Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
from the
colon or
rectum
The rectum is the final straight portion of the large intestine in humans and some other mammals, and the Gastrointestinal tract, gut in others. The adult human rectum is about long, and begins at the rectosigmoid junction (the end of the s ...
(parts of the
large intestine
The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being r ...
).
Signs and symptoms may include
blood in the stool
Blood in stool looks different depending on how early it enters the digestive tract—and thus how much digestive action it has been exposed to—and how much there is. The term can refer either to melena, with a black appearance, typically orig ...
, a change in
bowel movements
Defecation (or defaecation) follows digestion, and is a necessary process by which organisms eliminate a solid, semisolid, or liquid waste material known as feces from the digestive tract via the anus. The act has a variety of names ranging f ...
, weight loss, and fatigue. Most colorectal cancers are due to old age and lifestyle factors, with only a small number of cases due to underlying
genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
s.
Risk factors include diet,
obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
, smoking, and lack of
physical activity
Physical activity is defined as any voluntary bodily movement produced by skeletal muscles that requires energy expenditure.Global Recommendations on Physical Activity for Health, 2009. World Health Organization. Geneva, Switzerland. Accessed 13/ ...
.
Dietary factors that increase the risk include
red meat
In gastronomy, red meat is commonly red when raw and a dark color after it is cooked, in contrast to white meat, which is pale in color before and after cooking. In culinary terms, only flesh from mammals or fowl (not fish) is classified as ...
,
processed meat
Processed meat is considered to be any meat which has been modified in order to either improve its taste or to extend its shelf life. Methods of meat processing include salting, curing, fermentation, smoking, and/or the addition of chemical pre ...
, and alcohol.
Another risk factor is
inflammatory bowel disease
Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...
, which includes
Crohn's disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...
and
ulcerative colitis
Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and a ...
.
Some of the inherited genetic disorders that can cause colorectal cancer include
familial adenomatous polyposis
Familial adenomatous polyposis (FAP) is an autosomal dominant inherited condition in which numerous Adenomatous polyps, adenomatous Colorectal polyp, polyps form mainly in the epithelium of the colon (anatomy), large intestine. While these polyps s ...
and
hereditary non-polyposis colon cancer
Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that is associated with a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ovar ...
; however, these represent less than 5% of cases.
It typically starts as a
benign tumor
A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize (spread throughout the body). Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have re ...
, often in the form of a
polyp, which over time becomes
cancerous
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Poss ...
.
Colorectal cancer may be diagnosed by
obtaining a sample of the colon during a
sigmoidoscopy
Sigmoidoscopy (from the Greek term for letter " s/ς" + "eidos" + "scopy": namely, to look inside an "s"/"ς"-like object) is the minimally invasive medical examination of the large intestine from the rectum through to the nearest part of the co ...
or
colonoscopy
Colonoscopy () or coloscopy () 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 can provide a visual diagnosis (''e. ...
.
This is then followed by
medical imaging
Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to rev ...
to determine whether the disease has spread.
Screening
Screening may refer to:
* Screening cultures, a type a medical test that is done to find an infection
* Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees)
* Screening (environmental), a ...
is effective for preventing and decreasing deaths from colorectal cancer.
Screening, by one of a number of methods, is recommended starting from the age of 50 to 75.
During colonoscopy, small polyps may be removed if found.
If a large polyp or tumor is found, a
biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
may be performed to check if it is cancerous.
Aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
and other
non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
decrease the risk of pain during polyp excision.
Their general use is not recommended for this purpose, however, due to side effects.
Treatments used for colorectal cancer may include some combination of surgery,
radiation therapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
,
chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
, and
targeted therapy
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks ...
.
[ Cancers that are confined within the wall of the colon may be curable with surgery, while cancer that has spread widely is usually not curable, with management being directed towards improving ]quality of life
Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...
and symptoms.[ The ]five-year survival rate
The five-year survival rate is a type of survival rate for estimating the prognosis of a particular disease, normally calculated from the point of diagnosis. Lead time bias from earlier diagnosis can affect interpretation of the five-year surviva ...
in the United States was around 65% in 2014. The individual likelihood of survival depends on how advanced the cancer is, whether or not all the cancer can be removed with surgery, and the person's overall health.[ Globally, colorectal cancer is the third most common type of cancer, making up about 10% of all cases.] In 2018, there were 1.09 million new cases and 551,000 deaths from the disease. It is more common in developed countries
A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state that has a high quality of life, developed economy and advanced technological infrastruct ...
, where more than 65% of cases are found. It is less common in women than men.
Signs and symptoms
The signs and symptoms of colorectal cancer depend on the location of the tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
in the bowel
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
, and whether it has spread elsewhere in the body (metastasis
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
). The classic warning signs include: worsening constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
, blood in the stool, decrease in stool caliber (thickness), loss of appetite, loss of weight, and nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
or vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose.
Vomiting can be the result of ailments like Food-poisoning, foo ...
in someone over 50 years old. Around 50% of individuals with colorectal cancer do not report any symptoms.
Rectal bleeding or anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
are high-risk symptoms in people over the age of 50. Weight loss and changes in a person's bowel habit are typically only concerning if they are associated with rectal bleeding.
Cause
75–95% of colorectal cancer cases occur in people with little or no genetic risk. Risk factors include older age, male sex,[ high intake of fat, ]sugar
Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or double ...
, alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
, red meat
In gastronomy, red meat is commonly red when raw and a dark color after it is cooked, in contrast to white meat, which is pale in color before and after cooking. In culinary terms, only flesh from mammals or fowl (not fish) is classified as ...
, processed meat
Processed meat is considered to be any meat which has been modified in order to either improve its taste or to extend its shelf life. Methods of meat processing include salting, curing, fermentation, smoking, and/or the addition of chemical pre ...
s, obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
, smoking
Smoking is a practice in which a substance is burned and the resulting smoke is typically breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have bee ...
, and a lack of physical exercise
Exercise is a body activity that enhances or maintains physical fitness and overall health and wellness.
It is performed for various reasons, to aid growth and improve strength, develop muscles and the cardiovascular system, hone athletic ...
. Approximately 10% of cases are linked to insufficient activity. The risk from alcohol appears to increase at greater than one drink per day. Drinking five glasses of water a day is linked to a decrease in the risk of colorectal cancer and adenomatous
An adenoma is a benign tumor of epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organs, including the adrenal glands, pituitary gland, thyroid, prostate, and others. Some adenomas ...
polyps. ''Streptococcus gallolyticus
''Streptococcus'' is a genus of gram-positive ' (plural ) or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell division in streptococci occurs ...
'' is associated with colorectal cancer. Some strains of ''Streptococcus bovis/Streptococcus equinus'' complex are consumed by millions of people daily and thus may be safe. 25 to 80% of people with ''Streptococcus bovis/gallolyticus'' bacteremia have concomitant colorectal tumors. Seroprevalence of ''Streptococcus bovis/gallolyticus'' is considered as a candidate practical marker for the early prediction of an underlying bowel lesion at high risk population.[ It has been suggested that the presence of antibodies to ''Streptococcus bovis/gallolyticus'' antigens or the antigens themselves in the bloodstream may act as markers for the carcinogenesis in the colon.][
Pathogenic ''Escherichia coli'' may increase the risk of colorectal cancer by producing the ]genotoxic Genotoxicity is the property of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with Mutagen, mutagenicity, all mutagens are genotoxic, but some geno ...
metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
, colibactin
Colibactin is a Genotoxicity, genotoxic metabolite produced by ''Escherichia coli'' and other ''Enterobacteriaceae'' ("enteric bacteria") believed to cause mutations leading to colorectal cancer and the progression of colorectal cancer. Colibactin ...
