Introduction to Colorectal Cancer
The Gastrointestinal System
The term colorectal refers to both the colon and the rectum. The colon and the rectum form part of the digestive tract, also called the gastrointestinal or GI tract.
The gastrointestinal tract is a long tube that runs through the body, starting at the mouth and ending at the anus. After food is swallowed, it moves along the tube where it gets broken down, nutrients are absorbed into the blood, and any unusable portion is removed as waste.
Digestion begins in the mouth with the chewing of food (mechanical digestion) as well as the initial breakdown of starches by enzymes in the saliva (chemical digestion). The stomach continues the digestive process by secreting gastric juices and mixing them with food to break it down.
The mixture of food and gastric juices empties into the small intestine, a long, coiled, hose-like organ. Here the food continues to be churned and digested. The majority of nutrients from food are absorbed into the bloodstream along the length of the small intestine.
Undigested food substances that cannot be absorbed, such as vegetable fibre, move from the small intestine into the large intestine. The large intestine, also called the bowel, is divided into seven areas: the cecum, the ascending, transverse, descending and sigmoid colon; the rectum and the anus (see illustration). The large intestine is about 1.5 metres long, with the rectum making up the last 13cm.
The colon removes water as well as some nutrients and minerals from the remainder of the food contents. Any remaining food matter that has passed through the colon is solid waste, called feces. The feces eventually move through to the end of the colon and reach the rectum, leaving the body through the anus.
The colon’s main functions are to:
Re-absorb water and some nutrients such as the salts sodium, potassium and chloride from what we eat
Formation and compaction of waste
Fermentation of some indigestible food matter by beneficial bacteria
What is cancer?
Normal cells in the body grow and multiply in an orderly and controlled way.
Sometimes, mistakes occur in the DNA or genetic information of the cell. These mistakes are known as mutations. If a cell accumulates certain mutations, they may cause it to behave abnormally. Certain mutations may cause a cell to continue to multiply uncontrollably, or to ignore its instructions to die. Eventually, enough of these abnormal cells may multiply to form a solid mass called a tumour.
How colorectal cancer develops
Colorectal cancer includes two types of cancers: cancer of the colon (large intestine or bowel) referred to as colon cancer, and cancer of the rectum (the end portion of the large intestine) or rectal cancer. Both types of cancer have many features in common, so they are collectively called colorectal cancer.
Generally, colorectal cancer spreads fairly slowly, more slowly than some other cancers. It can stay in the colon or rectum for months or years, and, if it is not treated, can spread beyond the large intestine or rectum, first to the lymph nodes and then to other distant organs. If caught in the early stages, colorectal cancer is often curable.
Most colorectal cancers evolve from small mushroom-like growths known as polyps. Sometimes the polyps can be flat, making them harder to detect. While most polyps are benign, as they evolve they may become cancerous.
Over time, the benign polyp may grow through some or all of the tissue layers that make up the colon and rectum and become malignant, invading nearby tissues and structures. Eventually, malignant tumour cells can reach the blood and lymphatic system and travel to other parts of the body such as the liver, lung, abdomen or brain, causing cancer to develop in these organs. When the cancer spreads to a distant organ it has metastasized. The spread of the cancer to another organ is called metastasis.
Colorectal cancer can spread through:
tissue. Cancer invades the surrounding normal tissue.
the lymphatic system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.
Signs and symptoms of colorectal cancer
Being aware of the common signs and symptoms of colorectal cancer is important. If you notice any of the following symptoms, be sure to let your doctor know as soon as possible:
Unexplained changes in bowel habits, such as constipation or diarrhea
Change in size/shape of stools, such as being narrower than usual
Blood in or on the stool, ranging from bright red to dark black
Persistent abdominal pain/discomfort including bloating, fullness, cramps, gas pain
Unexplained weight loss
For more information on early age onset colorectal cancer, see our Never Too Young (N2Y) for Colorectal Cancer Program:
Colorectal cancer risk factors
Risk factors that increase the chance of developing colorectal cancer include:
a family history of colorectal cancer
a personal history of colorectal cancer
inflammatory bowel disease, such as ulcerative colitis
You are more likely to develop colorectal cancer if someone in your immediate family (parent, sibling or child) has been diagnosed with it. The risk of colorectal cancer increases if you have two or more close relatives who have been diagnosed with colorectal cancer or if a relative is diagnosed with it before the age of 50.
