Lynch syndrome, named after Dr. Henry Lynch, is a form of inherited colon cancer which usually presents with a few to less than 50 polyps. The primary cancers of concern in Lynch syndrome are colon and endometrial (uterine) but other forms of cancer have been linked as well, usually with low lifetime risks. Lynch syndrome represents a spectrum of disease, with lifetime cancer risks being different based on which of the four Lynch syndrome genes are mutated. The four genes in question are MLH1, MSH2, MSH6, and PMS2, and when these genes are able to work properly, they come together in the cell to stop cancer from developing. In Lynch syndrome, one of these genes is unable to function normally. In general, mutations in MLH1 and MSH2 cause higher risks for cancer than MSH6 or PMS2.
If a person has had a cancer that is related to Lynch syndrome, their doctor may order a test called either Microsatellite Instability (MSI) or Immunohistochemistry (IHC) on the tumor itself. This testing can tell us if the Lynch syndrome genes in the tumor are working the way they are meant to. Oftentimes, the genes in a tumor will show problems that we don’t see throughout the body; this is called somatic mutation. If the genes in a tumor are broken, we would then have to check a person’s genes that are not in the tumor to see if the mutation is somatic or not. Finding a problem on MSI or IHC is a typical warning sign on Lynch syndrome, but is not a confirmation without further testing. Sometimes these studies will show a problem with MLH1 and possibly PMS2, that can be cause by what is called MLH1 hypermethylation. Methylation is a process the cell uses to turn things off, so MLH1 hypermethylation happens when the cell turns MLH1 off completely or almost completely. We cannot know for certain without testing MLH1 for hypermethylation, but this event is thought of as sporadic and is not a diagnosis of Lynch syndrome.
Lynch syndrome is inherited as an autosomal dominant condition. This means that each child of an individual having one of these gene mutations has a 50 percent chance themselves of inheriting the mutation. Genetic testing is available which can identify mutations in many, but not all, families with hereditary colon cancer. If a mutation is identified in an affected individual in a family, at-risk family members can be tested. Those relatives inheriting the mutation face increased cancer risks, and should be followed appropriately. Relatives who have not inherited the gene mutation are at no increased risk for cancer over the general population.
Guidelines for patients with Lynch syndrome call for colonoscopy every 1 to 2 years starting at age 25 (or 5 years before the earliest colon cancer diagnosis in family, if it was under age 30). While no one screening method for endometrial cancer has been shown to be particularly effective, some women may consider a hysterectomy (surgical removal of the uterus) and all women should be offered an endometrial biopsy every 1-2 years. All other cancers associated with Lynch syndrome should be screened for on an individual basis in light of personal and family history.