Lynch Syndrome

What is Lynch Syndrome?

Lynch syndrome is a mutation of a gene that is responsible for fixing errors in your DNA.

Lynch Syndrome is caused by a genetic mutation that increases a person’s risk for certain cancers. One in every 440 Americans has Lynch Syndrome, but the majority of these people have not been diagnosed. A doctor can estimate a person’s risk of having Lynch Syndrome based on their family history of cancer. A blood test can confirm the diagnosis. To prevent colorectal cancer, people with Lynch Syndrome should undergo a colonoscopy every 1-2 years, starting in their twenties. They may also consider taking aspirin every day.

The human body is always creating new cells. Every time your body makes a new cell, it must copy your genes. There is always a chance that a “typo” will pop up in the new copy. In other words, the DNA for the new cell will not look quite like the DNA from the original cell. These DNA copying errors can affect the way a cell grows, and may lead to cancer. Usually, a gene called the DNA mismatch repair gene (MMR for short) looks out for these mistakes and fixes them before they damage the cell.

People with Lynch syndrome have a mutation of the MMR gene, which means their bodies are less able to fix errors in the DNA. This means that a person with Lynch syndrome is more likely to get certain types of cancer. Lynch syndrome increases the risk of getting colorectal cancer by 80 percent and endometrial cancer by 60 percent. Lynch syndrome can also lead to other cancers, including:

 

  • Cancers of the stomach and small intestine.
  • Cancer of the pancreas.
  • Cancer of the urinary tract, including kidneys.
  • Cancer of the bile ducts.
  • Sebaceous (oil) gland tumors.
  • Ovarian cancer.
  • Skin cancer.
  • Glioblastoma multiforme (a type of brain cancer).

Most people with Lynch syndrome do not know they have it.

Lynch syndrome is the most common inherited cause of colorectal cancer. About one in every 440 people, or around 725,000 Americans, have Lynch syndrome. The child of a person with Lynch syndrome has a 50 percent chance of inheriting it. However, the majority of people with Lynch syndrome do not know they have it.

Your doctor can use your family history to estimate your risk.

Your doctor can use a risk prediction model to estimate the chance that you have Lynch syndrome. To estimate your risk, your doctor will need to know the following things:

  • Whether you have ever had cancer, and what type(s).
  • The approximate age at which each family member was first diagnosed with cancer.

Based on this information, your doctor may decide to refer you to a genetic counselor or to order a genetic test. This test uses a small amount of your blood to look for the mutations that cause Lynch syndrome.

You may already know that a family member has Lynch syndrome. If so, tell your doctor. If your relative has already had a genetic test, bringing those results to your doctor can make it easier to find out whether you, too, have Lynch syndrome.

If you have a strong family history of cancer, consider asking your doctor these questions:

  • With my family history of cancer, am I at risk for having Lynch Syndrome?
  • If so, would you recommend that I get a genetic test done or see a genetic counselor? 
  • What are the risks and benefits of genetic testing?

How to Prevent Colorectal Cancer if You Have Lynch Syndrome

Get a colonoscopy every 1 to 2 years, starting in your twenties.

If you have Lynch syndrome, you should get a colonoscopy every one to two years to screen for colorectal cancer. Doing this will reduce your risk of colorectal cancer by 77 percent. 

Exactly when should you get your first screening?

Find out the youngest age at which a family member first got colorectal cancer. Then, follow these guidelines:

  • If that person was younger than 25 when they were first diagnosed: subtract five from that age. For instance: if they were 24 at the time of diagnosis, get your first colonoscopy at 19.
  • If that person was 25 or older when they were first diagnosed: start between the ages of 20 and 25.

Remember, most people with Lynch syndrome do not know they have it. If you have Lynch syndrome, the most important thing to do is start getting screened as soon as possible to keep yourself healthy.

Talk to your doctor about taking aspirin every day.

Taking 600 milligrams of aspirin every day may decrease your odds of getting colorectal cancer by 44 percent. 

The ideal dosage of aspirin is not known, and there are risks from taking aspirin at such a high dose. Some people, such as those with stomach bleeding or blood clotting disorders, should not take aspirin regularly. Talk to your doctor to decide whether and how much aspirin to take. Taking aspirin should not replace getting a colonoscopy every one to two years.

If you are diagnosed with Lynch Syndrome, prepare to ask your doctor the following questions:

  • How do I schedule and prepare for a colonoscopy?
  • How can I make sure I remember to schedule a colonoscopy every one to two years?
  • Would it be safe for me to take 600 milligrams of aspirin per day to reduce my risk of colorectal cancer?

Reference1

 

What are the types of Gene Mutations?

Variations in the MLH1, MSH2, MSH6, PMS2, or EPCAM gene increase the risk of developing Lynch syndrome.

The MLH1, MSH2, MSH6, and PMS2 genes are involved in the repair of mistakes that occur when DNA is copied in preparation for cell division (a process called DNA replication). Mutations in any of these genes prevent the proper repair of DNA replication mistakes. As the abnormal cells continue to divide, the accumulated mistakes can lead to uncontrolled cell growth and possibly cancer.

Mutations in the EPCAM gene also lead to impaired DNA repair, although the gene is not itself involved in this process. The EPCAM gene lies next to the MSH2 gene on chromosome 2; certain EPCAM gene mutations cause the MSH2 gene to be turned off (inactivated), interrupting DNA repair and leading to accumulated DNA mistakes.

Although mutations in these genes predispose individuals to cancer, not all people who carry these mutations develop cancerous tumors.

 

What are the Risks?

The cancer risks for individuals with Lynch syndrome vary depending on the gene in which their mutation occurs and whether the family was diagnosed in a high risk clinic (higher risks) or through routine screening of cancer patients (lower risks) as shown in the following table. 

Cancer type 

MLH1& MSH2 Mutations 

MSH6 mutations 

PMS2 mutations 

General Public 

Colon (men) 

40-80% 

10-30% 

20% 

5% 

Colon (women) 

40-80% 

10-30% 

15% 

5% 

Endometrial (uterine) 

30-60% 

15-30% 

15% 

2% 

Stomach 

<13% 

< 3% 

6% 

<1% 

Ovarian 

 

12-24% 

1-11% 

6% 

1.5% 

Reference2

1. American Gastroenterological Association, 2015

2. The James, The Ohio State Comprehensive Cancer Center, 2015