Most colorectal cancers occur randomly or by chance (sporadically). Although about 20%–30% of people with colorectal cancer have a family history of this cancer, less than 10% of all colorectal cancers are due to a hereditary or inherited gene mutation. Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), is the most common type of hereditary colorectal cancer. About 2%–5% of all colorectal cancers are due to Lynch syndrome. People with Lynch syndrome have a greatly increased chance of developing colorectal cancer, especially at a young age (usually under 50).
Unlike familial adenomatous polyposis (FAP), most people with Lynch syndrome do not have an unusual number of colon polypspolypsA small cauliflower-like growth on a mucous membrane, such as the lining of the colon, bladder, uterus (womb), vocal cords or nasal passage.. If they do have colon polyps, they occur at an earlier age than in the general population. Although people with Lynch syndrome don’t have more polyps than people in the general population, the polyps that do develop are more likely to become cancerous.
Women with Lynch syndrome also have an increased risk of uterine (endometrial) cancer.
Other, rarer hereditary gene mutations are associated with an increased risk of colorectal cancer, but these are not discussed here.
People with Lynch syndrome have a mutation in one of 4 genes that normally correct mistakes when deoxyribonucleic acid (DNA)deoxyribonucleic acid (DNA)The molecules inside the cell that program genetic information. DNA determines the structure, function and behaviour of a cell. is copied during cell division. These genes are called DNA mismatch repair genes (MMR).
The 4 main MMR genes associated with Lynch syndrome are MLH1, MSH2, MSH6 and PMS2. Most mutations (90%) that cause Lynch syndrome are found in the MLH1 or MSH2 genes. The other 2 genes, MSH6 and PMS2, and possibly others, account for the other 10% of mutations.
Researchers have also identified different gene mutations associated with Lynch syndrome, but these are rare. Other mutations may be discovered in the future.
Men and women can inherit a gene mutation associated with Lynch syndrome from either their mother or father. People with one of these mutations can also pass it on to their children. If one parent has the mutation in 1 of the 2 copies of a Lynch syndrome gene, a child has a 50% chance of inheriting the gene mutation. This also means there is a 50% chance that a child will not inherit the gene mutation.
Healthcare professionals use certain criteria to determine if a Lynch syndrome gene mutation may be present in a family. These are referred to as the Amsterdam criteria.
People with Lynch syndrome often have several family members with colorectal cancer and other cancers related to Lynch syndrome. These cancers are often diagnosed at younger ages than usually expected and often occur in several generations.
People with Lynch syndrome have a 70%–80% chance of developing colorectal cancer in their lifetime (lifetime risklifetime riskThe chance or probability that a person will develop a particular disease over his or her entire life.). Their level of risk depends on which gene mutation they have. Cancerous tumours usually develop in the part of the colon closest to the small intestine (the ascending or right side of the colon). Women with Lynch syndrome have a 40%–60% lifetime risk of developing uterine cancer.
People with Lynch syndrome are also at risk for other cancers, including ovarian, small intestine, stomach, pancreatic, urinary tract, liver, biliary tract, skin and brain cancer. These cancers occur less commonly in people with Lynch syndrome than colorectal or uterine cancer.
There are 2 variants of Lynch syndrome:
Genetic testing is available for specific types of hereditary colorectal cancer syndromes. It can be used to confirm a suspected diagnosis, clarify the risk of cancer in affected people and identify relatives who are also at risk.
It may be possible to diagnose Lynch syndrome when several family members on the same side of the family have colorectal cancer or a person develops multiple cancers during their lifetime. A diagnosis of Lynch syndrome or a family history of Lynch syndrome is the main risk factor that suggests genetic testing for a gene mutation related to Lynch syndrome.
In most cases, genetic testing for Lynch syndrome begins on a sample from a colorectal or uterine tumour. Special tests, called microsatellite instability (MSI) assay and immunohistochemical (IHC) analysis, are done to see if the tumour has a Lynch syndrome gene mutation. If the tumour tests positive for Lynch syndrome, a blood sample is taken and genetic testing is done to look for Lynch syndrome gene mutations. The person will also receive genetic counselling.
A healthcare professional will determine if people are eligible for genetic screening. If they qualify for testing, they will likely be referred to a genetic program where geneticists or genetic counsellors do more detailed assessments. In Canada, genetic testing to see if a family member carries a gene mutation related to Lynch syndrome is done through hereditary (familial) cancer programs. People have to meet certain criteria before they have genetic testing for hereditary colorectal cancer.
People who know they have a Lynch syndrome gene mutation (they tested positive for one of the Lynch syndrome-related genes) should talk to their doctor about taking steps to help reduce their risk of cancer and to find it early.
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