Inflammatory Bowel Disease
If you have had inflammatory bowel disease (not including irritable bowel syndrome) for a long period of time, you may be at a higher risk of developing colorectal cancer.
Certain individuals may have an inherited predisposition to developing colorectal cancer or polyps. Five to ten percent of patients with colorectal cancer have an inherited genetic mutation that puts them at a greater risk of colorectal cancer.
Hereditary nonpolyposis colorectal cancer (HNPCC), which is also known as Lynch syndrome, is responsible for a small percentage of colorectal cancers (2% to 5% of patients). Though people affected by HNPCC have few polyps, the polyps are more likely to become cancerous and at a faster rate.
Familial adenomatous polyposis (FAP), also accounts for only a small number of colorectal cancers (1% of patients). People affected by FAP can develop thousands of polyps (also called adenomas) along the inside wall of the colon. These polyps are likely to turn cancerous by the time a person reaches their early 40s, so FAP is best treated by preventative surgery to remove the colon.
Another condition called Peutz-Jeghers Syndrome is characterized by the development of benign polyps in the gastrointestinal tract. These can lead to a greater risk in the development of cancerous polyps over time.
If you have already had colorectal cancer or polyps in the past, you are more likely to develop new cancers in others parts of the colon or rectum.
The older you are, the more likely you are to develop colorectal cancer. Most people who are diagnosed with colorectal cancer are 50 years or older; however, it is becoming more common in people under the age of 50 when screening is less common and symptoms often go unnoticed. For more resources on early-onset colorectal cancer, please see our Never too Young program.
Cancer and genetics
All cancer begins with genetic changes or mutations. Our genes are distinct sequences of DNA that contain the blueprint of all the unique functions of our body. Some genes control cell division and cell growth. When mutations occur in these genes, a cell may begin to grow and divide abnormally, eventually becoming cancer.
Mutations may be caused by aging, or exposure to certain environmental factors such as chemicals or radiation. Over time, the genes contained within a cell may accumulate various mutations, which cause it to divide and grow in a way that becomes cancerous. Since it usually takes years to acquire the genetic mutations that lead to cancer, it explains why the majority of cancers such as colorectal occur at a later age.
About 5-10% of colorectal cancer, however, can be attributed to hereditary or inherited factors passed down from parent to child. This means that a small percentage of people are born with certain genetic mutations that make it more likely for them to develop cancer. Inherited gene mutations help to explain why some families have more people with certain kinds of cancers.
Important terms to know:
Genetics: the study of heredity
Genomics: the branch of molecular biology concerned with the structure, function, evolution, and mapping of all the genetic material present in a cell or organism (the genome).
The main difference between genomics and genetics is that genetics examines the functioning and composition of a single gene whereas genomics addresses all genes and their inter-relationships in order to identify their combined influence on the growth and development of the organism (World Health Organization).
What is genetic testing?
Genetic testing is a type of medical test that closely examines a person’s DNA or genetic code to look for any changes or mutations that are linked to known diseases. If any known mutations are found, the results can confirm or rule out a particular genetic condition or help to determine a person’s chance of developing or passing on a genetic disorder.
How is genetic testing done?
Genetic testing is done by analyzing the DNA present in a blood sample. There are three main methods used for genetic testing:
Molecular genetic tests examine single genes or short lengths of DNA to identify variations or mutations that can cause a genetic disorder
Chromosomal genetic tests analyze whole chromosomes or complex structures of DNA to look for any large genetic changes, such as an extra copy of a whole chromosome, that can cause a genetic condition
Biochemical genetic tests study the amount of activity level of proteins, which are coded for by the genes in our DNA. Abnormalities in the amount of level of proteins can indicate changes to the DNA that result in a genetic disorder.
Remember that genetic testing is voluntary. A geneticist or genetic counselor can help you by providing information about the pros and cons of the test and discuss any social and emotional aspects of testing.
Lynch Syndrome and Colorectal Cancer
Lynch Syndrome or hereditary non-polyposis colorectal cancer (HNPCC) is a type of inherited or genetic disorder passed from parent to child that increases the risk of developing several types of cancer, especially colorectal cancer, at a younger age (before 50 years old). It is the most common inherited cause of colorectal cancer – up to 5% of all colorectal cancers are thought to be related to Lynch syndrome.
Other cancer risks of Lynch syndrome
People with Lynch syndrome also have an increased risk of developing cancers of the:
skin compared to the general population.