.
Inflammatory bowel disease
People with inflammatory bowel disease
Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...
(ulcerative colitis
Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and a ...
and Crohn's disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...
) are at increased risk of colon cancer. The risk increases the longer a person has the disease, and the worse the severity of inflammation. In these high risk groups, both prevention with aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
and regular colonoscopies
Colonoscopy () or coloscopy () 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 can provide a visual diagnosis (''e.g ...
are recommended. Endoscopic
An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are insert ...
surveillance in this high-risk population may reduce the development of colorectal cancer through early diagnosis and may also reduce the chances of dying from colon cancer. People with inflammatory bowel disease account for less than 2% of colon cancer cases yearly.[ In those with Crohn's disease, 2% get colorectal cancer after 10 years, 8% after 20 years, and 18% after 30 years.][ In people who have ulcerative colitis, approximately 16% develop either a cancer precursor or cancer of the colon over 30 years.][
]
Genetics
Those with a family history in two or more first-degree relatives (such as a parent or sibling) have a two to threefold greater risk of disease, and this group accounts for about 20% of all cases. A number of genetic syndromes are also associated with higher rates of colorectal cancer. The most common of these is hereditary nonpolyposis colorectal cancer
Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that is associated with a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ovary, ...
(HNPCC, or Lynch syndrome) which is present in about 3% of people with colorectal cancer.[ Other syndromes that are strongly associated with colorectal cancer include ]Gardner syndrome
Gardner's syndrome (also known as Gardner syndrome, familial polyposis of the colon, or familial colorectal polyposis) is a subtype of familial adenomatous polyposis (FAP). Gardner syndrome is an autosomal dominant form of polyposis characterize ...
and familial adenomatous polyposis
Familial adenomatous polyposis (FAP) is an autosomal dominant inherited condition in which numerous Adenomatous polyps, adenomatous Colorectal polyp, polyps form mainly in the epithelium of the colon (anatomy), large intestine. While these polyps s ...
(FAP). For people with these syndromes, cancer almost always occurs and makes up 1% of the cancer cases. A total proctocolectomy
Proctocolectomy is the surgical removal of the rectum and all or part of the colon. It is the most widely accepted surgical method for ulcerative colitis and familial adenomatous polyposis (FAP).
A proctocolectomy is considered a cure for ulcerat ...
may be recommended for people with FAP as a preventive measure due to the high risk of malignancy. Colectomy, removal of the colon, may not suffice as a preventive measure because of the high risk of rectal cancer if the rectum remains. The most common polyposis syndrome affecting the colon is serrated polyposis syndrome
Serrated polyposis syndrome (SPS), previously known as hyperplastic polyposis syndrome, is a disorder characterized by the appearance of serrated polyps in the colon. While serrated polyposis syndrome does not cause symptoms, the condition is assoc ...
, which is associated with a 25-40% risk of CRC.
Mutations in the pair of genes (POLE
Pole may refer to:
Astronomy
*Celestial pole, the projection of the planet Earth's axis of rotation onto the celestial sphere; also applies to the axis of rotation of other planets
*Pole star, a visible star that is approximately aligned with the ...
and POLD1
The gene polymerase delta 1 (''POLD1'') encodes the large, POLD1/p125, catalytic subunit of the DNA polymerase delta (Polδ) complex. The Polδ enzyme is responsible for synthesizing the lagging strand of DNA, and has also been implicated in some ...
) have been associated with familial colon cancer.
Most deaths due to colon cancer are associated with metastatic disease. A gene that appears to contribute to the potential for metastatic disease, metastasis associated in colon cancer 1 (''MACC1''), has been isolated. It is a transcriptional factor that influences the expression of hepatocyte growth factor
Hepatocyte growth factor (HGF) or scatter factor (SF) is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts o ...
. This gene is associated with the proliferation, invasion, and scattering of colon cancer cells in cell culture
Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This te ...
, and tumor growth and metastasis in mice. MACC1 may be a potential target for cancer intervention, but this possibility needs to be confirmed with clinical studies.[Stein U (2013) MACC1 – a novel target for solid cancers. Expert Opin Ther Targets]
Epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
factors, such as abnormal DNA methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
of tumor suppressor
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or red ...
promoters, play a role in the development of colorectal cancer.
Ashkenazi Jews
Ashkenazi Jews ( ; he, יְהוּדֵי אַשְׁכְּנַז, translit=Yehudei Ashkenaz, ; yi, אַשכּנזישע ייִדן, Ashkenazishe Yidn), also known as Ashkenazic Jews or ''Ashkenazim'',, Ashkenazi Hebrew pronunciation: , singu ...
have a 6% higher risk rate of getting adenoma
An adenoma is a benign tumor of epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organs, including the adrenal glands, pituitary gland, thyroid, prostate, and others. Some adenom ...
s and then colon cancer due to mutations in the APC gene
Adenomatous polyposis coli (APC) also known as deleted in polyposis 2.5 (DP2.5) is a protein that in humans is encoded by the ''APC'' gene. The APC protein is a negative regulator that controls beta-catenin concentrations and interacts with E-c ...
being more common.
Pathogenesis
Colorectal cancer is a disease originating from the epithelial cells
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
lining the colon or rectum of the gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
, most frequently as a result of mutations in the Wnt signaling pathway
The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling p ...
that increase signaling activity. The mutations can be inherited or acquired, and most probably occur in the intestinal crypt stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
. The most commonly mutated gene in all colorectal cancer is the '' APC'' gene, which produces the APC protein. The APC protein prevents the accumulation of β-catenin
Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcriptio ...
protein. Without APC, β-catenin
Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcriptio ...
accumulates to high levels and translocates (moves) into the nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
*Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucle ...
, binds to DNA, and activates the transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
of proto-oncogenes
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels. . These genes are normally important for stem cell renewal and differentiation, but when inappropriately expressed at high levels, they 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 own breakdown, or have mutations in other genes with function similar to APC such as AXIN1
Axin-1 is a protein that in humans is encoded by the ''AXIN1'' gene.
Function
This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded prote ...
, AXIN2
Axin-2 also known as axin-like protein (Axil) or axis inhibition protein 2 (AXIN2) or conductin is a protein that in humans is encoded by the ''AXIN2'' gene.
Function
The Axin-related protein, Axin2, presumably plays an important role in the r ...
, TCF7L2
Transcription factor 7-like 2 (T-cell specific, HMG-box), also known as TCF7L2 or TCF4, is a protein acting as a transcription factor that, in humans, is encoded by the ''TCF7L2'' gene. The TCF7L2 gene is located on chromosome 10q25.2–q25.3, con ...
, or NKD1 Naked cuticle 1 (NKD1) is a human gene that encodes the protein Nkd1, a member of the Naked cuticle (Nkd) family of proteins that regulate the Wnt signaling pathway. Insects typically have a single Nkd gene, whereas there are two Nkd genes, Nkd1 an ...
.
Beyond the defects in the Wnt signaling pathway
The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling p ...
, other mutations must occur for the cell to become cancerous. The p53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
protein, produced by the ''TP53'' gene, normally monitors cell division
Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
and induces their programmed death if they have Wnt pathway defects. Eventually, a cell line
An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cell ...
acquires a mutation in the ''TP53'' gene and transforms the tissue from a benign epithelial tumor into an invasive epithelial cell cancer. Sometimes the gene encoding p53 is not mutated, but another protective protein named BAX is mutated instead.
