Colorectal Cancer: Types of Hereditary Colorectal Cancer

Memorial Sloan Kettering has special expertise in diagnosing and treating the following types of hereditary colorectal cancer.

Familial Adenomatous Polyposis (FAP)

Familial adenomatous polyposis (FAP) is a rare disorder, accounting for less than 1 percent of all colorectal cancers. FAP leads to the development of multiple adenomatous polyps in the colon and rectum, usually beginning in the teen years and increasing in number to the hundreds or even thousands at a young age. People with FAP who are left untreated develop colorectal cancer at a median age of 40, and death occurs at a median age of 44.(1)

FAP is caused by a mutation in the APC gene, which normally prevents the uncontrolled cell growth that leads to cancer. Although most patients with FAP have a family history of the condition, up to 25 percent of FAP cases represent a new mutation.(2) People with a parent with FAP have a 50 percent chance of having FAP themselves. Patients with FAP may also be at risk for polyps in their stomach or small intestine, as well as other types of benign and malignant tumors.

Attentuated Familial Adenomatous Polyposis (AFAP)

Attenuated familial adenomatous polyposis is a milder form of FAP. This syndrome is also caused by a mutation in the APC gene. Patients with AFAP have fewer polyps — less than 100 — and the polyps tend to be smaller and flatter than those present in FAP. Polyps and colorectal cancer occur later in AFAP, at average ages of 44 and 56, respectively. The exact lifetime risk for colorectal cancer in someone with AFAP is unknown at present but is believed to be significantly higher than average.

Lynch Syndrome

Pictured: Kenneth Offit
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Medical experts from Memorial Sloan Kettering discuss Lynch syndrome, a genetic disorder that can cause colon and other cancers.

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Lynch syndrome, also called hereditary nonpolyposis colorectal cancer (HNPCC), accounts for 2 to 3 percent of all colorectal cancers. The disorder typically manifests later in life than FAP but produces a fast-growing cancer that occurs at an average age of 45. Some patients with Lynch syndrome have colorectal polyps beginning at an early age. Others do not develop many polyps but may still develop a colorectal cancer. People with Lynch syndrome have an 80 percent lifetime risk of developing colorectal cancer, and they are also at much higher risk for endometrial, ovarian, stomach, urinary tract, and other cancers.

Lynch syndrome is caused by mutations in one of the four mismatch repair (MMR) genes, which repair mistakes as DNA is copied when the body makes new cells. Only one copy of a mutated form of the gene — which may be inherited from either parent — is necessary for a person to develop Lynch syndrome. Lynch syndrome is often diagnosed at the time that a patient is diagnosed with colorectal cancer. If preliminary testing of a tumor suggests that you have Lynch syndrome, a blood test may be performed for further evaluation. In some cases, FAP or MAP must also be ruled out.

Some patients fit the clinical criteria of Lynch syndrome — a family history of colorectal cancer and lack of FAP and MAP mutation — but are found not to have an MMR mutation. These patients are said to have a disease called familial colorectal cancer type X, which is similar to Lynch syndrome, but is usually diagnosed at a slightly older age. Less is known about this syndrome, but patients seem to have an increased risk of colorectal cancer and possibly other cancers as well.

MYH-Associated Polyposis (MAP)

MYH-associated polyposis (MAP) was only recently identified. It is caused by mutations in the MYH gene. Unlike FAP and AFAP, MAP follows an autosomal recessive inheritance pattern — meaning that a mutation needs to be present in both copies of the MYH gene (that is, from both the mother and father) in order for a person to have the disease. MAP is usually suspected if a person has multiple adenomatous colon polyps but does not have a mutation in the APC gene, or has brothers or sisters with multiple colon polyps but there is no history of colon problems in previous generations. Often, parents do not have polyps because they only have one mutated copy of the gene. Preliminary research suggests that there is a high risk of colorectal cancer with MAP, but the risk of other cancers is not yet known.

Hyperplastic Polyposis Syndrome (HPS)

Hyperplastic polyposis syndrome (HPS) is a rare condition characterized by the development of multiple hyperplastic polyps in the colon and rectum. Hyperplastic polyps are ordinarily smaller than adenomatous polyps, but in people with HPS, these polyps are enlarged and numerous. Although hyperplastic polyps were once considered benign in all cases, it is now known that some may go on to become cancer and that people with HPS are at a significantly increased lifetime risk for developing colorectal cancer — perhaps as high as 40 percent. Additionally, some patients with HPS may also have other types of polyps in their colon in addition to hyperplastic polyps.

Researchers have found evidence of several genetic mutations that might cause HPS, but none has been conclusively identified. Therefore, no genetic test exists for HPS.