...

 and thence the muscularis propria. Tumor cells describe irregular tubular structures, harboring pluristratification, multiple lumens, reduced stroma ("back to back" aspect). Sometimes, tumor cells are discohesive and secrete mucus, which invades the interstitium producing large pools of mucus/colloid (optically "empty" spaces) - mucinous (colloid) adenocarcinoma, poorly differentiated. If the mucus remains inside the tumor cell, it pushes the nucleus at the periphery - "signet-ring cell." Depending on glandular architecture, cellular pleomorphism, and mucosecretion of the predominant pattern, adenocarcinoma may present three degrees of differentiation: well, moderately, and poorly differentiated.

Most colorectal cancer tumors are thought to be cyclooxygenase-2 (COX-2) positive. This enzyme is generally not found in healthy colon tissue, but is thought to fuel abnormal cell growth.

Staging

Colon cancer staging
Cancer staging
The stage of a cancer is a description of the extent the cancer has spread. The stage often takes into account the size of a tumor, how deeply it has penetrated, whether it has invaded adjacent organs, how many lymph nodes it has metastasized to , and whether it has spread to distant organs...

 is an estimate of the amount of penetration of a particular cancer. It is performed for diagnostic and research purposes, and to determine the best method of treatment. The systems for staging colorectal cancers depend on the extent of local invasion, the degree of lymph node involvement and whether there is distant metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

.

Definitive staging can only be done after surgery
Colectomy
Colectomy consists of the surgical resection of any extent of the large intestine .-History:Sir William Arbuthnot-Lane was one of the early proponents of the usefulness of total colectomies, although his overuse of the procedure called the wisdom of the surgery into question.-Indications:Some of...

 has been performed and pathology reports reviewed. An exception to this principle would be after a colonoscopic polypectomy of a malignant pedunculated polyp with minimal invasion. Preoperative staging of rectal cancers may be done with endoscopic ultrasound
Endoscopic ultrasound
Endoscopic ultrasound or echo-endoscopy is a medical procedure in endoscopy is combined with ultrasound to obtain images of the internal organs in the chest and abdomen. It can be used to visualize the wall of these organs, or to look at adjacent structures...

. Adjunct staging of metastasis include Abdominal Ultrasound
Medical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...

, MRI
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...

, CT
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

, PET Scanning
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...

, and other imaging studies.

The most common staging system is the TNM (for tumors/nodes/metastases) system, from the American Joint Committee on Cancer
American Joint Committee on Cancer
The American Joint Committee on Cancer is an organization best known for defining and popularizing cancer staging standards, officially the AJCC staging system....

 (AJCC). The TNM system assigns a number based on three categories. "T" denotes the degree of invasion of the intestinal wall, "N" the degree of lymphatic node involvement, and "M" the degree of metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

. The broader stage of a cancer is usually quoted as a number I, II, III, IV derived from the TNM value grouped by prognosis; a higher number indicates a more advanced cancer and likely a worse outcome. Details of this system are in the graph below:
AJCC stage
AJCC staging system
The AJCC staging system is a classification system developed by the American Joint Committee on Cancer for describing the extent of disease progression in cancer patients....

TNM stage 2002 6th edition TNM stage criteria for colorectal cancer (superceded by 2010 7th edition)
Stage 0 Tis N0 M0 Tis: Tumor confined to mucosa; cancer-in-situ
Stage I T1 N0 M0 T1: Tumor invades submucosa
Submucosa
In the gastrointestinal tract, the submucosa is the layer of dense irregular connective tissue or loose connective tissue that supports the mucosa, as well as joins the mucosa to the bulk of underlying smooth muscle .-Contents:Blood vessels, lymphatic vessels, and nerves will run through...

Stage I T2 N0 M0 T2: Tumor invades muscularis propria
Stage II-A T3 N0 M0 T3: Tumor invades subserosa or beyond (without other organs involved)
Stage II-B T4 N0 M0 T4: Tumor invades adjacent organs or perforates the visceral peritoneum
Peritoneum
The peritoneum is the serous membrane that forms the lining of the abdominal cavity or the coelom — it covers most of the intra-abdominal organs — in amniotes and some invertebrates...

Stage III-A T1-2 N1 M0 N1: Metastasis to 1 to 3 regional lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

s. T1 or T2.
Stage III-B T3-4 N1 M0 N1: Metastasis to 1 to 3 regional lymph nodes. T3 or T4.
Stage III-C any T, N2 M0 N2: Metastasis to 4 or more regional lymph nodes. Any T.
Stage IV any T, any N, M1 M1: Distant metastases present. Any T, any N.

