Lynch Syndrome: Causes, Symptoms, Treatment, Diagnosis, Epidemioogy, Pathophsiology

Amongst the many types of cancers, some are acquired while some others are hereditary or occur due to an inherited gene mutation. Colorectal cancer is one such type of cancer which indicates a high risk of the presence of a syndrome known as Lynch Syndrome as the cause of the cancer development. Not just colorectal cancer but this disorder or syndrome also indicates a high risk of developing stomach cancer, urinary tract cancer, tumour in central nervous system and brain, cancer in hepatobiliary tract and rectum, cancer in the intestines or small bowel as well as endometrial and ovarian cancer and other types of malignancies. Being and extremely under-diagnosed condition, researchers doubt that due to lack of vivid signs and symptoms the frequency of diagnosis of Lynch Syndrome is quite low than its actual occurrence. The best thing about Lynch Syndrome is that it is not cancer itself; rather it predisposes the person to have cancer. Hence, if diagnosed early, the occurrence of cancer can be prevented by various ways.

What is Lynch Syndrome?

What is Lynch Syndrome?

Lynch syndrome or hereditary nonpolyposis colorectal cancer, is an inherited condition or disorder that leads a person towards an increased risk of developing cancer. In this condition, the risk of developing cancer in the liver, urinary tract, small intestine, stomach, gallbladder ducts – in short, colorectal cancer as well as cancer in brain and skin, is increased. In case of women, who suffer from Lynch Syndrome, the risk of growing cancer in the lining of uterus as well as ovaries is increased. In some cases, people with Lynch Syndrome, do not suffer from cancer; but develop non-cancerous or benign growths known as polyps.

Signs and Symptoms of Lynch Syndrome

Lynch syndrome does not have any symptoms or signs as such. It is an inherited condition in itself. This means that the person will have an increased risk of developing womb or bowel cancer. Occurrence of colon cancer before the age of 50 is a strong possibility for people with Lynch Syndrome.

The signs and symptoms associated with possible development of colon cancer are –

  • Bloody stool pass
  • Sudden and unexplained weight loss
  • Constipation or diarrhea without any obvious or known reason
  • Feeling of unclear bowel movement
  • Pain in back passage and tummy

Women with Lynch Syndrome will have the possibility of growing uterine cancer. The possible symptoms in that case are –

Causes and Inheritance of Lynch Syndrome

Lynch Syndrome is an inherited autosomal dominant pattern disorder. This means that the person with this syndrome will have a copy of the altered gene that will increase the risk of developing cancer. Lynch Syndrome is the increased risk of cancer, not the cancer itself. The genes that are associated with this are EPCAM, MLH1, MSH6, MSH2 or PMS2. The children acquire this syndrome from their parents when either or both of their parents have Lynch Syndrome.

In case one of the parents has Lynch Syndrome, the risk of the child inheriting it is 50%. This is because, the child will have one gene inherited from the mother and other from the father, for its cell. Based on the autosomal dominant inheritance pattern of the genes, only one copy undergoes the mutation and the other stays normal. Hence, if the normal gene is inherited by the child, he or she will not acquire or inherit the syndrome. However, if the child inherits the copy of the gene that has undergone mutation, he or she will inherit the syndrome.

Pathophysiology of Lynch Syndrome

The mechanism is simple. Every cell within the body contains genes and these genes contain DNA that carries information regarding the chemical procedures taking place within the body. During cell division, these DNAs also divide and grow. However, in this procedure, it might happen that some minor mistakes take place. The cells are mechanised to recognise the mistake and repair it. In case of Lynch Syndrome, the genes that have undergone mutation and are hence unable to identify and repair the mistake, are inherited by the person. As a consequence, the cells become malignant and continue dividing constantly, leading to cancer.

Risk Factors of Lynch Syndrome

Lynch Syndrome has no gender, ethnic or geographical biasness. The risk factors that are associated with this syndrome are –

  • Children, who have a parent with Lynch Syndrome, will have a 50% increased risk of inheriting this syndrome.
  • Lynch Syndrome has an 85% increased risk of developing colon, endometrial cancer, cancer of gastric tract, pancreas, stomach, brain, breast, skin, hepatobiliary tract, kidney/ureter tract, small intestine, ovaries, prostate and gallbladder duct.
  • Women have a 40%–60% increased risk of developing uterine cancer.