Other proteins responsible for programmed cell death that are commonly deactivated in colorectal cancers are TGF-β
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...
and DCC (Deleted in Colorectal Cancer
Netrin receptor DCC, also known as DCC, or colorectal cancer suppressor is a protein which in humans is encoded by the ''DCC'' gene. DCC has long been implicated in colorectal cancer and its previous name was ''Deleted in colorectal carcinoma''. ...
). 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 is deactivated. DCC commonly has a deleted segment of a chromosome in colorectal cancer.
Approximately 70% of all human gene
This article is an index of lists of human genes.
By chromosome
Below is a list of articles on human chromosomes, each of which contains an incomplete list of genes located on that chromosome.
* Chromosome 1 (human)
* Chromosome 2 (human)
* Chr ...
s are expressed in colorectal cancer, with just over 1% of having increased expression in colorectal cancer compared to other forms of cancer. Some genes are oncogenes
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels. : they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS
''KRAS'' (Kirsten rat sarcoma virus) is a gene that provides instructions for making a protein called K-Ras, a part of the RAS/MAPK pathway. The protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell ...
, RAF
The Royal Air Force (RAF) is the United Kingdom's air and space force. It was formed towards the end of the First World War on 1 April 1918, becoming the first independent air force in the world, by regrouping the Royal Flying Corps (RFC) and ...
, and PI3K
Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which i ...
, 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. If a previous APC mutation occurred, a primary KRAS mutation often progresses to cancer rather than a self-limiting hyperplastic
Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferatio ...
or borderline lesion. PTEN, a tumor suppressor, normally inhibits PI3K, but can sometimes become mutated and deactivated.
Comprehensive, genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
-scale analysis has revealed that colorectal carcinomas can be categorized into hypermutated and non-hypermutated tumor types. In addition to the oncogenic and inactivating mutations described for the genes above, non-hypermutated samples also contain mutated CTNNB1
Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcripti ...
, FAM123B, SOX9
Transcription factor SOX-9 is a protein that in humans is encoded by the ''SOX9'' gene.
Function
SOX-9 recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins. It is expressed by proliferating but no ...
, ATM, and ARID1A
AT-rich interactive domain-containing protein 1A is a protein that in humans is encoded by the ''ARID1A'' gene.
Function
ARID1A is a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate t ...
. Progressing through a distinct set of genetic events, hypermutated tumors display mutated forms of ACVR2A
Activin receptor type-2A is a protein that in humans is encoded by the ''ACVR2A'' gene.
ACVR2A is an activin type 2 receptor.
Function
This gene encodes activin A type II receptor. Activins are dimeric growth and differentiation factors which ...
, TGFBR2
Transforming growth factor, beta receptor II (70/80kDa) is a TGF beta receptor. ''TGFBR2'' is its human gene.
It is a tumor suppressor gene.
Function
This gene encodes a member of the serine/threonine protein kinase family and the TGFB recepto ...
, MSH3
DNA mismatch repair protein, MutS Homolog 3 (MSH3) is a human homologue of the bacterial mismatch repair protein MutS that participates in the mismatch repair (MMR) system. MSH3 typically forms the heterodimer MutSβ with MSH2 in order to correc ...
, MSH6
MSH6 or mutS homolog 6 is a gene that codes for DNA mismatch repair protein Msh6 in the budding yeast ''Saccharomyces cerevisiae''. It is the homologue of the human "G/T binding protein," (GTBP) also called p160 or hMSH6 (human MSH6). The MSH6 prot ...
, SLC9A9, TCF7L2
Transcription factor 7-like 2 (T-cell specific, HMG-box), also known as TCF7L2 or TCF4, is a protein acting as a transcription factor that, in humans, is encoded by the ''TCF7L2'' gene. The TCF7L2 gene is located on chromosome 10q25.2–q25.3, con ...
, and BRAF. The common theme among these genes, across both tumor types, is their involvement in Wnt and TGF-β signaling pathways, which results in increased activity of MYC
''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' (MYC), ''l-myc'' ( MYCL), and ''n-myc'' (MYCN). ''c-myc'' (also sometimes refe ...
, a central player in colorectal cancer.
Mismatch repair
DNA mismatch repair (MMR) is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of bases that can arise during DNA replication and recombination, as well as repairing some forms of DNA damage.
Mismatch ...
(MMR) deficient tumours are characterized by a relatively high amount of poly-nucleotide tandem repeat
Tandem repeats occur in DNA when a pattern of one or more nucleotides is repeated and the repetitions are directly adjacent to each other. Several protein domains also form tandem repeats within their amino acid primary structure, such as armadil ...
s. This is caused by a deficiency in MMR proteins – which are typically caused by epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
silencing and or inherited mutations (''e.g.'', Lynch syndrome
Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that is associated with a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ovary, ...
). 15 to 18 percent of colorectal cancer tumours have MMR deficiencies, with 3 percent developing due to Lynch syndrome. The role of the mismatch repair system is to protect the integrity of the genetic material within cells (''i.e.'', error detecting and correcting). Consequently, a deficiency in MMR proteins may lead to an inability to detect and repair genetic damage, allowing for further cancer-causing mutations to occur and colorectal cancer to progress.
The polyp to cancer progression sequence is the classical model of colorectal cancer pathogenesis
Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
. The polyp to cancer sequence describes the phases of transition from benign
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malign ...
tumours into colorectal cancer over many years. Central to the polyp to CRC sequence are gene mutations, epigenetic alterations, and local inflammatory changes. The polyp to CRC sequence can be used as an underlying framework to illustrate how specific molecular changes lead to various cancer subtypes.
Field defects
The term "field cancerization" was first used in 1953 to describe an area or "field" of epithelium that has been preconditioned (by what were largely unknown processes at the time) to predispose it towards development of cancer. Since then, the terms "field cancerization", "field carcinogenesis", "field defect", and " field effect" have been used to describe pre-malignant or pre-neoplastic tissue in which new cancers are likely to arise.
Field defects are important in progression to colon cancer.
However, as pointed out by Rubin, "The vast majority of studies in cancer research has been done on well-defined tumors ''in vivo'', or on discrete neoplastic foci ''in vitro''. Yet there is evidence that more than 80% of the somatic mutations found in mutator phenotype human colorectal tumors occur before the onset of terminal clonal expansion." Similarly, Vogelstein et al. pointed out that more than half of somatic mutations identified in tumors occurred in a pre-neoplastic phase (in a field defect), during growth of apparently normal cells. Likewise, epigenetic alterations present in tumors may have occurred in pre-neoplastic field defects.
An expanded view of field effect has been termed "etiologic field effect", which encompasses not only molecular and pathologic changes in pre-neoplastic cells but also influences of exogenous environmental factors and molecular changes in the local microenvironment on neoplastic evolution from tumor initiation to death.
Epigenetics
Epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
alterations are much more frequent in colon cancer than genetic (mutational) alterations. As described by Vogelstein et al., an average cancer of the colon has only 1 or 2 oncogene mutations and 1 to 5 tumor suppressor mutations (together designated "driver mutations"), with about 60 further "passenger" mutations. The oncogenes and tumor suppressor genes are well studied and are described above under Pathogenesis
Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
.
