SNP Shot: Genomic Insights

Familial adenomatous polyposis (FAP) is an inherited condition predisposing individuals to colorectal cancer. The classic form of FAP is characterized by the development of numerous benign polyps in the colon and rectum, often starting in the teenage years. Without colon removal, these polyps inevitably progress to cancer. The average age of colon cancer diagnosis in classic FAP is around 39. A less aggressive form, attenuated FAP, features a delayed onset of polyp growth and a later average age of colorectal cancer diagnosis, around 55.

In classic FAP, the number of polyps increases with age, potentially reaching into the thousands. Another significant complication is the development of desmoid tumors, which are noncancerous fibrous growths typically found in the tissue lining the intestines. These tumors can be triggered by colon removal surgery and have a tendency to recur after surgical removal. Both classic and attenuated FAP can sometimes involve the development of both benign and cancerous tumors in other areas of the body, such as the duodenum, stomach, bones, skin, and other tissues. The presence of colon polyps along with growths outside the colon is sometimes referred to as Gardner syndrome.

A milder form of FAP, known as autosomal recessive familial adenomatous polyposis, exists. Individuals with this type develop fewer polyps compared to those with classic FAP, typically less than 100. This form is caused by mutations in a different gene than the classic and attenuated forms.

Inheritance:

FAP can be inherited in different ways depending on the affected gene. When FAP is caused by mutations in the APC gene, it follows an autosomal dominant inheritance pattern. This means only one copy of the mutated gene is needed to cause the condition. In most cases, a person with APC-related FAP has an affected parent. When FAP results from mutations in the MUTYH gene, it follows an autosomal recessive inheritance pattern. This means that two copies of the mutated gene are needed to cause the condition. Typically, the parents of someone with MUTYH-related FAP each carry one copy of the mutated gene but do not exhibit symptoms of the condition themselves.