Dukes system

The Dukes classification
Dukes classification
In 1932 the British pathologist Cuthbert Dukes devised a famous classification system for colorectal cancer. Several different forms of the Dukes classification were developed...

 is an older and less complicated staging system, that predates the TNM system. It identified the stages as:
  • A - Tumour confined to the intestinal wall
  • B - Tumour invading through the intestinal wall
  • C - With lymph node(s) involvement (this is further subdivided into C1 lymph node involvement where the apical node is not involved and C2 where the apical lymph node is involved)
  • D - With distant metastasis

Astler-Coller

A: Tumor limited to mucosa; carcinoma in situ
B1: Tumor grows through muscularis mucosae but not through muscularis propria
B2: Tumor grows beyond muscularis propria
C1: Stage B1 with regional lymph node metastases
C2: Stage B2 with regional lymph node metastases
D: Distant metastases.

Additional Staging

venous invasion (v)
  • v0 no venous invasion
  • v1 microscopic venous invasion
  • v2 macroscopic venous invasion

lymphatic invasion (l)
  • l0 no lymphatic vessel invasion
  • l1 lymphatic vessel invasion

histologic grade (G)
  • g1 well differentiated
  • g2 moderately differentiated
  • g3 poorly differentiated
  • g4 undiffererentiated

Prevention

Most colorectal cancers should be preventable, through increased surveillance, improved lifestyle, and, probably, the use of dietary chemopreventative agents.

Surveillance

Most colorectal cancers arise from adenomatous polyps. These lesions can be detected and removed during colonoscopy. A 1993 study suggested this procedure would decrease by > 80% the risk of cancer death, provided it is started by the age of 50, and repeated every 5 or 10 years. A 2009 study published in the Annals of Internal Medicine implies that colonoscopy screening prevents approximately two thirds of the deaths due to colorectal cancers on the left side of the colon, and is not associated with a significant reduction in deaths from right-sided disease. The summary result suggested approximately a 37% reduction in net death rate from colorectal cancer.

As per current guidelines under National Comprehensive Cancer Network
National Comprehensive Cancer Network
National Comprehensive Cancer Network is an alliance of twenty-one cancer centers in the United States, most of which are designated by the National Cancer Institute as comprehensive cancer centers...

, in average risk individuals with negative family history of colon cancer and personal history negative for adenomas or inflammatory bowel diseases, flexible sigmoidoscopy every 5 years with fecal occult blood testing annually or double contrast barium enema are other options acceptable for screening rather than colonoscopy every 10 years (which is currently the "gold standard" of care).

Lifestyle and nutrition

The comparison of colorectal cancer incidence in various countries strongly suggests that sedentarity, overeating (i.e., high caloric intake), and perhaps a diet high in meat (red or processed) could increase the risk of colorectal cancer. In contrast, a healthy body weight, physical fitness, and good nutrition decreases cancer risk in general. Accordingly, lifestyle changes could decrease the risk of colorectal cancer as much as 60-80%.

A high intake of dietary fiber (from eating fruits, vegetables, cereals, and other high fiber food products) has, until recently, been thought to reduce the risk of colorectal cancer and adenoma. In the largest study ever to examine this theory (88,757 subjects tracked over 16 years), it has been found that a fiber rich diet does not reduce the risk of colon cancer. A 2005 meta-analysis study further supports these findings.

The Harvard School of Public Health states:
"Health Effects of Eating Fiber: Long heralded as part of a healthy diet, fiber appears to reduce the risk of developing various conditions, including heart disease, diabetes, diverticular disease, and constipation. Despite what many people may think, however, fiber probably has little, if any effect on colon cancer risk."

Physical Activity

Physical inactivity is a risk factor for developing colorectal cancer. The American Institute for Cancer Research (AICR) classifies the evidence for the role of physical activity in reducing the risk of developing colorectal cancer as “convincing.” The report goes on to recommend that people be physically active everyday and strive for attaining at least 30 minutes of physical activity with a recommendation of 30-60 minutes of moderate to vigorous activity daily.

The evidence supporting physical activity as prevention for colorectal cancer is deemed “surprisingly consistent” by the AICR. A meta-analysis of 19 cohort studies published in 2004 showed a statistically significant reduction in risk for physical activity and colon cancer. This effect was not seen for rectal cancer.

Chemoprevention

More than 200 agents, including the above cited phytochemicals, and other food components like calcium or folic acid (a B vitamin), and NSAIDs like aspirin, are able to decrease carcinogenesis in pre-clinical development
Pre-clinical development
In drug development, pre-clinical development is a stage of research that begins before clinical trials can begin, and during which important feasibility, iterative testing and drug safety data is collected....

 models: Some studies show full inhibition of carcinogen-induced tumours in the colon of rats. Other studies show strong inhibition of spontaneous intestinal polyps in mutated mice (Min mice). Chemoprevention clinical trials in human volunteers have shown smaller prevention, but few intervention studies have been completed today. The "chemoprevention database" shows the results of all published scientific studies of chemopreventive agents, in people and in animals.

Aspirin chemoprophylaxis

Aspirin should not be taken routinely to prevent colorectal cancer, even in people with a family history of the disease, because the risk of bleeding and kidney failure from high dose aspirin (300 mg or more) outweigh the possible benefits.

A clinical practice guideline of the U.S. Preventive Services Task Force (USPSTF) recommended against taking aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...

