How is Lynch syndrome inherited?
We all have two copies of every gene, including two copies each of MLH1, MSH2, MSH6, PMS2, and EPCAM. We inherit one copy of each gene from our mother and one copy from our father. When working properly the MLH1, MSH2, MSH6, PMS2, and EPCAM genes help to reduce cancer risk. People with Lynch syndrome have a gene change (mutation) in one of their MLH1, MSH2, MSH6, PMS2, or EPCAM genes that cause the gene not to work properly. A non-working copy of the gene leads to increased risk for cancer. If a parent has Lynch syndrome, there is a 50% chance that each of his or her children will also have Lynch syndrome. This is called autosomal dominant inheritance.
- Kohlmann W, Gruber SB. Lynch Syndrome. 2004 Feb 5 [Updated 2018 Apr 12]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1211/
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What does it mean to have a "variant of uncertain significance" for Lynch syndrome?
Sometimes genetic testing shows a change in the MLH1, MSH2, MSH6, PMS2, or EPCAM genes called a “variant of unknown significance” or a VUS. This means that a genetic change was found that we do not fully understand. In other words, this genetic change may cause Lynch syndrome or it may be normal variation. We need more data to be sure. A genetic counselor or geneticist can help explain what this result means. Over time, scientists may learn more about variants of unknown significance. If someone has a VUS in a Lynch syndrome gene they should check with their healthcare provider on an annual basis for updates on the VUS.