Genetics and Lynch Syndrome
Lynch syndrome occurs when inherited changes or mutations occur in genes that regulate DNA mismatch repair, a process that corrects mistakes that are made when DNA is copied. The genes that are affected (MLHL, KSH2, MSH6, PMS2, EPCAM) are known as mismatch repair genes and are important in the prevention of cancer; when they are mutated, it becomes easier for cancer to develop.
Lynch syndrome & Microsatellite instability (MSI)
Tumours that develop when someone has Lynch syndrome typically show microsatellite instability (MSI). A microsatellite is a stretch of DNA that contains a repetitive sequence.
When a mutation in a mismatch repair gene is present, these microsatellites will show abnormalities in their sequences compared to normal tissue, resulting in microsatellite instability.
About 90% of colorectal cancer that occurs in people with Lynch syndrome shows MSI while about 15% of sporadic colorectal cancers (those that do not arise due to an inherited gene mutation) show MSI.
Everyone has two copies of each gene involved in Lynch syndrome – one from their mother and one from their father. Even when a person inherits a mutation in a gene involved in Lynch syndrome, they still have one normal copy of the gene from the other parent. Cancer only occurs once a second acquired mutation affects the other normal gene so that both genes are mutated. As a result, people who carry a mutation do carry an increased risk of cancer but not all people who have mutations will necessarily develop cancer.
Lynch syndrome is inherited in an autosomal dominant pattern, which means that if a parent is a carrier of the mutation, they have a 50% chance of passing it on to their children.
Family Health History & Colorectal Cancer
Knowing your family health history is important. If there is a strong history of colorectal cancer or if one of your family members has a known Lynch syndrome gene mutation, be sure to talk to your doctor about genetic testing. Studies show that conversations between patients and their healthcare provider is the strong driver of screening participation.
Risks of developing Lynch syndrome
A person is considered high risk for Lynch syndrome if one or more of the following characteristics can be confirmed in your family:
A person with colorectal cancer at age 40 or younger;
A person with colorectal cancer and another Lynch syndrome cancer, with one diagnosed at age 50 or younger;
Two close family members with a Lynch syndrome cancer at age 50 or younger;
Three close family members (over more than one generation) with a Lynch syndrome cancer, including at least once case of colorectal cancer and at least one cancer diagnosed at age 50 or younger.
(BC Cancer Agency)
It is recommended that tumours always be verified by biopsy and other colorectal cancer-related syndromes such as familial adenoma polyposis (FAP) should be ruled out.
Fill out our colorectal cancer Family History Chart to better understand your family history of the disease.
Benefits of genetic testing for colorectal cancer
While no one wants to find out that they have an inherited genetic mutation that could lead to cancer, knowing can help to control your risk.
Early colorectal cancer surveillance and risk reduction: A positive test result that indicates the presence of Lynch syndrome mutations can lead to appropriate disease surveillance and risk reduction for affected individuals and their family members.
Early colorectal cancer detection: Genetic testing can also help to better explain the history of cancer in a family. When detected early, colorectal cancer has a 90% cure rate. By participating in genetic testing, positive health behaviours can be reinforced and cancer can be caught early when it is more treatable.
What should I do if I’m worried Lynch syndrome runs in my family?
If you suspect that Lynch syndrome may be in your family, talk to your doctor for details on how to get tested. Remember that in Canada, if you test positive for Lynch syndrome, it will not affect your public health insurance coverage. On July 10, 2020, the Supreme Court of Canada upheld the Genetic Non Discrimination Act (S.C 2017, c. 3), which prohibits any person from requiring an individual to undergo a genetic test or to disclose the existing results of their genetic tests. In Canada, it is prohibited for any person to collect, use or disclose your genetic test results without your written consent (Office of the Privacy Commissioner of Canada).
Limitations of genetic testing
Although genetic testing can provide important information about your health, there are several limitations to how useful this information can be. Consider the following before getting tested:
If you test positive for a mutation that is linked to cancer, it does not necessarily mean that you will develop cancer
If you test negative for a mutation that is linked to cancer, it doesn’t mean that you will not develop cancer
The current genetic tests that are available only look for certain mutations, meaning that some mutations that can cause cancer may not be detected
Not all family members want to know their risk of disease
Results may increase anxiety in some people
Genetic test results can lead to more medical appointments, tests and procedures if you do test positive for a gene mutation
Who can have genetic testing?