 (grade D recommendation). The Task Force acknowledged that aspirin may reduce the incidence of colorectal cancer, but "concluded that harms outweigh the benefits of aspirin and NSAID use for the prevention of colorectal cancer". A subsequent meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...

 concluded "300 mg or more of aspirin a day for about 5 years is effective in primary prevention of colorectal cancer in randomised controlled trials, with a latency of about 10 years". However, long-term doses over 81 mg per day may increase bleeding events.

Calcium

The meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...

 by the Cochrane Collaboration
Cochrane Collaboration
The Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...

 of randomized controlled trials published through 2002 concluded "Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps, this does not constitute sufficient evidence to recommend the general use of calcium supplements to prevent colorectal cancer." Subsequently, one randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...

 by the Women's Health Initiative
Women's Health Initiative
The Women's Health Initiative was initiated by the U.S. National Institutes of Health in 1991. The objective of this women's health research initiative was to conduct medical research into some of the major health problems of older women...

 (WHI) reported negative results. A second randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...

 reported reduction in all cancers, but had insufficient colorectal cancers for analysis.

Vitamin D

A scientific review undertaken by the National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...

 found that vitamin D was beneficial in preventing colorectal cancer, which showed an inverse relationship with blood levels of 80 nmol/L or higher associated with a 72% risk reduction compared with lower than 50 nmol/L. A possible mechanism is inhibition of Hedgehog signal transduction.

Management

The treatment depends on the stage of the cancer. When colorectal cancer is caught at early stages (with little spread), it can be curable. However, when it is detected at later stages (when distant metastases
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

 are present), it is less likely to be curable.

Surgery remains the primary treatment, while chemotherapy and/or radiotherapy may be recommended depending on the individual patient's staging and other medical factors.

Because colon cancer primarily affects the elderly, it can be a challenge to determine how aggressively to treat a particular patient, especially after surgery. Clinical trials suggest "otherwise fit" elderly patients fare well if they have adjuvant chemotherapy after surgery, so chronological age alone should not be a contraindication to aggressive management.

Surgery

Surgeries can be categorised into curative, palliative, bypass, fecal diversion, or open-and-close.

Curative surgical
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

 treatment can be offered if the tumor is localized.
  • Very early cancer that develops within a polyp
    Polyp
    A polyp in zoology is one of two forms found in the phylum Cnidaria, the other being the medusa. Polyps are approximately cylindrical in shape and elongated at the axis of the body...

     can often be cured by removing the polyp (i.e., polypectomy) at the time of colonoscopy
    Colonoscopy
    Colonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...

    .
  • In colon cancer, a more advanced tumor typically requires surgical removal of the section of colon containing the tumor with sufficient margins, and radical en-bloc resection of mesentery
    Mesentery
    In anatomy, the mesentery is the double layer of peritoneum that suspends the jejunum and ileum from the posterior wall of the abdomen. Its meaning, however, is frequently extended to include double layers of peritoneum connecting various components of the abdominal cavity.-Mesentery :The...

     and lymph node
    Lymph node
    A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

    s to reduce local recurrence (i.e., colectomy). If possible, the remaining parts of colon are anastomosed
    Anastomosis
    An anastomosis is the reconnection of two streams that previously branched out, such as blood vessels or leaf veins. The term is used in medicine, biology, mycology and geology....

     to create a functioning colon. In cases when anastomosis is not possible, a stoma
    Stoma (medicine)
    A stoma is an opening , either natural or surgically created, which connects a portion of the body cavity to the outside environment...

     (artificial orifice) is created.
  • Curative surgery on rectal cancer includes total mesorectal excision
    Total mesorectal excision
    Total mesorectal excision is a standard technique for treatment of colorectal cancer, devised some 20 years ago by Professor Bill Heald at the UK's Basingstoke District Hospital. A significant length of the bowel around the tumour is removed, and the removed lymph system scrutinised for cancerous...

     (lower anterior resection
    Lower anterior resection
    A lower anterior resection, formally known as anterior resection of the rectum and anterior excision of the rectum or simply anterior resection , is a common surgery for rectal cancer and occasionally is performed to remove a diseased or ruptured portion of the intestine in cases of diverticulitis...

    ) or abdominoperineal excision.


In case of multiple metastases, palliative (noncurative) resection
Segmental resection
Segmental resection is a surgical procedure to remove part of an organ or gland. It may also be used to remove a tumor and normal tissue around it. In lung cancer surgery, segmental resection refers to removing a section of a lobe of the lung.- External links :* entry in the public domain NCI...

 of the primary tumor is still offered to reduce further morbidity caused by tumor bleeding, invasion, and its catabolic effect. Surgical removal of isolated liver metastases is, however, common and may be curative in selected patients; improved chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

 has increased the number of patients who are offered surgical removal of isolated liver metastases.

