Familial adenomatous polyposis (FAP)
FAP is an autosomal dominant disorder due to heritable germline mutations of the APC gene and causes the development of large numbers of colorectal adenomas at a young age. Classical FAP is defined by the presence of > 100 adenomas and young age of onset of polyposis; often thousands of adenomas are present. It is associated with a lifetime risk of CRC approaching 100% but accounts for ≤ 1% of all CRC cases. Common extra-colonic manifestations include gastric and duodenal polyps, desmoid tumours, osteomas and multiple lesions known as congenital hypertrophy of the retinal pigment epithelium (pigmented ocular lesions). Up to 30% of cases occur without a family history of FAP and represent either de novo germline mutations or mosaicism.
Attenuated FAP (AFAP) is also due to autosomal dominant mutations in the APC gene but there are fewer adenomas and a later onset of disease. The diagnosis should be considered in patients with a cumulative count of ≥ 10 adenomas before age 30 years or 20–99 adenomas at any age. In AFAP, adenomas may be predominantly in the proximal colon and there is often marked phenotypic variability within a family.
People with FAP also have an increased risk of extra-colonic malignancy, including malignancies of the upper gastrointestinal tract (most commonly duodenum), brain, thyroid and liver (hepatoblastoma). There is also an increased risk of desmoid tumours.
No systematic reviews on this topic were undertaken in the development of this section. The guidance on FAP is based on recent international guidelines. See Guidelines Development for more information.
Genetic testing[edit source]
Referral to a genetics service for germline genetic testing for mutations in APC is indicated for persons with a cumulative count of ≥ 10 colorectal adenomas before 30 years of age or ≥ 20 colorectal adenomas at any age. It is also indicated when a known pathogenic APC mutation is identified in a relative.
Over 70% of patients with a classical FAP phenotype have an APC mutation identified. Approximately 25% of patients with an attenuated FAP phenotype have an APC mutation identified. Finding a pathogenic mutation confirms the diagnosis and allows relatives to be tested with a very high degree of accuracy. Absence of a mutation in the proband does not definitively rule out the diagnosis though it does in the context of predictive testing of relatives where there is a known family specific mutation.
Surveillance should commence from age 10 to 15 years or earlier if there are gastrointestinal symptoms (Robays and Poppe, 2014). In families with classical FAP, flexible sigmoidoscopy is adequate since adenomas occur simultaneously throughout the colorectum (Syngal et al., 2015; Stoffel et al., 2015; Robays and Poppe, 2014). Once an adenoma is identified, annual colonoscopy should be performed until colectomy is undertaken. In AFAP, surveillance should be by colonoscopy since the first adenomas may only be present in the proximal colon but surveillance can be delayed until 18 years of age (Syngal et al., 2015; Cancer Institute NSW 2016; Robays and Poppe, 2014).
Surgical management[edit source]
In classical FAP, colectomy is required to prevent colorectal cancer and is usually performed between the ages of 15 and 25, once adenomas have been observed. The exact timing of surgery and the choice between a total colectomy with an ileorectal anastomosis, or a proctocolectomy with an ileal pouch-anal anastomosis (IPAA), depends on many factors including severity of polyposis in the rectum, risk of desmoid tumours and the desire to preserve fecundity and urinary, sexual and bowel function.
There is no evidence that risk reducing medication such as non-steroidal anti-inflammatory drugs (NSAIDs) prevent colorectal cancer in FAP. However, NSAIDs are well documented to reduce adenoma numbers in FAP, and all CRCs in FAP arise from adenomas. Where surgery is inappropriate (e.g. presenting also with complex intra-abdominal desmoid disease or adenomas in pouches) an NSAID (e.g. sulindac) is recommended. Refer to the Primary Prevention Part 2: Chemopreventive candidate agents chapter.
- Cancer Institute NSW. eviQ Cancer Genetics Referral Guidelines for Colorectal Cancer or Polyposis Risk Assessment and Consideration of Genetic Testing. [homepage on the internet] Sydney; 2016 [cited 2016 Sep 6]. Available from: https://www.eviq.org.au/Category/tabid/65/categoryid/6/Default.aspx.
- Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 2015 Feb;110(2):223-62; quiz 263 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25645574.
- Stoffel EM, Mangu PB, Gruber SB, Hamilton SR, Kalady MF, Lau MW, et al 2015. Hereditary colorectal cancer syndromes: American Society of Clinical Oncology Clinical Practice Guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology Clinical Practice Guidelines. Journal of Clinical Oncology 2015;33: 209-17 Available from: http://jco.ascopubs.org/content/early/2014/12/01/JCO.2014.58.1322.full.pdf.
- Barrow P, Khan M, Lalloo F, Evans DG, Hill J. Systematic review of the impact of registration and screening on colorectal cancer incidence and mortality in familial adenomatous polyposis and Lynch syndrome. Br J Surg 2013 Dec;100(13):1719-31 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24227356.
- Robays J, Poppe B. Oncogenetic testing for Lynch syndrome and familial adenomatous polyposis. Brussels: Belgian Health Care Knowledge Centre (KCE); 2014.
- Balmaña J, Balaguer F, Cervantes A, Arnold D, ESMO Guidelines Working Group.. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines. Ann Oncol 2013 Oct;24 Suppl 6:vi73-80 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23813931.