Gastrointestinal Cancer Genetic Testing

Lynch syndrome is a hereditary colorectal cancer syndrome that is linked to a significantly increased risk of developing colorectal cancer and uterine cancer. Those with Lynch syndrome also have a slightly elevated risk of developing the following types of cancers: ovarian cancer, stomach cancer, small bowel cancer, cancer of the pancreas or hepatobiliary tract, cancer of the urinary tract, skin cancers and brain or central nervous system cancer.

Families with Lynch syndrome often have multiple individuals affected with colorectal cancer or other related Lynch syndrome cancers on one side of the family. We also see individuals diagnosed with cancer at younger ages and multiple primary cancers (cancer that starts in more than one area of the body).

There are several genes associated with Lynch syndrome:

The above genes are called mismatch repair (MMR) genes. A person inherits mutations in these mismatch repair genes in an autosomal dominant pattern. This means inheriting one copy of the mutated gene from either parent is enough to increase the risk of developing cancer. If you test positive for one of these MMR genes, then each first-degree relative (parents, siblings and biological children) would have a 50% chance to have this same genetic mutation.

Some families have Lynch syndrome but don’t have an identifiable mutation in any of the associated genes.

Individuals with FAP develop multiple adenomatous (pre-cancerous) polyps in the GI tract at younger ages. Individuals with classic FAP may develop hundreds to thousands of adenomatous polyps. Individuals with the attenuated form of FAP develop fewer polyps and often develop polyps at later ages.

Polyps are mostly in the colon and rectum, but they can form in the small intestines, stomach and other areas. On average, colorectal polyps in someone with FAP begin to appear in the late teen years. Without careful surveillance and/or intervention, the cumulative risk for colon cancer approaches 100%. Those with FAP also have a slightly elevated risk of developing the following types of cancers:

Individuals with FAP also are at risk for specific non-cancerous issues, including changes in the eyes, skin and teeth. 

FAP is caused by genetic mutations in the APC gene. A person inherits APC mutations in an autosomal dominant pattern. An individual with FAP has a 50% chance of passing on this genetic mutation to each one of his or her children.

Although most people with FAP have a family history of colon polyps and/or cancer, 20–25% don’t have any family history. This is because 20–30% of the time, an APC mutation is new in that person and not inherited from a parent. However, once an individual has an APC mutation, they can pass on the mutation to their children.

This is another hereditary cancer syndrome that leads to the development of many adenomatous polyps in the colon. MAP typically causes similar symptoms as attenuated FAP, with fewer than 100 colon polyps and an older age of onset. However, some people may have more polyps — or fewer polyps — than typically seen with AFAP.

People with MAP have a 70-90% risk to develop colon cancer without careful surveillance and/or intervention. There is an increased risk for polyps and cancers to develop outside of the colon, particularly in the duodenum (duodenal polyps, 17-34%, and duodenal cancer, 4%). Researchers are working to further define these risks. 

MAP is caused by genetic mutations in the MUTYH gene. A person inherits two MUTYH mutations in an autosomal recessive pattern. This means that to have MAP, you must inherit one genetic mutation in MUTYH from each parent.

An individual with only one mutation in the MUTYH gene is a carrier for MAP and generally not thought to be at a significantly increased risk for cancer. If both parents are carriers of MUTYH mutations, their children would each have a 25% chance of having MAP.