If the tumor invaded into adjacent vital structures, which makes excision technically difficult, the surgeons may prefer to bypass the tumor (ileotransverse bypass) or to do a proximal fecal diversion through a stoma
Stoma (medicine)
A stoma is an opening , either natural or surgically created, which connects a portion of the body cavity to the outside environment...

.

Laparoscopic
Laparoscopic surgery
Laparoscopic surgery, also called minimally invasive surgery , bandaid surgery, or keyhole surgery, is a modern surgical technique in which operations in the abdomen are performed through small incisions as opposed to the larger incisions needed in laparotomy.Keyhole surgery makes use of images...

-assisted colectomy
Colectomy
Colectomy consists of the surgical resection of any extent of the large intestine .-History:Sir William Arbuthnot-Lane was one of the early proponents of the usefulness of total colectomies, although his overuse of the procedure called the wisdom of the surgery into question.-Indications:Some of...

 is a minimally invasive
Minimally invasive procedure
There are three main categories which describe the invasiveness of surgical procedures. These are: non-invasive procedures, minimally invasive procedures, and invasive procedures ....

 technique that can reduce the size of the incision and may reduce postoperative pain.

As with any surgical procedure, colorectal surgery may result in complications, including
  • wound infection
    Infection
    An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

    , dehiscence (bursting of wound) or hernia,
  • anastomosis breakdown, leading to abscess or fistula formation, and/or peritonitis,
  • bleeding with or without hematoma
    Hematoma
    A hematoma, or haematoma, is a localized collection of blood outside the blood vessels, usually in liquid form within the tissue. This distinguishes it from an ecchymosis, which is the spread of blood under the skin in a thin layer, commonly called a bruise...

     formation,
  • adhesions
    Adhesion (medicine)
    Adhesions are fibrous bands that form between tissues and organs, often as a result of injury during surgery. They may be thought of as internal scar tissue that connect tissues not normally connected.-Pathophysiology:...

     resulting in bowel obstruction
    Bowel obstruction
    Bowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...

    . A 5-year study of patients who had surgery in 1997 found the risk of hospital readmission to be 15% after panproctocolectomy, 9% after total colectomy, and 11% after ileostomy
    Ileostomy
    An ileostomy is a surgical opening constructed by bringing the end or loop of small intestine out onto the surface of the skin. Intestinal waste passes out of the ileostomy and is collected in an external pouching system stuck to the skin...

  • adjacent organ injury; most commonly to the small intestine, ureters, spleen, or bladder.
  • cardiorespiratory complications, such as myocardial infarction
    Myocardial infarction
    Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

    , pneumonia
    Pneumonia
    Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

    , arrythmia, pulmonary embolism
    Pulmonary embolism
    Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...

    , etc.

Chemotherapy

Chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

 is used to reduce the likelihood of metastasis developing, shrink tumor size, or slow tumor growth. Chemotherapy is often applied after surgery (adjuvant), before surgery (neoadjuvant), or as the primary therapy (palliative). The treatments listed here have been shown in clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

s to improve survival and/or reduce mortality rate, and have been approved for use by the US Food and Drug Administration. In colon cancer, chemotherapy after surgery is usually only given if the cancer has spread to the lymph nodes(Stage III).
  • Adjuvant (after surgery) chemotherapy
    • 5-fluorouracil (5-FU) or capecitabine (Xeloda)
    • Leucovorin (LV, folinic Acid)
    • Oxaliplatin
      Oxaliplatin
      Oxaliplatin is a coordination complex that is used in cancer chemotherapy. These platinum-based drugs are usually classified as alkylating agents, although they are not actually alkylating groups ....

       (Eloxatin)

  • Chemotherapy for metastatic disease. Commonly used first line chemotherapy regimens involve the combination of infusional 5-fluorouracil, leucovorin, and oxaliplatin
    Oxaliplatin
    Oxaliplatin is a coordination complex that is used in cancer chemotherapy. These platinum-based drugs are usually classified as alkylating agents, although they are not actually alkylating groups ....

     (FOLFOX
    FOLFOX
    FOLFOX is a chemotherapy regimen for treatment of colorectal cancer, made up of the drugs* FOL– Folinic acid * F – Fluorouracil * OX – Oxaliplatin - FOLFOX4 :...

    ) with bevacizumab
    Bevacizumab
    Bevacizumab is a drug that blocks angiogenesis, the growth of new blood vessels. It is commonly used to treat various cancers, including colorectal, lung, breast, kidney, and glioblastomas....

     or infusional 5-fluorouracil, leucovorin, and irinotecan
    Irinotecan
    Irinotecan is a drug used for the treatment of cancer.Irinotecan prevents DNA from unwinding by inhibition of topoisomerase 1. In chemical terms, it is a semisynthetic analogue of the natural alkaloid camptothecin....

     (FOLFIRI
    FOLFIRI
    FOLFIRI is a chemotherapy regimen for treatment of colorectal cancer. It is made up of the following drugs:* FOL – folinic acid , a vitamin B derivative used as a "rescue" drug for high doses of the drug methotrexate and that modulates/potentiates/reduces the side effects of fluorouracil;* F – ...