Epidemiology of Lynch Syndrome

Every year, alone in the United States of America, 47,000 new cases of endometrial cancer and more than 140,000 new cases of colorectal cancer are diagnosed. 2% to 5% of endometrial cancers that occur in women and 2% to 4% of all colorectal cancers amongst the above mentioned data are caused by Lynch Syndrome. It is also estimated that about 1 million people in the USA have Lynch Syndrome. This huge number clarifies that the syndrome is not an uncommon or rare one. However, as only 5% of all the cases of Lynch Syndrome are diagnosed, it can be said that it is an extremely undiagnosed syndrome. The number is also huge in Asian countries, with a huge number of 19,570 new cases of colorectal cancer were diagnosed in the year 2006 which occurred due to Lynch Syndrome.

Diagnosis of Lynch Syndrome

In case you encounter the signs and symptoms or possibility of developing colon cancer or if you are suspected to have Lynch syndrome, your doctor will start with asking you about your family history.

  • Family history to diagnose presence of Lynch Syndrome in the family:

The doctor will ask you, if anyone in your family has had colon cancer or any other type of cancer in the past. If they have had it at a young age, it will alert the doctor that your family members might have had this syndrome in their genes. In this regard, the type of cancer, the age of being affected by cancer and the number of generations in the family, who had had cancers, would be considered by the doctor. If more than one family member has had Lynch related tumours in stomach, kidney, ovaries, liver, endometrium or even brain, it would be noted by the doctor.

  • Tumour testing to diagnose Lynch Syndrome:

If someone in the family is diagnosed with cancer, the doctor will take a tissue sample from his or her tumour. Even if members from the family were diagnosed with cancer in the past, the doctor will ask for tissue sample to be supplied by the hospital. These samples are preserved by the hospitals for years. The doctor will run a tumour testing to check if the cancer was caused by genes associated with Lynch Syndrome.

The test can be done in two ways – with IHC or Immunohistochemistry testing and with MSI or Microsatellite instability testing. In IHC testing, the doctor will use special dyes in order to stain the sample tissue. The staining pattern, presence or absence of the dye will indicate the presence of certain proteins and certain missing proteins. This will clearly indicate the presence of mutated genes. The MSI testing finds out the instability of the cellular DNA sequence, known as microsatellites. This will indicate that the tumours are Lynch tumours or not.

  • Genetic testing for detecting Lynch Syndrome:

This test indicates the mutations taking place in your genes. A positive result may indicate that you have Lynch Syndrome. However, it does not mean that you will develop cancer. It indicates that you have developed a lifetime risk of being diagnosed with cancer at any point of time. The genetic testing can even be negative which is very misleading. This is because, if your family members have had Lynch Syndrome and you are not diagnosed with one, it will not show how much you are likely to develop cancer. In fact, if you are the first one in your family to have Lynch Syndrome and still remain misdiagnosed, it will risk the next generations.

Treatment for Lynch Syndrome

The treatment for colon cancers associated with Lynch Syndrome is very similar to that of the colon cancer under general conditions. However, since the patients with this syndrome are always more likely to develop colon cancer, the doctors surgically remove the colon or ovaries as a prevention for further growth of the cancer in colon.

  • Screening of the Cancers in Patients with Lynch Syndrome

Screening of cancer or pre-diagnosing the possibility or presence of pre-cancerous cells and growths, is the first step of treatment. Which particular screening is most suitable for patients with this syndrome is not clear. Hence, the doctor runs multiple screenings.

  • Screening for Colon Cancers: The doctor will run colonoscopy, to check the presence of any cancerous polyp in the colon. The procedure starts from an early age of 20 and done once in every year. If any polyp is found, the doctor will remove it. More intensive Chromoendoscopy technique is used to detect the difficult to detect, flatter polyps in the colon. The doctor uses dyes to test the colon tissue.
  • Screening for Ovarian Cancer: Women, who have Lynch Syndrome and are in their 30s, also have to undergo an annual ovarian cancer screening.
  • Screening for Endometrial and Uterine Cancer: Annual endometrial biopsy or ultrasound screening is done on women, who have Lynch Syndrome and are in their 30s.
  • Screening for Urinary System Cancer: Urinary system cancer screening is also occasionally done to check if any cancerous cells or blood traces are found in urine.
  • Screening for Gastrointestinal Cancer: To check the possibility of cancer in gastrointestinal system, the doctor will run screening in the stomach and small intestine.

The cancers caused due to Lynch Syndrome can be prevented by surgically removing the colon, uterus and ovaries.

Although, Lynch Syndrome can be prevented, with proper screening and diagnosis, it becomes easier to tackle the condition so that it does not worsen. Removal of colon and ovaries is a great preventive measure to keep cancer at bay. Screening regularly will also help in early diagnosis and the life span also increases.

Pramod Kerkar, M.D., FFARCSI, DA
Pramod Kerkar, M.D., FFARCSI, DA
Written, Edited or Reviewed By: Pramod Kerkar, M.D., FFARCSI, DA Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:January 28, 2019

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