Colon Cancer Risk
Every man and woman has a risk to develop colon cancer during their lifetime. The estimated general population lifetime risk for colorectal cancer is four to five percent, affecting approximately one in every 20 people. Most colon cancers happen by chance. However, some families have an inherited predisposition to colon cancer.
Researchers have identified two main forms of hereditary colon cancer:
- Familial adenomatous polyposis (FAP) , representing less than one percent of all colorectal cancer cases diagnosed each year
- Hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch syndrome, representing about five percent of cases.
We become more suspicious of a hereditary cause to cancer in a family if individuals:
- are diagnosed with colon cancer at young ages (age 50 or younger);
- have multiple family members with colon or related cancers (uterine cancer, ovarian cancer, cancers of the upper GI or urinary systems);
- have multiple polyps in their colon.
Lynch Syndrome Overview
Lynch syndrome is a hereditary colon cancer syndrome that is associated with a significantly increased risk to develop colon cancer and uterine cancer, and a smaller increased risk to develop cancers of the stomach, ovaries, hepatobiliary tract, urinary tract, small bowel, and brain/central nervous system.
Families with Lynch syndrome often have multiple individuals affected with colon cancer or other related Lynch syndrome cancers on one side of the family. We can also see individuals diagnosed with cancer at younger ages and multiple primary cancers in one individual.
There are several genes associated with Lynch syndrome including MLH1, MSH2, MSH6, PMS2 and EPCAM. These genes are called “mismatch repair” genes. Mutations in these mismatch repair genes are inherited in an autosomal dominant pattern. This means that an individual with Lynch syndrome has a 50 percent (one in two) chance of passing the genetic mutation causing Lynch syndrome on to each one of his or her children.
Some families have Lynch syndrome, but do not a have an identifiable mutation in any of the above genes. A clinical diagnosis of Lynch syndrome can be made in a family based on:
- The types of cancer seen in a family
- The ages those cancers were diagnosed
- How those diagnosed with cancer are related to each other
Polyposis Syndromes Overview
Familial Adenomatous Polyposis (FAP) and Attenuated FAP (AFAP) are two hereditary cancer syndromes associated with a predisposition to develop colon polyps (growths that form from the inner lining of the colon, or large intestine) and an increased risk for colon cancer.
Polyps are generally benign. However, some colon polyps can turn into cancer if they are not removed. A specific type of polyp, known as an adenomatous polyp (or adenoma), is more likely to develop into cancer than other polyps. Most colon polyps develop after the age of 50 and are removed at the time of routine colonoscopy.
Individuals with familial adenomatous polyposis (FAP) develop multiple adenomatous (pre-cancerous) polyps in the gastrointestinal tract. 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 and older age.
Polyps are mostly found in the colon and rectum but can also be found in the small intestines, stomach, and other areas. On average, colorectal polyps in someone with FAP begin to appear in the late teens. Without careful surveillance and/or intervention, the risk for colon cancer is 100 percent. The other cancer risks seen in FAP include small bowel, pancreatic, thyroid, liver, and bile duct cancer; the risk for each these is significantly lower than the risk for colorectal cancer. Individuals with FAP are also at risk for specific non-cancerous findings, including changes in the eyes, skin, and teeth.
FAP is caused by genetic mutations in the APC gene. APC mutations are inherited in an autosomal dominant pattern. An individual with FAP has a 50 percent (one in two) chance of passing the genetic mutation causing FAP on to each one of his or her children. Although most people with FAP have a family history of colon polyps and/or cancer, 20 to 25 percent of individuals with FAP do not have any family history. This is because 20 to 25 percent 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, he or she can pass the mutation on to their children.
MUTYH-associated polyposis (MAP) is another hereditary syndrome that leads to the development of many adenomatous polyps in the colon. MAP typically presents like attenuated FAP, with less than 100 colon polyps and an older age of onset. However, some individuals may have more or less polyps than typically seen with AFAP.
People with MAP have a 43 to 100 percent risk to develop colon cancer without careful surveillance and/or intervention. Because MAP is a relatively newly discovered hereditary polyposis syndrome, the risk for polyps and cancer outside of the colon is unclear. Researchers are working to further define these risks.
MAP is caused by genetic mutations in the MUTYH gene (sometimes also called MYH). MUTYH mutations are inherited in an autosomal recessive pattern. This means that in order to have MAP, you must inherit a 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 two individuals are both “carriers” of MYH mutations, each of their children would have a 25 percent chance to have MAP.
Other genes associated with hereditary risk for colon cancer and colon polyps have been more recently discovered and are available as part of Next Generation Sequencing technology.