    ) with bevacizumab
    Bevacizumab
    Bevacizumab is a drug that blocks angiogenesis, the growth of new blood vessels. It is commonly used to treat various cancers, including colorectal, lung, breast, kidney, and glioblastomas....

     or the same chemotherapy drug combinations with cetuximab in KRAS wild type tumors
    • 5-fluorouracil (5-FU)
    • capecitabine (Xeloda)
    • UFT
      Tegafur-uracil
      Tegafur-uracil is a chemotherapy drug used in the treatment of cancer, primarily bowel cancer. It is also called UFT or UFUR.-Development and regulation:...

       or Tegafur-uracil
    • Leucovorin (LV, folinic Acid)
    • Irinotecan
      Irinotecan
      Irinotecan is a drug used for the treatment of cancer.Irinotecan prevents DNA from unwinding by inhibition of topoisomerase 1. In chemical terms, it is a semisynthetic analogue of the natural alkaloid camptothecin....

       (Camptosar)
    • Oxaliplatin
      Oxaliplatin
      Oxaliplatin is a coordination complex that is used in cancer chemotherapy. These platinum-based drugs are usually classified as alkylating agents, although they are not actually alkylating groups ....

       (Eloxatin)
    • Gemcitabine (Gemzar)
    • Bevacizumab
      Bevacizumab
      Bevacizumab is a drug that blocks angiogenesis, the growth of new blood vessels. It is commonly used to treat various cancers, including colorectal, lung, breast, kidney, and glioblastomas....

       (Avastin)
    • Cetuximab
      Cetuximab
      Cetuximab is a chimeric monoclonal antibody, an epidermal growth factor receptor inhibitor, given by intravenous infusion for treatment of metastatic colorectal cancer and head and neck cancer.- Distribution :Cetuximab is manufactured and distributed in North America by ImClone and Bristol-Myers...

       (Erbitux)
    • Panitumumab
      Panitumumab
      Panitumumab , formerly ABX-EGF, is a fully human monoclonal antibody specific to the epidermal growth factor receptor ....

       (Vectibix)

  • In clinical trials for treated/untreated metastatic disease.
    • Bortezomib
      Bortezomib
      Bortezomib is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma...

       (Velcade)
    • Oblimersen
      Oblimersen
      Oblimersen is an antisense oligodeoxyribonucleotide being studied as a possible treatment for several types of cancer, including chronic lymphocytic leukemia, B-cell lymphoma, and breast cancer...

       (Genasense, G3139)
    • Gefitinib
      Gefitinib
      Gefitinib INN , trade name Iressa, is a drug used in the treatment of certain types of cancer, particularly those with mutated and overactive EGFR. Gefitinib is an EGFR inhibitor, like erlotinib, which interrupts signaling through the epidermal growth factor receptor in target cells...

       and erlotinib
      Erlotinib
      Erlotinib hydrochloride is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. It is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor . It is marketed in the United States by Genentech and OSI...

       (Tarceva)
    • Topotecan
      Topotecan
      Topotecan hydrochloride is a chemotherapy agent that is a topoisomerase I inhibitor. It is the water-soluble derivative of camptothecin...

       (Hycamtin)


At the 2008 annual meeting of the American Society of Clinical Oncology, researchers announced that colorectal cancer patients that have a mutation in the KRAS gene do not respond to certain therapies, those that inhibit the epidermal growth factor receptor
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...

 (EGFR)--namely Erbitux (cetuximab
Cetuximab
Cetuximab is a chimeric monoclonal antibody, an epidermal growth factor receptor inhibitor, given by intravenous infusion for treatment of metastatic colorectal cancer and head and neck cancer.- Distribution :Cetuximab is manufactured and distributed in North America by ImClone and Bristol-Myers...

) and Vectibix (panitumumab
Panitumumab
Panitumumab , formerly ABX-EGF, is a fully human monoclonal antibody specific to the epidermal growth factor receptor ....

). Following recommendations by ASCO, patients should now be tested for the KRAS gene mutation before being offered these EGFR-inhibiting drugs. In July 2009, the US Food and Drug Administration (FDA) updated the labels of two anti-EGFR monoclonal antibody drugs (panitumumab
Panitumumab
Panitumumab , formerly ABX-EGF, is a fully human monoclonal antibody specific to the epidermal growth factor receptor ....

 (Vectibix) and cetuximab
Cetuximab
Cetuximab is a chimeric monoclonal antibody, an epidermal growth factor receptor inhibitor, given by intravenous infusion for treatment of metastatic colorectal cancer and head and neck cancer.- Distribution :Cetuximab is manufactured and distributed in North America by ImClone and Bristol-Myers...

 (Erbitux)) indicated for treatment of metastatic colorectal cancer to include information about KRAS mutations.

