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Lynch syndrome is an adult-onset hereditary condition that runs in families. It is associated with an increased risk of developing colorectal cancer as well as other cancers.
Approximately 2-5% of all colorectal cancer cases is associated with a hereditary cancer syndrome.
Estimates suggest that
one in 300 people may carry a faulty copy of a DNA mismatch repair (MMR) gene associated with Lynch syndrome.
Approximately, up to 5% of colorectal cancer and 3% of endometrial (uterine) cancer cases are caused by Lynch syndrome.
Largely caused by chance events, driven by age and environmental factors
A combination of genes and environmental factors resulting in an elevated cancer risk
There are different hereditary cancer syndromes associated with an increased risk of colorectal cancer, of which Lynch syndrome is the most common
Hereditary cancer makes up about 5-10% of all cases of cancer. Some genes function to protect us from cancer. When they are not working well, it causes hereditary cancer. We refer to genes that are not working well as faulty genes.
Individuals who carry a faulty cancer gene(s) have a higher chance of developing certain cancers over their lifetime compared to the general population. The types of cancers that they may be at increased risk of will depend on the gene(s) involved.
If you have a faulty cancer gene, you may be at increased risk of developing certain cancers. As genes are shared among family, other family members may have inherited the faulty gene and may be at increased risk of cancer too.
Hereditary cancer accounts for up to 10% of all cases of cancer.
Genetic testing is offered to individuals where a hereditary cause of their personal and/or family history of cancer is suspected.
Genes contain the instructions that our body reads to carry out different functions. Genetic testing involves analysing your genes to understand if there are faults (i.e., mutations) that may increase the risk of diseases like cancer.
There are 3 types of results you may receive:
Lynch syndrome is associated with a faulty (disease-causing) copy of MMR genes, namely
MLH1, MSH2, MSH6, PMS2, and EPCAM.
Individuals who have Lynch syndrome (carriers) face an increased risk of cancers, but it does not mean that they will definitely develop cancer. Carriers face different cancer risks depending on which faulty gene they have.
*inadequate dataNote: The conditions associated with Lynch syndrome and their risk estimates may change as more information is available.
References1. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Genetic/Familial High-Risk Assessment: Colorectal. Version 1.2020. 2020 July 21; National Comprehensive Cancer Network. 2. Dominguez-Valentin, M. et al (2020). Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genetics in Medicine, 22(1), 15–25. https://doi.org/10.1038/s41436-019-0596-9
Lynch syndrome increases the risk of cancer in both males and females.
Other less common cancers associated with Lynch syndrome are hepatobiliary tract cancer, small bowel cancer, brain cancer, and sebaceous neoplasms (skin cancer).
There are other genes aside from MMR genes that increase the risk of colorectal cancer (e.g., APC, POLE, POLD1, PTEN, CHEK2, MUTYH, NTHL1, MSH3) as part of other genetic conditions. Genetic testing for colorectal cancer will usually include testing of such genes as well.
Lynch syndrome follows a
dominant inheritance pattern. This means that having one faulty copy of any MMR gene (i.e., MLH1, MSH2, MSH6, PMS2 and EPCAM) can result in an increased risk of cancer.
Everyone has 2 copies of each gene in their body’s cells:
Occasionally, tumour or cancer testing may reveal results that can help guide if Lynch syndrome testing is needed for you. These tumour tests include:
You may be recommended to undergo additional tests to determine if genetic testing is needed for you.
Your personal and/or family history of cancer can also help guide if genetic testing for Lynch syndrome is needed. If you or your family members meet one or more of the following criteria, you can consider genetic testing:
*Lynch syndrome-related cancers:
Note: This list may change as more information is available
Personalised managementYour genetic test result may help to personalise your management options based on your cancer risk.
If you have a cancer diagnosis
If you are currently cancer-free
Familial implicationsYour genetic test result can also help you understand if other family members are at risk of Lynch syndrome. They can subsequently consider their own testing (predictive testing) to clarify their carrier status to determine tumour and cancer risks.Family members who have inherited the same faulty MMR gene may be at increased risk of tumours and cancer and can benefit from management options such as screening (to detect tumours and cancer at an early and manageable stage) or surgery (to reduce their risk of cancer).Family members who did not inherit the faulty MMR gene can avoid unnecessary screening and worry. Their children will also not be at risk.
Your managing doctor(s) will discuss screening recommendations with you in greater detail. The age and onset of screening may depend on your personal and/or family history of cancer. Screening guidelines may change as more information is known.
These options are not standard management practices but may be offered on a case-by-case basis. Surgery is generally offered to patients who have been diagnosed with cancer and require surgery as part of their treatment plan.
Individuals can consider removing both the uterus and ovaries at the same time to reduce the risk of cancer.
These options will be discussed in detail with you by your managing doctor(s). These surgeries reduce the risk of cancer significantly but do not remove the risk completely.
Couples who are both carriers of the same faulty MMR gene can consider assisted reproductive options when planning a pregnancy. Their children have a 1 in 4 chance (25%) of inheriting two faulty copies of the same MMR gene – one from each parent – resulting in a condition known as
constitutional mismatch repair deficiency (CMMRD) syndrome as shown below. Those who inherit two faulty copies of the same MMR gene have CMMRD.
Individuals with CMMRD are at risk of developing blood malignancies, brain tumours, and colon, small bowel, uterine, gastric, urologic and other types of cancer. They may develop multiple cancers throughout their lifetime and may present early in childhood.
We recommend people with Lynch syndrome to speak to a genetic counsellor prior to family planning and pregnancy to find out how their partners can undergo genetic testing to understand their carrier status, and to understand their options for assisted reproductive techniques.