Not everyone qualifies for genetic testing. By examining your personal and family history, your doctor will see if genetic testing is right for you. Remember that genetic testing does not happen without genetic counseling and informed consent of each individual getting tested.
Index test for colorectal cancer
The first test (index test) in a family is usually done on the person with the highest chance of having a mutation, such as a person who has had colon cancer. Results can take many months.
Carrier test for colorectal cancer
If the index test does find a mutation, other family members may choose to do a carrier test. A carrier test is only offered once a genetic mutation has already been found in the family. This genetic test will only look for that specific mutation using a blood sample. Results usually take weeks.
How is genetic testing for Lynch syndrome done?
Genetic testing for Lynch syndrome usually begins with immunohistochemical (IHC) testing that looks at the proteins found in the colon tumour. If the IHC test finds that the proteins associated with the mismatch repair genes (MLHL, KSH2, MSH6, PMS2, EPCAM) are absent in the tumour sample, further testing can be performed on a blood sample.
This test will try to find a specific mutation in one of the Lynch syndrome genes. Possible results include:
The index test may not identify a specific mutation. This means that even if there is a mutation that is being passed down in the family, it cannot currently be detected. Carrier tests are not offered to other family members.
The index test identifies a genetic change known as a variant of uncertain significance. This means that while there is a change observed in a gene, it is unknown whether this change causes cancer. Carrier tests are not offered to other family members.
Index testing finds a mutation. Carrier tests are available to blood relatives who want to learn about their genetic status.
Managing your colorectal cancer risk
If you discover that you have Lynch syndrome, you are at a higher risk for cancer than the general population. This means that it is important to get screened more often for cancer compared to the average person. Early surveillance and screening can help to detect cancer at earlier stages when it is easier to treat.
The following cancer screening guidelines are recommended for people with Lynch syndrome:
Colonoscopy beginning at 20-25 years old or 10 years younger than the first colorectal cancer diagnosis in the family, whichever comes first.
Colonoscopy screening should happen every 1-2 years until age 40.
After age 40, colonoscopy should be done every year.
a research program that studies families with inherited colorectal cancer syndromes
Familial adenomatous polyposis (FAP) and Colorectal Cancer
What is Familial adenomatous polyposis (FAP)?
FAP is an inherited disorder that causes people to develop many noncancerous (benign) growths (polyps) in the colon as early as their teenage years. It is diagnosed when a person develops more than 100 benign colon polyps.
Over time, if the polyps are not recognized and removed, there is a very high chance that they will develop into colorectal cancer.
Less than 1% of all colorectal cancer is believed to be caused by FAP.
Other risks of FAP
People who have this condition also have an increased chance of developing cancer in other organs, such as the stomach, small intestine, and pancreas.
Genetics and FAP
Mutations in the APC gene are linked to the development of the condition, and are passed from parent to child. The mutation in the APC gene follows an autosomal dominant inheritance pattern, meaning that a parent who carries the mutation has a 50% of passing on the mutation to their child.
FAP may also be caused by mutations in the MUTYH gene, which is inherited in an autosomal recessive inheritance pattern. This means that while parents may not show any signs and symptoms of the condition, there is a 25% chance that one of their children will have this type of FAP.
What should I do if I’m worried FAP runs in my family?
If you are concerned that FAP may run in your family, talk to your healthcare team about your risk and screening options. You may decide to have genetic testing to confirm or rule out the condition.
What should I do if I’m diagnosed with FAP?
If you are diagnosed with FAP, screening for colorectal cancer will be different than the average person. Be sure to discuss screening with your health care team since each person’s condition is unique.
Colorectal cancer screening
Colorectal cancer screening for individuals with FAP may include:
sigmoidoscopy or colonoscopy every 1-2 years, starting at age 10 to 11.
Yearly colonoscopy once polyps are found until a colectomy (surgical removal of the entire colon) is planned.
After colon surgery, doctors will monitor the patient’s lower tract with sigmoidoscopy, every 6-12 months if some rectal tissue remains, or every 1-4 years if all rectal tissue has been removed.
Upper endoscopy at age 25-30, or once colorectal polyps are found, whichever happens first. This screening test helps to watch for polyps in the small intestine.
Yearly ultrasound of the thyroid gland may be considered starting at age 25 to 30.
Computed tomography (CT) scan or magnetic resonance imaging (MRI) may be recommended