Family History, Surgery, and APC Mutation Are Risk Factors for Desmoid Tumors in Familial Adenomatous Polyposis: An International Cohort Study

Abstract

A positive family history for desmoid tumors, abdominal surgery, and APC mutation site are significant risk factors for development of desmoid tumors. The results may have implications for determining the optimal management of FAP patients and guide future studies.

Desmoid Tumors in Familial Adenomatous Polyposis

“…The incidence of DTs in FAp is 800-to 1,000-fold higher than in the general population (22): DTs occur in between 10% (23) and 15% of patients with FAp (6).…”

“…in particular, individuals with mutations of the APC gene beyond codon 1,444 are at a 12-fold higher risk of developing DTs (29); in some reports, APC mutations are associated with a 65% risk of developing mesenteric DTs (30). A peculiar risk factor for the development of DTs is surgical trauma: most DTs develop within 5 years after surgery (22,23), in particular 68-83% DTs after abdominal operations, mostly within 24 months (11). Any possibly protective role of minimally invasive surgery is still to be determined (11).…”

“…Evidence for medical therapy in DTs has been proposed even if with few limited results, mainly related to the low numbers of patients and the pleomorphism in presentation and evolution of DTs (22,54,66). Non-steroidal antiinflammatory drug (NsAiD) therapy, in particular with sulindac, has been suggested for DTs in FAp (6,(70)(71)(72), with reports evidencing stable disease or regression in up to 29% of cases (3).…”

“…Traditional chemotherapy is a proven therapy for DTs, where different protocols have been proposed: doxorubicin and dacarbazine (81), methotrexate and vinblastine (82), doxorubicin and carboplatin or dacarbazine or ifosfamide (22).…”

Nationwide Trends in the Current Management of Desmoid (Aggressive) Fibromatosis

“…In the remaining 15% of desmoid fibromatosis cases, tumour development is thought to be driven by mutations in the gene that encodes for APC. These mutations result in an abnormally short APC protein that is unable to bind to B-catenin, resulting indirectly in B-catenin accumulation [3,4]. It is this pathway that is associated with the intra-abdominal fibromatoses associated with Gardner's syndrome.…”