What is Lynch Syndrome?

Inherited gene mutations, such as BRCA 1 and BRCA 2, can increase the risk of developing ovarian cancer as well as uterine (endometrial) cancer. Some of these mutations, which affect MLH1, MSH2, MSH6, PMS2 and EPCAM genes, can cause Lynch Syndrome. This disorder is also called hereditary non-polyposis colorectal cancer (HNPCC) and, as its name suggests, it can lead to various cancers (ovarian cancer among them).

How does Lynch Syndrome cause cancer?

Lynch Syndrome’s connection to cancer starts with those inherited changes to the MLH1, MSH2, MSH6, PMS2 or EPCAM genes. Though everyone has two copies of each of these genes—one inherited from your biological mother and one inherited from your biological father—it takes just one hereditary gene variant to cause Lynch Syndrome. It is estimated that one out of every 279 people in the United States has a gene mutation associated with Lynch Syndrome.

These variants are passed down in an autosomal dominant inheritance pattern, meaning that there is a 50% chance that if one parent has the mutation, the child will get it as well. The variant is not specific to gender; it is equally likely that either parent can have the Lynch Syndrome mutation and pass it down to a biological daughter and/or son. This type of inherited genetic variance is also called a germline mutation because it is present in the sperm or egg cells, which are also known as germ cells. And when the child inherits the variance, that genetic change exists in virtually every single cell of the body from birth. 

Most of the genes that can be affected by a Lynch Syndrome mutation are supposed to regulate DNA mismatch repair. Meaning, they are critical to the process of fixing any mistakes that may occur when the body copies DNA. It’s not unusual for minor mistakes to occur when DNA is replicated, which happens every time a cell divides (nearly 2 trillion times a day). But when a mutated gene is unable to correct those mistakes in the DNA, the abnormalities continue to spread as the cells continue to divide, which can then lead to cancer. 

The connection between Lynch Syndrome and ovarian cancer

Since the specific genetic mutations associated with Lynch Syndrome are found in nearly every cell throughout the body, they can cause a number of different cancers to develop, with ovarian cancer being among the possibilities. Women, as well as trans men and nonbinary people, are at greater risk of getting ovarian cancer if they carry the Lynch Syndrome gene variant.  

Lynch Syndrome-associated ovarian cancer is typically diagnosed before the age of 50. The mean age of diagnosis is between 43 and 46 years, according to information published by the National Center for Biotechnology Information (NCBI), a center within the U.S. National Library of Medicine at the National Institutes of Health. 

Females who have the inherited MLH1, MSH2, or MSH6 gene mutation associated with Lynch Syndrome have an 11% – 17% risk of developing ovarian cancer by age 70, according to the NCBI data. However, women with a germline PMS2 genetic variant have a relatively low increased likelihood of getting ovarian cancer, with a 3% risk associated with that specific mutation. 

What cancers are related to Lynch Syndrome?

In addition to its connection to ovarian cancer, Lynch Syndrome is also linked to a higher likelihood of developing another type of cancer that is specific to women. Research shows that having a Lynch Syndrome mutation can cause a greater propensity for getting endometrial cancer (also called uterine cancer). The risk varies depending on which gene is affected, but the chance of developing it by age 70 can be as high as 46%.  

People living with Lynch Syndrome also have a higher risk of developing cancers of the colon and rectum (collectively referred to as colorectal cancer or CRC). The risk for getting colorectal cancer by age 70 can be as high as 75% , depending on which genetic mutation they carry. Lynch Syndrome is also linked to cancers of the stomach, small bowel, urinary tract, biliary tract, brain, skin, pancreas, and prostate.

Can you have Lynch Syndrome and not get cancer?

It’s important to note that what is passed down in families with Lynch Syndrome is the gene mutation, not cancer. And not everyone who inherits the mutation will develop cancer.

Typically, this gene variant is passed down from just one parent and not both. And since genes always come in pairs, the child will also likely inherit a normal gene that is not mutated. Cancer would generally only occur if this normal gene that works properly becomes affected by a second mutation at some point. Unlike the inherited Lynch Syndrome gene variant, this second mutation would not be found in every cell of the body, but only in the cancerous tissue.

What are the symptoms of Lynch Syndrome?

Since Lynch Syndrome does not always cause cancer, many people who inherit a Lynch-related gene mutation do not know that they have the disorder.   

The best way to determine if you may have Lynch Syndrome is by discussing your own medical history and your family’s medical history with your doctor. Signs that you may have this disorder include a personal or family history of colorectal or endometrial cancer before the age of 50.  Your doctor may refer you to a genetic counselor to further explore if genetic testing is right for you.

Who should get tested for Lynch Syndrome?

Lynch Syndrome can be diagnosed via a blood test that detects if you have one of the gene mutations that causes this disorder. This type of genetic testing is typically recommended if you have a family member who has already been diagnosed with Lynch Syndrome or a few family members who have developed cancers associated with Lynch Syndrome. 

Testing is also advised if you have received certain types of cancer diagnoses, which may include the following: endometrial or uterine cancer before age 50, colorectal cancer, or multiple primary cancer diagnoses. Additionally, guidelines from the Society of Gynecologic Oncology state that everyone diagnosed with ovarian cancer should undergo genetic testing.  

You may also be sent for genetic testing as a cancer patient if specific screening tests have been performed on your tumor and determined that you likely have Lynch Syndrome. These screening tests are known as microsatellite instability testing (MSI) and immunohistochemistry testing (IHC).

Learn more about genetic testing.

Information about other gene mutations that can also cause ovarian cancer can be found here.

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