The following rare syndromes also increase the risk for colorectal cancer:
Turcot syndrome. This is a rare disorder that includes colorectal polyposis, colon cancer, and brain tumors. Mutations in different genes have been found in individuals with this syndrome, including mutations in the APC, MLH1, and PMS2 genes. For this reason, Turcot syndrome is said to be genetically heterogeneous.
Peutz-Jeghers syndrome (PJS). Peutz-Jeghers syndrome is an autosomal dominant disorder that is associated with the following characteristics:
Melanocytic macules (dark blue or brown moles)These moles can be located around and/or in the mouth including the lips, and around the eyes, nostrils, and anus. Dark moles may also appear on the fingers. The lesions may fade by adulthood.
Multiple polyps in the gastrointestinal tract
Increased risk for benign (noncancerous) tumors of the ovaries and testes
Increased risk of cancers of the stomach, small intestine, breast, ovaries, colon, and pancreas
Peutz-Jeghers syndrome is caused by mutations in a gene on chromosome 19 known as STK11, which functions as a tumor suppressor gene.
Familial colorectal cancer (FCC). Up to 15 percent of colorectal cancer patients have family members with colorectal cancer, but do not have a known colorectal cancer syndrome, such as familial adenomatous polyposis (FAP) or hereditary nonpolyposis colon cancer. Colon cancer in these families may appear to follow an autosomal dominant pattern of inheritance. As genetic research continues, genes may be identified to explain these family histories.
Juvenile polyposis syndrome. This rare, childhood-onset disease is an autosomal dominant disorder that results from mutations in various cancer susceptibility genes, including the SMAD4/DPC4 and BMPR1A genes. The condition is associated with the development of hamartomatous polyps (few to numerous) that can be present throughout the gastrointestinal tract. Other symptoms can include diarrhea, hemorrhage, and protein-losing enteropathy. Juvenile polyposis is associated with an increased chance for gastrointestinal and pancreatic cancers. Most patients appear to be sporadic cases (happening for the first time in a family). However, this may actually be the result of decreased penetrance (for example, the causative gene mutation is present in one of the parents but the symptoms did not develop).
MYH-associated polyposis (MAP). Mutations in the MYH gene increase the chance for an individual to develop multiple colorectal polyps or colorectal cancer. Unlike most polyposis and colorectal cancer disorders, MAP is considered to be an autosomal recessive disorder. This means that individuals with MAP have mutations in both copies of their MYH gene.
The number of polyps in individuals with MAP can range from a few to hundreds. The symptoms of MAP overlap with both FAP and attenuated FAP. Genetic testing for mutations in the MYH gene is available and should be considered in individuals suspected of having FAP or attenuated FAP who do not have a mutation in the APC gene. It is not currently known if individuals with only one MYH mutation have a higher than average risk for colorectal polyps and cancer.