Lynch Syndrome

 
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What is Lynch Syndrome:

Lynch Syndrome is an inherited or hereditary cancer syndrome that increases the risk of certain cancers, especially colorectal cancer. It is also known as hereditary non-polyposis colorectal cancer (HNPCC). 

What causes Lynch Syndrome:

The inherited disorder is caused by a mutation in a mismatch repair gene.  Genes identified within this syndrome are termed mismatch repair genes (MLH1, MSH2, MSH6, PMS2) as they function to identify cellular mistakes made during replication and repair them.  All cells replicate and when inevitable mistakes are made, cells are able to use this mismatch repair gene to correct the mistake. When there is a genetic mutation, or an inherited abnormality within one of the associated mismatch repair genes, the cells are not able to perform their normal function of repairing cellular. Over time, accumulation of cellular damage that is not repaired can lead to cancer formation. 

What cancers are associated with Lynch Syndrome:

Lynch syndrome is the most common inherited disorder that increases the risk of colorectal and endometrial (uterine) cancer. About 3-5% of all colorectal cancers and 2-3% of all endometrial cancers are associated with Lynch syndrome.  Cancer may present earlier than expected in individuals affected by hereditary cancer syndromes such as Lynch Syndrome. 

Other associated cancers with Lynch syndrome may include elevated risk of colorectal cancer, endometrial (uterine) cancer, ovarian cancer, pancreatic cancer, stomach cancer, small intestinal cancer, kidney cancer, brain cancer, skin cancer.  Rates of breast and prostate cancer may also be elevated in Lynch Syndrome but the research is not sufficient at this time to declare a direct relationship.

Rates of colorectal cancer can be increased as high as 20-80% lifetime risk of developing colorectal cancer in individuals that carry a mutation in one of the associated genes.  Cancer rates vary depending on the gene that is affected. Not everyone who has Lynch syndrome will develop cancer but know that their risk is elevated from the general population for the cancers listed above. 

How is Lynch Syndrome identified:

Genetic mutations can be identified by sequencing DNA with a blood sample looking at what is called the “germline DNA” or DNA that you inherited and were born with. The blood test is sent off to a specialty lab that sequences the DNA looking for a genetic change associated with Lynch Syndrome.  Genetic mutations can also be found in the tumor after surgical removal and may then need to be confirmed by germline DNA testing described above. 

How is Lynch syndrome inherited:

Lynch syndrome runs in families.  When a genetic mutation is identified and Lynch syndrome is diagnosed, other family members are at increased risk for also having Lynch syndrome and subsequently an increased risk for developing the associated cancers. Lynch syndrome is inherited in an autosomal dominant pattern. This means you only need one copy of the abnormal gene to have the associated increased risk of cancer.  This also means that first degree family members of individuals affected by Lynch Syndrome have a 50% chance of also carrying the abnormal genetic change. When individuals are diagnosed with Lynch syndromes, other family members, especially first degree relatives (parents, siblings and children) should also be tested. 

Genetic testing is performed on a simple blood test and is covered by insurance in individuals that qualify for testing. If identified, increased cancer screening can be instituted to identify cancer early.  Although we cannot change our genetic makeup, identify cancer early can reduce the necessary treatment for cancer and reduce the risk of death from cancer. 

Who should be considered for genetic testing:

Genetic counseling and discussion of genetic testing should be considered in individuals that:

~ are diagnosed with colorectal cancer at age 50 or less

~ are diagnosed with endometrial cancer at age 50 or less

~ has been diagnosed with 2 separate Lynch syndrome associated cancers

~ has a family member with a known genetic mutation

~ have a family history of colorectal cancer at an early age (50 or less) especially in a first degree relative

~ have multiple family members with colorectal cancer

~ have multiple family members with endometrial cancer, especially at early age 

~ have a family of ovarian cancer

~ have a family history of pancreatic cancer