In addition to epigenetic alteration of expression of miRNAs, other common types of epigenetic alterations in cancers that change gene expression levels include direct hypermethylation or hypomethylation of CpG islands of protein-encoding genes and alterations in histones and chromosomal architecture that influence gene expression. As an example, 147 hypermethylations and 27 hypomethylations of protein coding genes were frequently associated with colorectal cancers. Of the hypermethylated genes, 10 were hypermethylated in 100% of colon cancers, and many others were hypermethylated in more than 50% of colon cancers. In addition, 11 hypermethylations and 96 hypomethylations of miRNAs were also associated with colorectal cancers. Abnormal (aberrant) methylation
In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...
occurs as a normal consequence of normal aging and the risk of colorectal cancer increases as a person gets older. The source and trigger of this age-related methylation is unknown. Approximately half of the genes that show age-related methylation changes are the same genes that have been identified to be involved in the development of colorectal cancer. These findings may suggest a reason for age being associated with the increased risk of developing colorectal cancer.
Epigenetic reductions of DNA repair enzyme expression may likely lead to the genomic and epigenomic instability characteristic of cancer. As summarized in the articles Carcinogenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...
and Neoplasm
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
, for sporadic cancers in general, a deficiency in DNA repair is occasionally due to a mutation in a DNA repair gene, but is much more frequently due to epigenetic alterations that reduce or silence expression of DNA repair genes.
Epigenetic alterations involved in the development of colorectal cancer may affect a person's response to chemotherapy.
Genomics , Epigenomics
Consensus molecular subtypes (CMS) classification of colorectal cancer was first introduced in 2015. CMS classification so far has been considered the most robust classification system available for CRC that has a clear biological interpretability and the basis for future clinical stratification and subtype-based targeted interventions.
A novel Epigenome-based Classification (EpiC) of colorectal cancer was proposed in 2021 introducing 4 enhancer subtypes in people with CRC. Chromatin states using 6 histone marks are characterized to identify EpiC subtypes. A combinatorial therapeutic approach based on the previously introduced consensus molecular subtypes (CMSs) and EpiCs could significantly enhance current treatment strategies.
Diagnosis
Colorectal cancer diagnosis is performed by sampling of areas of the colon suspicious for possible tumor development, typically during colonoscopy or sigmoidoscopy, depending on the location of the lesion.[ It is confirmed by microscopical examination of a tissue sample.
]
Medical imaging
A colorectal cancer is sometimes initially discovered on CT scan.
Presence of metastases
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
is determined by a CT scan of the chest, abdomen and pelvis. Other potential imaging tests such as PET
A pet, or companion animal, is an animal kept primarily for a person's company or entertainment rather than as a working animal, livestock, or a laboratory animal. Popular pets are often considered to have attractive appearances, intelligence, ...
and MRI
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
may be used in certain cases. The latter is often used for rectal lesions to determine its local stage and to facilitate preoperative planning.
Histopathology
The histopathologic
Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία ''-logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spec ...
characteristics of the tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
are reported from the analysis of tissue taken from a biopsy or surgery. A pathology report contains a description of the microscopical characteristics of the tumor tissue, including both tumor cells and how the tumor invades into healthy tissues and finally if the tumor appears to be completely removed. The most common form of colon cancer is adenocarcinoma
Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ) (AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or ...
, constituting between 95% to 98% of all cases of colorectal cancer. Other, rarer types include lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...
, adenosquamous and squamous cell carcinoma
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
. Some subtypes are more aggressive. Immunohistochemistry
Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to an ...
may be used in uncertain cases.
Staging
Staging
Staging may refer to:
Computing
* Staging (cloud computing), a process used to assemble, test, and review a new solution before it is moved into production and the existing solution is decommissioned
* Staging (data), intermediately storing data ...
of the cancer is based on both radiological and pathological findings. As with most other forms of cancer, tumor staging is based on the TNM system which considers how much the initial tumor has spread and the presence of metastases in lymph nodes and more distant organs. The AJCC 8th edition was published in 2018.
Prevention
It has been estimated that about half of colorectal cancer cases are due to lifestyle factors, and about a quarter of all cases are preventable. Increasing surveillance, engaging in physical activity, consuming a diet high in fiber, and reducing smoking and alcohol consumption decrease the risk.
Lifestyle
Lifestyle risk factors with strong evidence include lack of exercise, cigarette smoking, alcohol, and obesity. The risk of colon cancer can be reduced by maintaining a normal body weight through a combination of sufficient exercise and eating a healthy diet
A healthy diet is a diet that maintains or improves overall health. A healthy diet provides the body with essential nutrition: fluid, macronutrients such as protein, micronutrients such as vitamins, and adequate fibre and food energy.
A healthy ...
.
Current research consistently links eating more red meat and processed meat to a higher risk of the disease. Starting in the 1970s, dietary recommendations to prevent colorectal cancer often included increasing the consumption of whole grains
A whole grain is a grain of any cereal and pseudocereal that contains the endosperm, germ, and bran, in contrast to refined grains, which retain only the endosperm.
As part of a general healthy diet, consumption of whole grains is associated wi ...
, fruits and vegetables, and reducing the intake of red meat
In gastronomy, red meat is commonly red when raw and a dark color after it is cooked, in contrast to white meat, which is pale in color before and after cooking. In culinary terms, only flesh from mammals or fowl (not fish) is classified as ...
and processed meat
Processed meat is considered to be any meat which has been modified in order to either improve its taste or to extend its shelf life. Methods of meat processing include salting, curing, fermentation, smoking, and/or the addition of chemical pre ...
s. This was based on animal studies and retrospective observational studies. However, large scale prospective studies have failed to demonstrate a significant protective effect, and due to the multiple causes of cancer and the complexity of studying correlations between diet and health, it is uncertain whether any specific dietary interventions will have significant protective effects.[ In 2018 the ]National Cancer Institute
The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
stated that "There is no reliable evidence that a diet started in adulthood that is low in fat and meat and high in fiber, fruits, and vegetables reduces the risk of CRC by a clinically important degree."
According to the World Cancer Research Fund
World Cancer Research Fund International is a not-for-profit association related to cancer prevention research related to diet
Diet may refer to:
Food
* Diet (nutrition), the sum of the food consumed by an organism or group
* Dieting, the del ...
, consuming alcohol drinks and consuming processed meat both increase the risk of colorectal cancer.
The 2014 World Health Organization cancer report noted that it has been hypothesized that dietary fiber might help prevent colorectal cancer, but most studies have not borne this out, and status of the science remained unclear as of 2014. A 2019 review, however, found evidence of benefit from dietary fiber and whole grains. The World Cancer Research Fund
World Cancer Research Fund International is a not-for-profit association related to cancer prevention research related to diet
Diet may refer to:
Food
* Diet (nutrition), the sum of the food consumed by an organism or group
* Dieting, the del ...
listed the benefit of fiber for prevention of colorectal cancer as "probable" as of 2017. A 2022 umbrella review In medical research, an umbrella review is a review of systematic reviews or meta-analyses. They may also be called overviews of reviews, reviews of reviews, summaries of systematic reviews, or syntheses of reviews. Umbrella reviews are among the hi ...
says there is "convincing evidence" for that association.
Higher physical activity is recommended.[ ]Physical exercise
Exercise is a body activity that enhances or maintains physical fitness and overall health and wellness.
It is performed for various reasons, to aid growth and improve strength, develop muscles and the cardiovascular system, hone athletic ...
is associated with a modest reduction in colon but not rectal cancer risk. High levels of physical activity reduce the risk of colon cancer by about 21%. Sitting
Sitting is a basic action and resting position in which the body weight is supported primarily by the bony ischial tuberosities with the buttocks in contact with the ground or a horizontal surface such as a chair seat, instead of by the lower l ...
regularly for prolonged periods is associated with higher mortality from colon cancer. Regular exercise does not negate the risk but does lower it.