However, having the normal KRAS version does not guarantee these drugs will benefit the patient.
“The trouble with the KRAS mutation is that it’s downstream of EGFR,” says Richard Goldberg, MD, director of oncology at the Lineberger Comprehensive Cancer Center at the University of North Carolina. “It doesn’t matter if you plug the socket if there’s a short downstream of the plug. The mutation turns [EGFR] into a switch that’s always on.” But this doesn’t mean that having normal, or wild-type, KRAS is a fail-safe. “It isn’t foolproof,” cautions Goldberg. “If you have wild-type KRAS, you’re more likely to respond, but it’s not a guarantee.” Tumors shrink in response to these drugs in up to 40 percent of patients with wild-type KRAS, and progression-free and overall survival is increased.

The cost benefit of testing patients for the KRAS gene could potentially save about $740 million a year by not providing EGFR-inhibiting drugs to patients who would not benefit from the drugs. "With the assumption that patients with mutated Kras (35.6% of all patients) would not receive cetuximab (other studies have found Kras mutation in up to 46% of patients), theoretical drug cost savings would be $753 million; considering the cost of Kras testing, net savings would be $740 million."

Radiation therapy

Radiotherapy is not used routinely in colon cancer, as normal cells in the bowel lining are also rapidly reproducing and can thus have their vitality and reproduction affected by the radiation just as the cancer cells are, a condition called radiation enteritis. It is also difficult to target specific portions of the colon. It is more common for radiation to be used in rectal cancer, since the rectum does not move as much as the colon and is thus easier to target. Indications include:
  • Colon cancer
    • pain relief and palliation - targeted at metastatic
      Metastasis
      Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

       tumor deposits if they compress vital structures and/or cause pain
  • Rectal cancer
    • neoadjuvant - given before surgery in patients with tumors that extend outside the rectum or have spread to regional lymph nodes, to decrease the risk of recurrence following surgery or to allow for less invasive surgical approaches (such as a low anterior resection instead of an abdominoperineal resection). In locally advanced adenocarcinoma of middle and lower rectum, regional hyperthermia added to chemoradiotherapy achieved good results in terms of rate of sphincter-sparing surgery.

    • adjuvant - where a tumor perforates the rectum or involves regional lymph nodes (AJCC T3 or T4 tumors or Duke's B or C tumors)
    • palliative - to decrease the tumor burden to relieve or prevent symptoms


Sometimes chemotherapy agents are used to increase the effectiveness of radiation by sensitizing tumor cells, if present.

Immunotherapy

Bacillus Calmette-Guérin
Bacillus Calmette-Guérin
Bacillus Calmette-Guérin is a vaccine against tuberculosis that is prepared from a strain of the attenuated live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans by being specially subcultured in an artificial medium for 13 years, and also prepared from...

 (BCG) is being investigated as an adjuvant mixed with autologous tumor cells in immunotherapy for colorectal cancer.

Cancer Vaccine

TroVax
TroVax
TroVax is a cancer vaccine being developed by Oxford BioMedica. No cancer vaccines have been proven to cure cancer or extend life yet, but TroVax is recruiting patients for 3 human trials.TroVax uses a tumor-associated antigen, 5T4, with a pox virus vector...

, a cancer vaccine
Cancer vaccine
The term cancer vaccine refers to a vaccine that either prevents infections with cancer-causing viruses, treats existing cancer or prevents the development of cancer in certain high risk individuals...

, produced by Oxford BioMedica
Oxford BioMedica
Oxford BioMedica is a biopharmaceutical company specializing in the development and commercialization of innovative gene-based medicines. It was established in 1995 as a spin out from Oxford University. The lead product is TroVax, a therapeutic cancer vaccine for multiple solid cancers, which is...

, is in Phase III trials for renal cancers, and Phase III trials are planned for colon cancers.

Treatment of liver metastases

According to the American Cancer Society statistics in 2006, over 20% of patients present with metastatic (stage IV) colorectal cancer at the time of diagnosis, and up to 25% of this group will have isolated liver metastasis that is potentially resectable. Lesions which undergo curative resection have demonstrated 5-year survival outcomes now exceeding 50%.

Resectability of a liver metastasis is determined using preoperative imaging studies (CT or MRI), intraoperative ultrasound, and by direct palpation and visualization during resection. Lesions confined to the right lobe are amenable to en bloc removal with a right hepatectomy (liver resection) surgery. Smaller lesions of the central or left liver lobe may sometimes be resected in anatomic "segments", while large lesions of left hepatic lobe are resected by a procedure called hepatic trisegmentectomy. Treatment of lesions by smaller, nonanatomic "wedge" resections is associated with higher recurrence rates. Some lesions which are not initially amenable to surgical resection may become candidates if they have significant responses to preoperative chemotherapy or immunotherapy regimens. Lesions which are not amenable to surgical resection for cure can be treated with modalities including radio-frequency ablation (RFA), cryoablation, and chemoembolization.

Patients with colon cancer and metastatic disease to the liver may be treated in either a single surgery or in staged surgeries (with the colon tumor traditionally removed first) depending upon the fitness of the patient for prolonged surgery, the difficulty expected with the procedure with either the colon or liver resection, and the comfort of the surgery performing potentially complex hepatic surgery.

