Familial Adenomatous Polyposis and Colorectal Cancer

Familial adenomatous polyposis is unlike any other hereditary colorectal cancer. Receiving a cancer diagnosis is already difficult enough, but what more if the patient is a teen or young adult still with much of their life ahead of them? The distress to both the patient and family members is unimaginable.

Whether you are a parent or an individual diagnosed with familial adenomatous polyposis, the disbelief you feel at such an early diagnosis is understandable. You might think, how could one so young possibly get cancer? Rare as it is, familial adenoma polyposis is characterized by its early onset and the 100% likelihood of developing into colorectal cancer if left untreated.

Fortunately, because the syndrome presents itself early in life, it can be acted on early to prevent its development into cancer. While it may be difficult to come to terms with a familial adenomatous polyposis diagnosis, we hope that knowing more about the syndrome and the preventive treatment options can assuage your distress.

Familial adenomatous polyposis (FAP), sometimes referred to as classic familial adenomatous polyposis or familial polyposis coli (FPC), is a genetic condition and the second most common hereditary colorectal cancer. However, it is considered rare — about 1% of all colorectal cancer cases result from FAP.

Mutation in adenomatous polyposis coli (APC) gene

FAP arises as a result of mutations in the adenomatous polyposis coli (APC) gene. APC is a tumor suppressor and also plays an important role in the alignment of chromosomes during metaphase (a stage during cell division).

In the colon when APC is functioning normally without mutations, the APC protein promotes apoptosis — or programmed cell death — of epithelial cells in the colonic lining. As such, the lack of a functioning APC gene prevents apoptosis and results in the uncontrolled growth of cells. This uncontrolled growth is responsible for the formation of hundreds to thousands of polyps and adenomas in the colon — the key characteristic of FAP.

Similar to Lynch syndrome, another hereditary colorectal cancer, FAP, is an autosomal dominant mutation which requires only one copy of the gene for the condition to manifest. The mutation can be passed from parent to child if it is found in reproductive cells such as the sperm or egg, making it a germline mutation.

With that being said, though, it is also possible for FAP to develop spontaneously instead of being inherited. About 30% of all FAP cases are a result of spontaneous rather than inherited mutations.

Adenomatous polyps

Regardless of whether the condition develops as a result of an inherited mutation or a spontaneous one, FAP is detected by the numerous polyps and adenomas that form in the colon, sometimes as early as one’s preteens. Without treatment, the polyps continue to proliferate throughout the colon and can become malignant even before the patient turns 40.

An alternative form of FAP, known as attenuated FAP (AFAP), is much harder to diagnose. Compared to classic FAP, the number of polyps formed in AFAP are much less, and are typically concentrated in the proximal colon. Compared to classic FAP, the age of colorectal cancer onset is also much later at 55 years.

Extracolonic cancers

Individuals diagnosed with FAP are also at risk of developing extracolonic cancers. This includes desmoid tumors, which are tumors that form on solid connective tissue. These tumors are often benign but can grow to be very large and are locally invasive.

Adenomas also develop in the stomach and small intestine — approximately 90% of FAP patients will experience this. However, in most cases, the adenomas are unlikely to develop into malignant adenocarcinomas.

In rarer cases, the FAP patient may develop hepatoblastoma or thyroid cancer.

The only way to ascertain if an individual has FAP is through genetic testing for mutations in the APC gene. Once an individual is identified, immediate family members are also advised to go for genetic testing.

While overcoming the initial distress that you or your family may have FAP is difficult, finding out earlier in life presents a better prognosis and a chance to begin managing the condition and lowering the risk of it developing into colorectal cancer.

Untreated FAP patients have a shorter life expectancy, and regular colonoscopy and screening is recommended for individuals who have been identified with the disease. This can begin as early as 10 to 12 years of age, and polypectomy can be done during the screening colonoscopy to remove any polyps located.

When the polyp load grows to a point where it can no longer be controlled with endoscopic removal, a colectomy is recommended to remove the colon, and possibly the rectum. The colon can be completely removed, but in cases where a subtotal colectomy is done, constant surveillance to investigate the risk of developing rectal cancer should be conducted. An ostomy, in which the surgeon creates a hole and stoma bag is applied to the skin, also required after surgery.

Other non-surgical treatments have limited effectiveness — drugs such as Sulindac can reduce the adenoma load by 50%, but cannot prevent a recurrence once the drug is discontinued.

Living with FAP is not easy, and the definitive treatment options are extensive and life-changing, but if there is a chance to eliminate the risk of developing colorectal cancer, the opportunity shouldn’t be disregarded. In the case of FAP, it is indeed better late than never.