Medication and supplements
Aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
and celecoxib
Celecoxib, sold under the brand name Celebrex among others, is a COX-2 inhibitor and nonsteroidal anti-inflammatory drug (NSAID). It is used to treat the pain and inflammation in osteoarthritis, acute pain in adults, rheumatoid arthritis, ankyl ...
appear to decrease the risk of colorectal cancer in those at high risk. Aspirin is recommended in those who are 50 to 60 years old, do not have an increased risk of bleeding, and are at risk for cardiovascular disease to prevent colorectal cancer. It is not recommended in those at average risk.
There is tentative evidence for calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
supplementation, but it is not sufficient to make a recommendation. Vitamin D
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
intake and blood levels are associated with a lower risk of colon cancer.
Screening
As more than 80% of colorectal cancers arise from adenomatous polyps, screening for this cancer is effective for both early detection and for prevention. Diagnosis of cases of colorectal cancer through screening tends to occur 2–3 years before diagnosis of cases with symptoms.[ Any polyps that are detected can be removed, usually by ]colonoscopy
Colonoscopy () or coloscopy () 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 can provide a visual diagnosis (''e. ...
or sigmoidoscopy
Sigmoidoscopy (from the Greek term for letter " s/ς" + "eidos" + "scopy": namely, to look inside an "s"/"ς"-like object) is the minimally invasive medical examination of the large intestine from the rectum through to the nearest part of the co ...
, and thus prevent them from turning into cancer. Screening has the potential to reduce colorectal cancer deaths by 60%.[
The three main screening tests are colonoscopy, ]fecal occult blood
Fecal occult blood (FOB) refers to blood in the feces that is not visibly apparent (unlike other types of blood in stool such as melena or hematochezia). A fecal occult blood test (FOBT) checks for hidden (occult) blood in the stool (feces).
The ...
testing, and flexible sigmoidoscopy
Sigmoidoscopy (from the Greek term for letter " s/ς" + "eidos" + "scopy": namely, to look inside an "s"/"ς"-like object) is the minimally invasive medical examination of the large intestine from the rectum through to the nearest part of the co ...
. Of the three, only sigmoidoscopy cannot screen the right side of the colon where 42% of cancers are found. Flexible sigmoidoscopy, however, has the best evidence for decreasing the risk of death from any cause.
Fecal occult blood testing (FOBT) of the stool is typically recommended every two years and can be either guaiac-based or immunochemical.[ If abnormal FOBT results are found, participants are typically referred for a follow-up colonoscopy examination. When done once every 1–2 years, FOBT screening reduces colorectal cancer deaths by 16% and among those participating in screening, colorectal cancer deaths can be reduced up to 23%, although it has not been proven to reduce all-cause mortality. Immunochemical tests are accurate and do not require dietary or medication changes before testing. However, research in the UK has found that for these immunochemical tests, the threshold for further investigation is set at a point that may miss more than half of bowel cancer cases. The research suggests that the NHS England’s Bowel Cancer Screening Programme could make better use of the test's ability to provide the exact concentration of blood in faeces (rather than only whether it is above or below a cutoff level).]
Other options include virtual colonoscopy
Virtual colonoscopy (VC, also called CT colonography or CT pneumocolon) is the use of CT scanning or magnetic resonance imaging (MRI) to produce two- and three-dimensional images of the colon (large intestine), from the lowest part, the rectum, ...
and stool DNA screening testing (FIT-DNA). Virtual colonoscopy via a CT scan appears as good as standard colonoscopy for detecting cancers and large adenomas but is expensive, associated with radiation exposure, and cannot remove any detected abnormal growths as standard colonoscopy can.[ Stool DNA screening test looks for ]biomarker
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...
s associated with colorectal cancer and precancerous lesions, including altered DNA and blood hemoglobin. A positive result should be followed by colonoscopy
Colonoscopy () or coloscopy () 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 can provide a visual diagnosis (''e. ...
. FIT-DNA has more false positives than FIT and thus results in more adverse effects.[ Further study is required as of 2016 to determine whether a three-year screening interval is correct.]
Recommendations
In the United States, screening is typically recommended between ages 50 to 75 years. The American Cancer Society
The American Cancer Society (ACS) is a nationwide voluntary health organization dedicated to eliminating cancer. Established in 1913, the society is organized into six geographical regions of both medical and lay volunteers operating in more than ...
recommends starting at the age of 45. For those between 76 and 85 years old, the decision to screen should be individualized.[ For those at high risk, screenings usually begin at around 40.]
Several screening methods are recommended including stool-based tests every 2 years, sigmoidoscopy
Sigmoidoscopy (from the Greek term for letter " s/ς" + "eidos" + "scopy": namely, to look inside an "s"/"ς"-like object) is the minimally invasive medical examination of the large intestine from the rectum through to the nearest part of the co ...
every 10 years with fecal immunochemical testing every two years, and colonoscopy
Colonoscopy () or coloscopy () 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 can provide a visual diagnosis (''e. ...
every 10 years.[ It is unclear which of these two methods is better.][ Colonoscopy may find more cancers in the first part of the colon, but is associated with greater cost and more complications.] For people with average risk who have had a high-quality colonoscopy with normal results, the American Gastroenterological Association
The American Gastroenterological Association (AGA) is a medical association of gastroenterologists. Approximately 16,000 scientists and physicians are members of the organization.
Overview
The American Gastroenterological Association is a prof ...
does not recommend any type of screening in the 10 years following the colonoscopy. For people over 75 or those with a life expectancy of less than 10 years, screening is not recommended. It takes about 10 years after screening for one out of a 1000 people to benefit. The USPSTF list seven potential strategies for screening, with the most important thing being that at least one of these strategies is appropriately used.[
In Canada, among those 50 to 75 years old at normal risk, fecal immunochemical testing or FOBT is recommended every two years or sigmoidoscopy every 10 years.][ Colonoscopy is less preferred.]
Some countries have national colorectal screening programs which offer FOBT screening for all adults within a certain age group, typically starting between ages 50 to 60. Examples of countries with organised screening include the United Kingdom, Australia, the Netherlands, Hong Kong, and Taiwan.
The UK Bowel Cancer Screening Programme aims to find warning signs in people aged 60 to 74, by recommending a faecal immunochemical test (FIT) every two years. FIT measures blood in faeces, and people with levels above a certain threshold may have bowel tissue examined for signs of cancer. Growths having cancerous potential are removed.
Treatment
The treatment of colorectal cancer can be aimed at cure or palliation. The decision on which aim to adopt depends on various factors, including the person's health and preferences, as well as the stage of the tumor. Assessment in multidisciplinary teams is a critical part of determining whether the patient is suitable for surgery or not. When colorectal cancer is caught early, surgery can be curative. However, when it is detected at later stages (for which metastases
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
are present), this is less likely and treatment is often directed at palliation, to relieve symptoms caused by the tumour and keep the person as comfortable as possible.
Surgery
At an early stage, colorectal cancer may be removed during a colonoscopy using one of several techniques, including endoscopic mucosal resection
Endoscopic mucosal resection is a technique used to remove cancerous or other abnormal lesions found in the digestive tract. It is one method of performing a mucosectomy.
For the esophagous
Endoscopic mucosal resection has been advocated for ...
or endoscopic submucosal dissection
Endoscopic submucosal dissection (ESD) is an advanced surgery, surgical procedure using endoscopy to remove gastrointestinal cancer, gastrointestinal tumors that have not entered the muscle layer. ESD may be done in the esophagus, stomach or colon ...