Aspirin

A study published in 2009 found that aspirin reduces risk of colorectal neoplasia
Neoplasia
Neoplasm is an abnormal mass of tissue as a result of neoplasia. Neoplasia is the abnormal proliferation of cells. The growth of neoplastic cells exceeds and is not coordinated with that of the normal tissues around it. The growth persists in the same excessive manner even after cessation of the...

 in randomized trials, and inhibits tumor growth and metastases in animal models. The influence of aspirin on survival after diagnosis of colorectal cancer is unknown. Several reports, including a prospective cohort of 1,279 people diagnosed with stages I-III (nonmetastatic) colorectal cancer, have suggested a significant improvement in cancer-specific survival in a subset of patients using aspirin.

Cimetidine

Cimetidine
Cimetidine
Cimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...

 is being investigated in Japan as an adjuvant for adenocarcinomas, including for stage III and stage IV colorectal cancers biomarked with overexpressed sialyl Lewis X and A epitopes. Multiple small trials suggest a significant survival improvement in the subset of patients with the sLeX and sLeA biomarkers that take cimetidine treatment perioperatively, through several mechanisms http://molpharm.aspetjournals.org/content/70/2/450.full.pdf.

Support therapies

Cancer diagnosis very often results in an enormous change in the patient's psychological well-being. Various support resources are available from hospitals and other agencies, which provide counseling, social service support, cancer support group
Cancer support group
Cancer support groups provide a setting in which cancer patients can talk about living with cancer with others who may be having similar experiences...

s, and other services. These services help to mitigate some of the difficulties of integrating patients' medical complications into other parts of their lives.

Palliative care

In patients with incurable colorectal cancer, palliative care
Palliative care
Palliative care is a specialized area of healthcare that focuses on relieving and preventing the suffering of patients...

 can be considered for improving the patients symptom management and quality of life. Surgical options for treatment of symptoms include non-curative surgical resection of tumor, fecal diversion, and endoluminal laser surgery or stent placement. These procedures can be considered to alleviate symptoms and complications such as anemia from bleeding from the tumor, abdominal pain and intestinal obstruction. Non-operative methods of symptomatic treatment include external beam or intraoperative radiation therapy for managing pain and tumor size as well as analgesic medications, including intrathetcal pain medication when necessary.

Prognosis

Survival is directly related to detection and the type of cancer involved, but overall is poor for symptomatic cancers, as they are typically quite advanced. Survival rates for early stage detection is about 5 times that of late stage cancers. For example, patients with a tumor that has not breached the muscularis mucosa (TNM stage Tis, N0, M0) have an average 5-year survival of 100%, while those with an invasive cancer, i.e. T1 (within the submucosal layer) or T2 (within the muscular layer) cancer have an average 5-year survival of approximately 90%. Those with a more invasive tumor, yet without node involvement (T3-4, N0, M0) have an average 5-year survival of approximately 70%. Patients with positive regional lymph nodes (any T, N1-3, M0) have an average 5-year survival of approximately 40%, while those with distant metastases (any T, any N, M1) have an average 5-year survival of approximately 5%.

CEA level is also directly related to the prognosis of disease, since its level correlates with the bulk of tumor tissue.

Follow-up

The aims of follow-up are to diagnose, in the earliest possible stage, any metastasis or tumors that develop later, but did not originate from the original cancer (metachronous lesions).

The U.S. National Comprehensive Cancer Network
National Comprehensive Cancer Network
National Comprehensive Cancer Network is an alliance of twenty-one cancer centers in the United States, most of which are designated by the National Cancer Institute as comprehensive cancer centers...

 and American Society of Clinical Oncology
American Society of Clinical Oncology
The American Society of Clinical Oncology is the world's leading professional organization representing physicians of all oncology subspecialties who care for people with cancer. Founded in 1964 by Drs...

 provide guidelines for the follow-up of colon cancer. A medical history
Medical history
The medical history or anamnesis of a patient is information gained by a physician by asking specific questions, either of the patient or of other people who know the person and can give suitable information , with the aim of obtaining information useful in formulating a diagnosis and providing...

 and physical examination
Physical examination
Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...

 are recommended every 3 to 6 months for 2 years, then every 6 months for 5 years. Carcinoembryonic antigen
Carcinoembryonic antigen
Carcinoembryonic antigen is a glycoprotein involved in cell adhesion. It is normally produced during fetal development, but the production of CEA stops before birth. Therefore, it is not usually present in the blood of healthy adults, although levels are raised in heavy smokers...

 blood level measurements follow the same timing, but are only advised for patients with T2 or greater lesions who are candidates for intervention. A CT-scan
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

 of the chest, abdomen and pelvis can be considered annually for the first 3 years for patients who are at high risk of recurrence (for example, patients who had poorly differentiated tumors or venous or lymphatic invasion) and are candidates for curative surgery (with the aim to cure). A colonoscopy
Colonoscopy
Colonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...

 can be done after 1 year, except if it could not be done during the initial staging because of an obstructing mass, in which case it should be performed after 3 to 6 months. If a villous polyp, a polyp >1 centimeter or high grade dysplasia is found, it can be repeated after 3 years, then every 5 years. For other abnormalities, the colonoscopy can be repeated after 1 year.

