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.
Types of Tumours Associated with Lynch Syndrome
Lynch syndrome is most commonly associated with the development of colorectal cancers and uterine cancers, however it has also been linked to other types of tumours.
Some examples include:
Treatment
When cancers are detected, they are staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) 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 cancer 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 cancer present.
- Cancer location.
- Whether or not the cancer has metastasised.
- Your age.
- General health.
- Your treatment preferences.
Your doctor may also recommend genetic testing, 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.
- Chemotherapy.
- Radiation therapy.
- Cryotherapy.
- Targeted therapy.
- Immunotherapy.
- Watch and wait.
- Hormone therapy.
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia treatment options page.
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.
Early symptoms
The symptoms of Lynch syndrome often vary by the type(s) of tumours present.
Symptoms of Colorectal Cancer
In the early stages of colorectal cancer, the disease may be asymptomatic. As the cancer progresses, some of the following symptoms may appear:
- 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.
- Anal and/or rectal pain.
- A lump in the anus or rectum.
- Unexplained weight loss.
- Unexplained fatigue.
- Anaemia – potentially causing fatigue, weakness and/or weight loss.
- Changes in urinary habits, such as:
- Blood in urine.
- Frequent urination, especially at night.
- Changes in urine colour – becoming dark, rusty or brown colour.
Symptoms of Uterine Cancer
The symptoms of uterine cancers often vary by subtype:
Symptoms of Ovarian Cancer
The symptoms of ovarian cancer often vary by subtype:
Symptoms of Bladder Cancer
The symptoms of a bladder cancer may include:
- Blood in your urine (haematuria).
- Burning feeling when you urinate.
- Increased frequency of urination.
- Increased urgency of urination.
- Constipation.
- Pain when urinating (dysuria).
- Persistent urinary tract infections (UTIs).
- Unexplainable weight loss.
- Fatigue.
- Incontinence (involuntary loss of urine).
- Abdominal pain (rare).
Symptoms of Stomach (Gastric) Cancer
The symptoms of a stomach cancer may include:
- Unexplained weight loss and/or loss of appetite.
- Difficulties swallowing.
- Indigestion, which may carry its own set of symptoms:
- Abdominal pain/burning.
- Heartburn.
- Frequent burping.
- Reflux.
- Nausea and/or vomiting.
- Abdominal pain.
- Feeling full after eating small quantities of food.
- Abdominal swelling and/or bloating.
- Fatigue.
- Anaemia.
- Vomit with blood in it.
- Discoloured stools.
Symptoms of Small Bowel Cancer
The symptoms of small bowel cancers may include:
- Abdominal pain.
- Unexplained weight loss.
- A lump in the abdomen.
- Blood in stools.
- Changes in bowel habits, such as:
- Nausea and/or vomiting.
- Fatigue.
- Anaemia.
- Jaundice (yellowing of the eyes and/or skin).
Symptoms of Hepatobiliary Cancers
The symptoms of hepatobiliary cancers often vary by subtype:
Symptoms of Kidney Cancer
The symptoms of kidney cancer often vary by subtype:
Symptoms of Brain Cancer
The symptoms of brain cancer will often vary by subtype:
Symptoms of Pancreatic Cancer
The symptoms of pancreatic cancer vary based on whether the cancer is classified as endocrine (hormone-producing) or exocrine (not hormone-producing).
Exocrine Pancreatic Cancer
The symptoms of exocrine pancreatic cancers may include:
- Jaundice (yellowing of the eyes and the skin).
- Changes in bathroom habits, such as dark urine and pale-coloured and greasy stools.
- Itchy skin.
- Abdominal and/or back pain.
- Unexplained weight loss/loss of appetite.
- Nausea and vomiting.
- Fatigue.
- Enlargement of the gallbladder.
- Blood clots in the leg.
- New, onset diabetes/changes in blood sugar levels.
- Indigestion.
Endocrine Pancreatic Cancer
The symptoms of endocrine pancreatic cancer often vary based on subtype:
Symptoms of Prostate Cancer
The symptoms of prostate cancer may include:
- Changes in urination, such as:
- Frequent need to urinate.
- Feeling like your bladder isn’t empty after urination.
- Slow urine flow.
- Weaker bladder.
- Loss of bladder control.
- Loss of bowel control.
- Blood in urine and/or semen.
- Erectile dysfunction.
- Pain when ejaculating.
- Unexplained weight loss.
- Bone pain.
Symptoms of Skin Cancer
Symptoms of skin cancers often vary by subtype.
Symptoms of Basal Cell Carcinomas
Symptoms of BCCs may include:
- Lumps on areas exposed to skin, including the head, face, neck, shoulders, lower arms and legs.
- Pearl-coloured lump.
- A pale or bright pink scaly area around the lump.
- Skin ulceration.
- Bleeding.
- Inflammation.
Symptoms of Squamous Cell Carcinomas
Symptoms of SCCs may include:
- Lumps on areas exposed to skin, including the head, face, neck, shoulders, lower arms and legs.
- Rapidly growing lump.
- Thickened, red, scaly or crusted spot.
- Bleeding.
- Inflammation.
- Tender to touch.
Symptoms of Melanoma
For the symptoms of melanoma of the skin, please refer to the Rare Cancers Australia Melanoma (Cutaneous) page.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis/diagnosing
If your doctor suspects you have 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 examination
Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.
Genetic testing
In addition to guiding treatment, genetic testing can be used to help diagnose certain conditions. Lynch syndrome has been linked to various genetic mutations, which changes specific protein functions. These changes can lead to cell abnormalities and, in extreme cases, cancer. Your doctor may perform genetic testing to better understand your condition.
Pelvic examination
The doctor will inspect the abdomen for any swelling or masses, followed by your genitalia. The doctor will then insert two fingers into your vagina while simultaneously pressing on your abdomen with their other hand to feel your uterus and ovaries. Following this, the doctor may use a device called a speculum into your vagina, which will separate the vaginal walls and allow viewing of your vaginal canal and cervix for any visible abnormalities. You many request a family member, friend or nurse to be present during this exam.
Imaging & Blood tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), x-ray and/or ultrasound, depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and looks for signs of metastasis. Additionally, a blood test may be taken to assess your overall health and help guide treatment decisions.
Neurological examination
A neurological examination assesses sensory and motor functions, and can generally be done in your GPs office. The doctor may check your vision, hearing, balance, coordination, strength, and reflexes, depending on the signs and symptoms you have described. Any problem that is detected in this exam can help determine which portion of the CNS needs further investigation.
Colonoscopy
A colonoscopy is the main diagnostic test used for colorectal cancers. This procedure examines the lining of the entire large bowel, and can detect if any polyps or abnormal tissue are present. Your doctor will insert a long, flexible tube with a light attached (colonoscope) through your anus, rectum and colon while you are under an anaesthetic. Carbon dioxide or air may be pumped through the colonoscope for better visualisation of the bowel.
Flexible Sigmoidoscopy
A flexible sigmoidoscopy is similar to a colonoscopy; however, this procedure only examines the rectum and lower portion of the colon. The instrument passed through the anus is shorter, and called a sigmoidoscope.
Biopsy
Once the location of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. This tissue will then be sent to the lab and analysed for cancer cells.
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the extent of the disease, susceptibility to treatment, age, overall fitness, and medical history. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.