.[ For people with localized cancer, the preferred treatment is complete surgical removal with adequate margins, with the attempt of achieving a cure. The procedure of choice is a partial ]colectomy
Colectomy ('' col-'' + '' -ectomy'') is bowel resection of the large bowel ( colon). It consists of the surgical removal of any extent of the colon, usually segmental resection (partial colectomy). In extreme cases where the entire large intestin ...
(or proctocolectomy for rectal lesions) where the affected part of the colon or rectum is removed along with parts of its mesocolon
The mesentery is an organ that attaches the intestines to the posterior abdominal wall in humans and is formed by the double fold of peritoneum. It helps in storing fat and allowing blood vessels, lymphatics, and nerves to supply the intestine ...
and blood supply
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
to facilitate removal of draining lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s. This can be done either by an open laparotomy
A laparotomy is a surgical procedure involving a surgical incision through the abdominal wall to gain access into the abdominal cavity. It is also known as a celiotomy.
Origins and history
The first successful laparotomy was performed without ane ...
or laparoscopic
Laparoscopy () is an operation performed in the abdomen or pelvis using small incisions (usually 0.5–1.5 cm) with the aid of a camera. The laparoscope aids diagnosis or therapeutic interventions with a few small cuts in the abdomen.Medli ...
ally, depending on factors related to the individual person and lesion factors. The colon may then be reconnected or a person may have a colostomy
A colostomy is an opening ( stoma) in the large intestine (colon), or the surgical procedure that creates one. The opening is formed by drawing the healthy end of the colon through an incision in the anterior abdominal wall and suturing it int ...
.[
If there are only a few metastases in the liver or lungs, these may also be removed. ]Chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
may be used before surgery to shrink the cancer before attempting to remove it. The two most common sites of recurrence of colorectal cancer are the liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
and lungs
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of th ...
.[ For peritoneal carcinomatosis cytoreductive surgery, sometimes in combination with HIPEC can be used in an attempt to remove the cancer.]
Chemotherapy
In both cancer of the colon and rectum
The rectum is the final straight portion of the large intestine in humans and some other mammals, and the Gastrointestinal tract, gut in others. The adult human rectum is about long, and begins at the rectosigmoid junction (the end of the s ...
, chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
may be used in addition to surgery in certain cases. The decision to add chemotherapy in management of colon and rectal cancer depends on the stage of the disease.
In Stage I colon cancer, no chemotherapy is offered, and surgery is the definitive treatment. The role of chemotherapy in Stage II colon cancer is debatable, and is usually not offered unless risk factors such as T4 tumor, undifferentiated tumor, vascular and perineural invasion or inadequate lymph node sampling is identified. It is also known that the people who carry abnormalities of the mismatch repair genes do not benefit from chemotherapy. For stage III and Stage IV colon cancer, chemotherapy is an integral part of treatment.[
If cancer has spread to the ]lymph nodes
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
or distant organs, which is the case with stage III and stage IV colon cancer respectively, adding chemotherapy agents fluorouracil
Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancreat ...
, capecitabine
Capecitabine, sold under the brand name Xeloda among others, is a chemotherapy medication used to treat breast cancer, gastric cancer and colorectal cancer. For breast cancer it is often used together with docetaxel. It is taken by mouth.
Comm ...
or oxaliplatin
Oxaliplatin, sold under the brand name Eloxatin among others, is a cancer medication (platinum-based antineoplastic class) used to treat colorectal cancer. It is given by injection into a vein.
Common side effects include numbness, feeling ti ...
increases life expectancy. If the lymph nodes do not contain cancer, the benefits of chemotherapy are controversial. If the cancer is widely metastatic or unresectable, treatment is then palliative
Palliative care (derived from the Latin root , or 'to cloak') is an interdisciplinary medical caregiving approach aimed at optimizing quality of life and mitigating suffering among people with serious, complex, and often terminal illnesses. Wit ...
. Typically in this setting, a number of different chemotherapy medications may be used. Chemotherapy drugs for this condition may include capecitabine
Capecitabine, sold under the brand name Xeloda among others, is a chemotherapy medication used to treat breast cancer, gastric cancer and colorectal cancer. For breast cancer it is often used together with docetaxel. It is taken by mouth.
Comm ...
, fluorouracil
Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancreat ...
, irinotecan
Irinotecan, sold under the brand name Camptosar among others, is a medication used to treat colon cancer, and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is used with cispl ...
, oxaliplatin
Oxaliplatin, sold under the brand name Eloxatin among others, is a cancer medication (platinum-based antineoplastic class) used to treat colorectal cancer. It is given by injection into a vein.
Common side effects include numbness, feeling ti ...
and UFT. The drugs capecitabine and fluorouracil are interchangeable, with capecitabine being an oral medication and fluorouracil being an intravenous medicine. Some specific regimen
A regimen is a plan, or course of action such as a diet, exercise or medical treatment. A low-salt diet is a regimen. A course of penicillin is a regimen, and there are many chemotherapy regimens in the treatment of cancer.
History
The work, ' ...
s used for CRC are CAPOX
CAPOX (also called XELOX) is a chemotherapy regimen consisting of capecitabine ( trade name Xeloda) combined with oxaliplatin.
Xelox regime operates in 3-week cycles, usually with 8 cycles in total; Xeloda is orally taken for twice daily for two w ...
, FOLFOX, FOLFOXIRI FOLFOXIRI is a chemotherapy regimen for The treatment of advanced colorectal cancer. The role of FOLFOXIRI in colorectal cancer has been reviewed.
The chemotherapy regimen is made up of the following four drugs:
* FOL – folinic acid (leucovorin) ...
, and FOLFIRI FOLFIRI is a chemotherapy regimen for treatment of colorectal cancer. It is made up of the following drugs:
* FOL – folinic acid (leucovorin), a vitamin B derivative used as a "rescue" drug for high doses of the drug methotrexate, but increases ...
. Antiangiogenic drugs such as bevacizumab
Bevacizumab, sold under the brand name Avastin among others, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, l ...
are often added in first line therapy. Another class of drugs used in the second line setting are epidermal growth factor receptor
The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands.
The epidermal growth factor recept ...
inhibitors, of which the three FDA approved ones are aflibercept
Aflibercept, sold under the brand names Eylea and Zaltrap, is a medication used to treat wet macular degeneration and metastatic colorectal cancer. It was developed by Regeneron Pharmaceuticals and is approved in the United States and the Europ ...
, cetuximab
Cetuximab, sold under the brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor medication used for the treatment of metastatic colorectal cancer and head and neck cancer. Cetuximab is a chimeric (mouse/human) monoclonal an ...
and panitumumab
Panitumumab, sold under the brand name Vectibix, is a fully human monoclonal antibody specific to the epidermal growth factor receptor (also known as ''EGF receptor'', ''EGFR'', ''ErbB-1'' and ''HER1'' in humans).
Panitumumab is manufactured by ...
.
The primary difference in the approach to low stage rectal cancer is the incorporation of radiation therapy. Often, it is used in conjunction with chemotherapy in a neoadjuvant
Neoadjuvant therapy is the administration of therapeutic agents before a main treatment. One example is neoadjuvant hormone therapy prior to radical radiotherapy for adenocarcinoma of the prostate. Neoadjuvant therapy aims to reduce the size o ...
fashion to enable surgical resection, so that ultimately a colostomy
A colostomy is an opening ( stoma) in the large intestine (colon), or the surgical procedure that creates one. The opening is formed by drawing the healthy end of the colon through an incision in the anterior abdominal wall and suturing it int ...
is not required. However, it may not be possible in low lying tumors, in which case, a permanent colostomy may be required. Stage IV rectal cancer is treated similar to stage IV colon cancer.