Routine PET
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...

 or ultrasound scanning
Medical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...

, chest X-ray
Chest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...

s, complete blood count
Complete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...

 or liver function tests
Liver function tests
Liver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...

 are not recommended. These guidelines are based on recent meta-analyses showing intensive surveillance and close follow-up can reduce the 5-year mortality rate from 37% to 30%.

Epidemiology

The incidence of colorectal cancer varies greatly between different regions of the world, much of it can be attributed to differences in diet, particularly the consumption of red and processed meat, fibre and alcohol, as well as bodyweight and physical activity.

Incidence rates of colorectal cancer are increasing in countries where rates were previously low (especially in Japan, but also in other Asian countries) as diets become more Westernised, and either gradually increasing, stabilising (Northern and Western Europe) or declining (North America) with time. In 2008, almost 60% of cases were diagnosed in the developed world.

Notable patients

  • Corazon Aquino
    Corazon Aquino
    Maria Corazon Sumulong Cojuangco-Aquino was the 11th President of the Philippines and the first woman to hold that office in Philippine history. She is best remembered for leading the 1986 People Power Revolution, which toppled Ferdinand Marcos and restored democracy in the Philippines...

    , former president
    President of the Philippines
    The President of the Philippines is the head of state and head of government of the Philippines. The president leads the executive branch of the Philippine government and is the commander-in-chief of the Armed Forces of the Philippines...

     of the Philippines
    Philippines
    The Philippines , officially known as the Republic of the Philippines , is a country in Southeast Asia in the western Pacific Ocean. To its north across the Luzon Strait lies Taiwan. West across the South China Sea sits Vietnam...

  • Pope John Paul II
    Pope John Paul II
    Blessed Pope John Paul II , born Karol Józef Wojtyła , reigned as Pope of the Catholic Church and Sovereign of Vatican City from 16 October 1978 until his death on 2 April 2005, at of age. His was the second-longest documented pontificate, which lasted ; only Pope Pius IX ...

  • Ronald Reagan
    Ronald Reagan
    Ronald Wilson Reagan was the 40th President of the United States , the 33rd Governor of California and, prior to that, a radio, film and television actor....

  • Harold Wilson
    Harold Wilson
    James Harold Wilson, Baron Wilson of Rievaulx, KG, OBE, FRS, FSS, PC was a British Labour Member of Parliament, Leader of the Labour Party. He was twice Prime Minister of the United Kingdom during the 1960s and 1970s, winning four general elections, including a minority government after the...

    , former Prime Minister
    Prime minister
    A prime minister is the most senior minister of cabinet in the executive branch of government in a parliamentary system. In many systems, the prime minister selects and may dismiss other members of the cabinet, and allocates posts to members within the government. In most systems, the prime...

     of the United Kingdom
    United Kingdom
    The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...


See also

  • Diet and cancer
    Diet and cancer
    Diet and cancer are associated. While it is not yet possible to provide quantitative estimates of the overall risks, it has been estimated that 35 percent of cancer deaths may be related to dietary factors. Almost all cancers are caused by environmental factors, and of these, 30–40% of cancers are...

  • Bowel & Cancer Research
    Bowel & Cancer Research
    Bowel & Cancer Research is a registered charity based in the United Kingdom.It is an organisation with three principal aims. The first is to improve survival rates for bowel cancer sufferers through research into the spread and behaviour of cancer in specific patient populations...

  • Mouse models of colorectal and intestinal cancer
    Mouse models of colorectal and intestinal cancer
    Mouse models of colorectal cancer and intestinal cancer are experimental systems in which mice are genetically manipulated or challenged with chemicals to develop malignancies in the gastrointestinal tract...


External links

  • American Cancer Society's Detailed Guide: Colon and Rectum Cancer
  • Clinically reviewed bowel cancer information for patients, from Cancer Research UK
    Cancer Research UK
    Cancer Research UK is a cancer research and awareness charity in the United Kingdom, formed on 4 February 2002 by the merger of The Cancer Research Campaign and the Imperial Cancer Research Fund. Its aim is to reduce the number of deaths from cancer. As the world's largest independent cancer...

  • UK bowel cancer statistics from Cancer Research UK
    Cancer Research UK
    Cancer Research UK is a cancer research and awareness charity in the United Kingdom, formed on 4 February 2002 by the merger of The Cancer Research Campaign and the Imperial Cancer Research Fund. Its aim is to reduce the number of deaths from cancer. As the world's largest independent cancer...

  • ColonCancerCheck including fact sheets in 24 languages at Ontario Ministry of Health and Long-Term Care
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