Familial adenomatous polyposis: the practical applications of clinical and molecular screening

Abstract

Familial adenomatous polyposis (FAP) is an autosomal dominant condition mostly due to a mutation of the APC gene on the chromosome 5q. Carriers have an almost 100% chance of developing colorectal cancer after having multiple (typically 100s to 1000s) of adenomatous polyps. It is usually readily identified through this phenotype of multiple adenomas. Correlations between the location of the family-specific mutation on the APC gene and clinical manifestations of the disease are of some assistance in clinical management, though there is heterogeneity in clinical course even between family members with the same mutation. FAP is important to recognize, as there are disease-specific management implications with respect to offering mutational analysis of the APC (and perhaps other) genes for predictive testing of other family members, endoscopic diagnostic procedures, surveillance planning, and surgical management. Extra-colonic manifestations, including duodenal polyposis, desmoid disease and other tumours, can dominate clinical care after colectomy. The inheritable and lethal nature of the disease, together with the availability of effective treatment strategies, makes a sensitive clinical and psychosocial approach important to maximize compliance and good outcomes for all members of affected families.

Mainstreaming genetic testing of cancer predisposition genes

“…Prevention usually involves surgical removal of the at-risk tissue and is necessarily reserved for nonessential organs in individuals at very high-risk, such as the stomach in CDH1 mutation carriers, the thyroid in RET mutation carriers and the breast and ovaries in BRCA1 mutation carriers. [14][15][16] Chemoprevention is an attractive strategy, but to date there have been few applications. A notable exception is individuals with increased risk of colorectal cancer in whom the cancer risk is signifi cantly reduced by daily aspirin.…”

Molecular approach to genetic and epigenetic pathogenesis of early-onset colorectal cancer

“…Moreover, the depletion of APC can lead to abnormal chromosome segregation and aberrant mitosis [65,66] . FAP occurs when there are mutations between codons 168-1580 and with severe disease between codons 1250-1464 of APC gene [67,68] . The majority of APC mutations are either frameshift or nonsense mutations resulting in a truncated protein [69] .…”

Preferences for genetic testing for colorectal cancer within a population-based screening program: a discrete choice experiment

“…However, this is the most aggressive and severe genetic variant of CRC for which active screening is of utmost importance. 38,39 Fortunately, most FAP patients are aware of their predisposition from a young age due to a family history resulting in an acceptable surveillance compliance. 40 However, when clinicians suspect individuals may have FAP without a clear family history, they are advised to (continue to) stress the importance of active screening once genetic predisposition is confirmed.…”