Cause of FAP
FAP is caused by a germline mutation of the adenomatous polyposis coli (APC) gene. This provides instructions for making the APC protein, which plays a critical role in several cellular processes that determine whether a cell will develop into a tumour.
The inheritance of FAP is autosomal dominant so all individuals carrying the gene mutation have a 50% chance of passing it on to the next generation. Approximately 70% of subjects have inherited the mutated gene.
Signs and symptoms of FAP
APC gene mutation carriers have regular checks for polyps from a young age. But, as FAP can happen with no family history, the first sign of it may be bowel symptoms. However, patients often present with no symptoms at all.
Symptoms of FAP include:
- Blood or mucous in the stools
- Changes in bowel habits
- Abdominal pain
- Weight loss for no obvious reason
Treatment
Patients are managed through regular endoscopic surveillance. Polyps are controlled by polypectomy or ablation (the latter for small rectal polyps found in patients who have already undergone surgery). Where this provides inadequate control, the colon and, possibly the rectum, are removed surgically.
Surgical options include:
- Colectomy with ileo-rectal anastomosis
- Proctocolectomy with ileal pouch anal anastomosis
- Proctocolectomy with permanent ileostomy
Rationale for chemoprevention and chemoregression
Each polyp has the potential to develop into cancer. The risk of cancer increases with the number of polyps so, preventing their development, or promoting regression, should reduce the risk of colorectal cancer.
Several critical aspects of the clinical care of patients with FAP are driven, primarily, by the number, size and morphology of the polyps.
These include:
- Timing and type of surgery
- Frequency of surveillance examinations
- Number of polypectomies.
References
- Hull MA, et al., (2004) Mol Cancer Ther; 3:1031-1039. Prostaglandin EP receptors: Targets for treatment and prevention of colorectal cancer
- Half E, et al., (2009) Orphanet J Rare Dis; 4:22. Review. Familial adenomatous polyposis
- West NJ, et al., (2010) Gut; 59: 918-925. Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis
