Familial Adenomatous Polyposis 1

1. Disease Summary:

Familial Adenomatous Polyposis (FAP) is a hereditary condition characterized by the development of numerous adenomatous polyps in the colon and rectum, typically beginning in adolescence or early adulthood. If left untreated, these polyps have a nearly 100% risk of progressing to colorectal cancer by the age of 50. FAP is caused by mutations in the adenomatous polyposis coli (APC) gene, which is a tumor suppressor gene. In addition to colorectal manifestations, FAP can lead to various extracolonic manifestations, including desmoid tumors, osteomas, and dental abnormalities. The condition is inherited in an autosomal dominant manner, meaning that an affected individual has a 50% chance of passing the mutation to their offspring.

2. Global Prevalence and Disease Burden:

FAP has an estimated prevalence of approximately 1 in 8,300 to 1 in 37,600 individuals in the general population, with variations based on geographic and ethnic factors. The disease burden is significant, as individuals with FAP face not only the risk of colorectal cancer but also the psychological and social impacts of living with a hereditary cancer syndrome. The economic burden includes costs associated with surveillance, prophylactic surgeries, and management of complications, as well as indirect costs related to lost productivity and the need for ongoing medical care.

3. Unmet Medical Need:

Despite the availability of prophylactic surgical options, there are several unmet medical needs for individuals with FAP:

Psychological Support: Approximately 20% of individuals with FAP experience moderate to severe psychological distress related to their condition, with many reporting unmet needs for psychosocial support (Douma et al., 2010, PMID: 19382100). The psychological burden is compounded by the hereditary nature of the disease, leading to anxiety about cancer risk and the implications for family members.
Effective Chemoprevention: Current chemopreventive strategies, such as the use of NSAIDs (e.g., sulindac and celecoxib), have shown limited effectiveness in completely suppressing adenoma growth. There is a need for more effective chemopreventive agents that can delay or prevent the onset of polyps and associated cancers (Lynch, 2016, PMID: 27083160).
Comprehensive Care Models: Many patients report a lack of coordinated care and insufficient knowledge among healthcare providers regarding FAP. This can lead to gaps in surveillance and management, increasing the risk of complications (Friedl & Aretz, 2005, PMID: 20223039).
Long-term Surveillance: Patients require lifelong surveillance for colorectal and extracolonic cancers, but the current guidelines may not adequately address the individual needs of patients, particularly regarding the timing and frequency of screenings (Church, 2009, PMID: 19793567).
Education and Awareness: There is a significant need for improved education and awareness about FAP among both patients and healthcare providers to ensure timely diagnosis and management.

4. Current Treatment Options:

The primary treatment for FAP is prophylactic surgery, which includes:

Total Colectomy: This is the standard surgical intervention to prevent colorectal cancer. It involves the removal of the entire colon and is often accompanied by the creation of an ileal pouch-anal anastomosis (IPAA) or ileorectal anastomosis (IRA). While these surgeries significantly reduce cancer risk, they do not eliminate the risk of developing cancer in the remaining rectal tissue or other organs (Church, 2009, PMID: 19793567).
Chemoprevention: Nonsteroidal anti-inflammatory drugs (NSAIDs) like sulindac and selective COX-2 inhibitors like celecoxib have been used to reduce polyp burden. However, their effectiveness is variable, and they are not a substitute for surgical intervention (Lynch, 2016, PMID: 27083160).
Surveillance: Regular endoscopic surveillance is essential for detecting new polyps and managing any complications. However, the frequency and methods of surveillance can vary, leading to potential gaps in care (Douma et al., 2010, PMID: 19382100).

5. Current Clinical Trials:

Several clinical trials are currently investigating new treatment options for FAP, including:

Metformin: A recent study has shown that metformin may be effective in reducing polyp burden in FAP patients by modulating intestinal flora (Zhou et al., 2024, PMID: 38403687).
Combination Therapies: Ongoing trials are exploring the use of combination therapies that include chemopreventive agents and novel drugs targeting specific pathways involved in polyp formation.
Psychosocial Interventions: Trials focusing on the psychological support needs of FAP patients are also being conducted to assess the effectiveness of counseling and support programs.

6. Additional Context:

The management of FAP requires a multidisciplinary approach involving genetic counseling, surgical intervention, and ongoing surveillance. The psychological and social implications of living with FAP are significant, and addressing these needs is crucial for improving the overall quality of life for affected individuals. Enhanced education and awareness among healthcare providers and patients can lead to better outcomes and more effective management of this hereditary condition.