Stage IV colorectal cancer due to peritoneal carcinomatosis
Peritoneal carcinomatosis (PC) is intraperitoneal dissemination ( carcinosis) of any form of cancer that does not originate from the peritoneum itself. PC is most commonly seen in abdominopelvic malignancies. Computed tomography (CT) is particu ...
can be treated using HIPEC combined with cytoreductive surgery, in some people.
Radiation therapy
While a combination of radiation
In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or through a material medium. This includes:
* ''electromagnetic radiation'', such as radio waves, microwaves, infrared, visi ...
and chemotherapy may be useful for rectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of th ...
,[ for some people requiring treatment, chemoradiotherapy can increase acute treatment-related toxicity, and has not been shown to improve survival rates compared to radiotherapy alone, although it is associated with less local recurrence.] The use of radiotherapy in colon cancer is not routine due to the sensitivity of the bowels to radiation. As with chemotherapy, radiotherapy can be used as a neoadjuvant for clinical stages T3 and T4 for rectal cancer. This results in downsizing or downstaging of the tumour, preparing it for surgical resection, and also decreases local recurrence rates. For locally advanced rectal cancer, neoadjuvant chemoradiotherapy has become the standard treatment. Additionally, when surgery is not possible radiation therapy has been suggested to be an effective treatment against CRC pulmonary metastases, which are developed by 10-15% of people with CRC.
Immunotherapy
Immunotherapy
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
with immune checkpoint inhibitors has been found to be useful for a type of colorectal cancer with mismatch repair deficiency
DNA mismatch repair (MMR) is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of bases that can arise during DNA replication and recombination, as well as repairing some forms of DNA damage.
Mismatch ...
and microsatellite instability. Pembrolizumab
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast canc ...
is approved for advanced CRC tumours that are MMR deficient and have failed usual treatments. Most people who do improve, however, still worsen after months or years.[
On the other hand, in a prospective phase 2 study published in June 2022 in The New England Journal of Medicine, 12 patients with Deficient Mismatch Repair (dMMR) stage II or III rectal adenocarcinoma were administered single-agent ]dostarlimab
Dostarlimab, sold under the brand name Jemperli, is a monoclonal antibody used as an anti-cancer medication for the treatment of endometrial cancer. Dostarlimab is a Programmed cell death protein 1, programmed death receptor-1 (PD-1)–blocking ...
, an anti–PD-1 monoclonal antibody, every three weeks for six months. After a median follow-up of 12 months (range, 6 to 25 months), all 12 patients had a complete clinical response with no evidence of tumor on MRI, 18F-fluorodeoxyglucose–positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy. Moreover, no patient in the trial needed chemoradiotherapy or surgery, and no patient reported adverse events of grade 3 or higher. However, although the results of this study are promising, the study is small and has uncertainties about long-term outcomes.
Palliative care
Palliative care
Palliative care (derived from the Latin root , or 'to cloak') is an interdisciplinary medical caregiving approach aimed at optimizing quality of life and mitigating suffering among people with serious, complex, and often terminal illnesses. Wit ...
is recommended for any person who has advanced colon cancer or who has significant symptoms.
Involvement of palliative care may be beneficial to improve the quality of life for both the person and his or her family, by improving symptoms, anxiety and preventing admissions to the hospital.
In people with incurable colorectal cancer, palliative care can consist of procedures that relieve symptoms or complications from the cancer but do not attempt to cure the underlying cancer, thereby improving quality of life
Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...
. Surgical options may include non-curative surgical removal of some of the cancer tissue, bypassing part of the intestines, or stent placement. These procedures can be considered to improve symptoms and reduce complications such as bleeding from the tumor, abdominal pain and intestinal obstruction. Non-operative methods of symptomatic treatment include radiation therapy to decrease tumor size as well as pain medications.
Follow-up
The U.S. National Comprehensive Cancer Network
National Comprehensive Cancer Network (NCCN) is an alliance of 32 cancer centers in the United States, most of which are designated by the National Cancer Institute (one of the U.S. National Institutes of Health) as comprehensive cancer centers. It ...
and American Society of Clinical Oncology
The American Society of Clinical Oncology (ASCO) is a professional organization representing physicians of all oncology sub-specialties who care for people with cancer. Founded in 1964 by Fred Ansfield, Harry Bisel, Herman Freckman, Arnoldus G ...
provide guidelines for the follow-up of colon cancer. A medical history
The medical history, case history, or anamnesis (from Greek: ἀνά, ''aná'', "open", and μνήσις, ''mnesis'', "memory") of a patient is information gained by a physician by asking specific questions, either to the patient or to other peo ...
and physical examination
In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally consists of a series of questions about the patien ...
are recommended every 3 to 6 months for 2 years, then every 6 months for 5 years. Carcinoembryonic antigen
Carcinoembryonic antigen (CEA) describes a set of highly related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth. Consequently, CEA is ...
blood level measurements follow the same timing, but are only advised for people with T2 or greater lesions who are candidates for intervention. A CT-scan of the chest, abdomen and pelvis can be considered annually for the first 3 years for people who are at high risk of recurrence (for example, those who had poorly differentiated tumors or venous or lymphatic invasion) and are candidates for curative surgery (with the aim to cure). A colonoscopy
Colonoscopy () or coloscopy () 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 can provide a visual diagnosis (''e. ...
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
A pet, or companion animal, is an animal kept primarily for a person's company or entertainment rather than as a working animal, livestock, or a laboratory animal. Popular pets are often considered to have attractive appearances, intelligence, ...
or ultrasound scanning, chest X-ray
A chest radiograph, called a chest X-ray (CXR), or chest film, is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common film taken in med ...
s, complete blood count
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cell ...
or liver function tests
Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...
are not recommended.
For people who have undergone curative surgery or adjuvant therapy (or both) to treat non-metastatic colorectal cancer, intense surveillance and close follow-up have not been shown to provide additional survival benefits.
Exercise
Exercise may be recommended in the future as secondary therapy to cancer survivors. In epidemiological studies, exercise may decrease colorectal cancer-specific mortality and all-cause mortality. Results for the specific amounts of exercise needed to observe a benefit were conflicting. These differences may reflect differences in tumour biology and the expression of biomarkers. People with tumors that lacked CTNNB1
Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcripti ...
expression (β-catenin), involved in Wnt signalling pathway
The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling p ...
, required more than 18 Metabolic equivalent
The metabolic equivalent of task (MET) is the objective measure of the ratio of the rate at which a person expends energy, relative to the mass of that person, while performing some specific physical activity compared to a reference, set by convent ...
(MET) hours per week, a measure of exercise, to observe a reduction in colorectal cancer mortality. The mechanism of how exercise benefits survival may be involved in immune surveillance and inflammation pathways. In clinical studies, a pro-inflammatory response was found in people with stage II-III colorectal cancer who underwent 2 weeks of moderate exercise after completing their primary therapy. Oxidative balance may be another possible mechanism for benefits observed. A significant decrease in 8-oxo-dG was found in the urine of people who underwent 2 weeks of moderate exercise after primary therapy. Other possible mechanisms may involve metabolic hormone and sex-steroid hormones, although these pathways may be involved in other types of cancers.
