Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC) syndrome, is a rare genetic condition that increases the risk of developing certain types of cancer. It is caused by an alteration in one of five genes in our DNA: MLH1, MSH2, MSH6, PMS2 and EpCAM.
Familial cancer syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased risk of cancer as the result of inherited genetic mutations in certain cancer-related genes. They can affect both adults and children, however they generally develop in people at a younger age than normal. While familial cancer syndromes are not classified as cancer, they are equally as severe and can be life-threatening as they are associated with the development of various tumours throughout the body. Having a familial cancer syndrome does not guarantee the development of cancer, however the risk of developing cancer is higher than those who do not have a familial cancer syndrome.
Lynch syndrome is generally diagnosed equally among the sexes, and is often diagnosed before the age of 50. However, anyone can develop the disease.
Lynch Syndrome Related Tumours
Lynch syndrome is most commonly associated with the development of colorectal and uterine tumours, however it has also been linked to other types of tumours. Some examples include:
- Colorectal (bowel) cancer.
- Endometrial cancer.
- Ovarian cancer, most commonly epithelial ovarian cancer.
- Stomach cancer.
- Small intestine cancer.
- Cholangiocarcinoma.
- Gallbladder cancer.
- Ampullary cancer.
- Pancreatic cancer.
- Bladder cancer.
- Upper tract urothelial cancer (UTUC).
- Prostate cancer.
- Brain cancers, most commonly gliomas.
- Skin cancer.
Treatment
When cancers are detected, they are staged and graded based on size, metastasis, and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you. However, each patient with Lynch syndrome will present with a unique disease behaviour, with varying tumour locations and symptoms. As such, there is no one treatment method that will work for everyone, and there is no standard staging system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- Type of tumours present.
- Whether the tumours are malignant (cancerous) or benignnot cancerous, can grow but will not spread to other body parts (non-cancerous).
- Tumour location.
- Whether or not malignant tumours have metastasised.
- Your age.
- General health.
- Your treatment preferences.
Your doctor may also recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment options for tumours associated with Lynch syndrome may include:
- Surgery to remove as much of the tumour(s) as possible – these will vary based on tumour type and location.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells.
- Hormone therapymedication that alters the levels of certain hormones in the body, such as oestrogen and progesterone.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Cancer Screening
Once a diagnosis of Lynch syndrome has been confirmed, implementing a targeted screening plan becomes essential due to the increased risk of developing certain cancers. The content of this plan will vary from person to person based on the genetic mutation involved, your family’s history of cancer and the types of cancers that may be present. It will also outline the routine tests you should have and how regularly you should have them. Some recommendations for Lynch syndrome may include:
- Annual physical examinations with family education surrounding signs and symptoms of related tumours.
- Colonoscopyan examination of the large intestine/bowel with a small, flexible instrument known as a colonoscope every 1-2 years starting at age 25 (for MLH1 and MSH2 mutations) or 30-35 (for MSH6 or PMS2 mutations), or five years before the earliest known cancer in the family was diagnosed (whichever comes first).
Screening options for Lynch syndrome may evolve as new technologies are developed and our understanding of the condition grows. It is essential to discuss your individual circumstances with your healthcare team to determine the most appropriate screening plan for you.
Risk factors
Lynch syndrome is caused by a genetic mutation in one of the following genes:
- MLH1.
- MSH2.
- MSH6.
- PMS2.
- EpCAM.
The first four genes are known as mismatch repair (MMR) genes. MMR genes are responsible for recognising and repairing errors in our DNA sequence that may occur during DNA replication. A mutation in any one of the MMR genes means that an error in the DNA sequence cannot be repaired, and may cause an accumulation of genetic mutations. This can predispose a person to cancer.
EpCAM (epithelial cell adhesion molecule) gene is responsible for producing the EpCAM protein, which helps epithelial cells stick together. While this gene is not an MMR gene, it is also a cause of Lynch syndrome because of its closeness to the MSH2 gene. Certain genetic mutations in the EpCAM gene can cause the MSH2 gene to shut off, resulting in the same accumulation of genetic mutations as above.
Symptoms
The symptoms of Lynch syndrome often vary by the type(s) of tumours present. General symptoms of Lynch syndrome may include:
- Changes in bowel movements, potentially including:
- Diarrhoea.
- Constipation.
- Feeling of incomplete bowel movement.
- Thin bowel stools.
- Blood in stools.
- Rectal bleeding.
- Abdominal pain, bloating and/or cramping.
- A lump in the anus or rectum.
- Unexplained weight loss and/or loss of appetite.
- Unexplained fatigue.
- Anaemiaa condition where there aren't enough red blood cells in the blood, causing fatigue, weakness and pale skin and affecting how the body responds to infection – potentially causing fatigue, weakness and/or weight loss.
Symptoms related to specific tumours can be found on our knowledgebase.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis
If your doctor suspects you have tumours associated with Lynch syndrome, they may order some of the following tests to confirm the diagnosis and refer you to a specialist for treatment. The tests required for diagnosis will often vary based on the symptoms present, and where the tumour(s) are suspected to be located.
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Genetic testing.
- Pelvic examination.
- Neurological examinationan assessment of sensory and motor functions, such as vision, balance and coordination.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Imaging tests, potentially including:
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.
- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
- Exploratory procedures, potentially including:
- Flexible sigmoidoscopyexamination of the lower portion of the large intestine and rectum with small, flexible instrument known as a sigmoidoscope .
- Colonoscopy.
- Gastroscopyexamination of the stomach and part of the small bowel with a small, flexible instrument known as a gastroscope
- Biopsyremoval of a section of tissue to analyse for cancer cells.