Another potential biomarker may be p27. Survivors with tumors that expressed p27 and performed greater and equal to 18 MET hours per week were found to have reduced colorectal cancer mortality survival compared to those with less than 18 MET hours per week. Survivors without p27 expression who exercised were shown to have worse outcomes. The constitutive activation of PI3K/AKT/mTOR pathway
The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates A ...
may explain the loss of p27 and excess energy balance may up-regulate p27 to stop cancer cells from dividing.
Physical activity provides benefits to people with non-advanced colorectal cancer. Improvements in aerobic fitness, cancer-related fatigue and health-related quality of life have been reported in the short term. However, these improvements were not observed at the level of disease-related mental health, such as anxiety and depression.
Prognosis
Fewer than 600 genes are linked to outcomes in colorectal cancer. These include both unfavorable genes, where high expression is related to poor outcome, for example the heat shock 70 kDa protein 1 (HSPA1A), and favorable genes where high expression is associated with better survival, for example the putative RNA-binding protein 3 (RBM3).[
]
Recurrence rates
The average five-year recurrence rate in people where surgery is successful is 5% for stage I cancers, 12% in stage II and 33% in stage III. However, depending on the number of risk factors it ranges from 9–22% in stage II and 17–44% in stage III.
Survival rates
In Europe the five-year survival rate
The five-year survival rate is a type of survival rate for estimating the prognosis of a particular disease, normally calculated from the point of diagnosis. Lead time bias from earlier diagnosis can affect interpretation of the five-year surviva ...
for colorectal cancer is less than 60%. In the developed world
A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state that has a high quality of life, developed economy and advanced technological infrastruct ...
about a third of people who get the disease die from it.
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 are about five times that of late stage cancers. People with a tumor that has not breached the muscularis mucosa
The lamina muscularis mucosae (or muscularis mucosae) is a thin layer (lamina) of muscle of the gastrointestinal tract, located outside the lamina propria, and separating it from the submucosa. It is present in a continuous fashion from the es ...
(TNM stage Tis, N0, M0) have a five-year survival rate of 100%, while those with invasive cancer of T1 (within the submucosal layer) or T2 (within the muscular layer) have an average five-year survival rate of approximately 90%. Those with a more invasive tumor yet without node involvement (T3-4, N0, M0) have an average five-year survival rate of approximately 70%. People with positive regional lymph nodes (any T, N1-3, M0) have an average five-year survival rate of approximately 40%, while those with distant metastases (any T, any N, M1) have a poor prognosis and the five year survival ranges from <5 percent to 31 percent.[ ] The prognosis depends on a multitude of factors which include the physical fitness level of the person, extent of metastases, and tumor grade.
Whilst the impact of colorectal cancer on those who survive varies greatly there will often be a need to adapt to both physical and psychological outcomes of the illness and its treatment. For example, it is common for people to experience incontinence, sexual dysfunction, problems with stoma care and fear of cancer recurrence after primary treatment has concluded.
A qualitative systematic review published in 2021 highlighted that there are three main factors influencing adaptation to living with and beyond colorectal cancer: support mechanisms, severity of late effects of treatment and psychosocial adjustment. Therefore, it is essential that people are offered appropriate support to help them better adapt to life following treatment.
Epidemiology
Globally more than 1 million people get colorectal cancer every year resulting in about 715,000 deaths as of 2010 up from 490,000 in 1990.
, it is the second most common cause of cancer in women (9.2% of diagnoses) and the third most common in men (10.0%)[ with it being the fourth most common cause of cancer death after ]lung
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
, stomach
The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...
, and liver cancer
Liver cancer (also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy) is cancer that starts in the liver. Liver cancer can be primary (starts in liver) or secondary (meaning cancer which has spread from elsewhere to th ...
. It is more common in developed than developing countries. Global incidence varies 10-fold, with highest rates in Australia, New Zealand, Europe and the US and lowest rates in Africa and South-Central Asia.[; ]
United States
In 2022, the incidence of colorectal cancer in the United States was anticipated to be about 151,000 adults, including over 106,000 new cases of colon cancer (some 54,000 men and 52,000 women) and about 45,000 new cases of rectal cancer. Since the 1980s, the incidence of colorectal cancer decreased, dropping by about 2% annually from 2014 to 2018 in adults aged 50 and older, due mainly to improved screening.[
]
United Kingdom
In the UK about 41,000 people a year get colon cancer making it the fourth most common type.
Australia
One in 19 men and one in 28 women in Australia will develop colorectal cancer before the age of 75; one in 10 men and one in 15 women will develop it by 85 years of age.
Papua New Guinea
In the developing countries like Papua New Guinea and other Pacific Island States including the Solomon Islands, colorectal cancer is a very rare cancer amongst the people, which is least common compared to lung, stomach, liver or breast cancer. It is estimated that at least 8 in 100,000 of the people are most likely to developed colorectal cancer every year, which is unlike lung or breast cancer, where for the latter alone is 24 in 100,000 of the women folks alone.
History
Rectal cancer has been diagnosed in an Ancient Egyptian mummy
A mummy is a dead human or an animal whose soft tissues and organs have been preserved by either intentional or accidental exposure to chemicals, extreme cold, very low humidity, or lack of air, so that the recovered body does not decay fu ...
who had lived in the Dakhleh Oasis
Dakhla Oasis (Egyptian Arabic: , , "''the inner oasis"''), is one of the seven oases of Egypt's Western Desert. Dakhla Oasis lies in the New Valley Governorate, 350 km (220 mi.) from the Nile and between the oases of Farafra and Khar ...
during the Ptolemaic period.
Society and culture
In the United States, March is colorectal cancer awareness month.
Research
Preliminary in-vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology and ...
evidence suggests lactic acid bacteria
Lactobacillales are an order of gram-positive, low-GC, acid-tolerant, generally nonsporulating, nonrespiring, either rod-shaped (bacilli) or spherical (cocci) bacteria that share common metabolic and physiological characteristics. These bacte ...
(e.g., lactobacilli
The ''Lactobacillaceae'' are a family of lactic acid bacteria. It is the only family in the lactic acid bacteria which includes homofermentative and heterofermentative organisms; in the ''Lactobacillaceae,'' the pathway used for hexose fermentati ...
, streptococci
''Streptococcus'' is a genus of gram-positive ' (plural ) or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell division in streptococci occurs ...
or lactococci
''Lactococcus'' is a genus of lactic acid bacteria that were formerly included in the genus ''Streptococcus'' Group N1. They are known as homofermenters meaning that they produce a single product, lactic acid in this case, as the major or only pr ...
) may be protective against the development and progression of colorectal cancer through several mechanisms such as antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
activity, immunomodulation, promoting programmed cell death
Programmed cell death (PCD; sometimes referred to as cellular suicide) is the death of a cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usually confers advantage durin ...
, antiproliferative effects, and epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
modification of cancer cells.
Mouse models of colorectal and intestinal cancer Mouse models of colorectal cancer and intestinal cancer are experimental systems in which mice are genetically manipulated, fed a modified diet, or challenged with chemicals to develop malignancies in the gastrointestinal tract. These models enab ...
have been developed and are used in research.
* The Cancer Genome Atlas
''The'' () is a grammatical article in English, denoting persons or things already mentioned, under discussion, implied or otherwise presumed familiar to listeners, readers, or speakers. It is the definite article in English. ''The'' is the m ...
* The Colorectal Cancer Atlas integrating genomic and proteomic data pertaining to colorectal cancer tissues and cell lines have been developed.
References
External links
*
{{DEFAULTSORT:Colorectal Cancer
Conditions diagnosed by stool test
Infectious causes of cancer
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