Desmoid tumors complicating Familial Adenomatous Polyposis: a meta-analysis mutation spectrum of affected individuals

Voytek Slowik, Thomas Attard, Hongying Dai, Raj Shah, Seth Septer

Desmoid tumors are a group of benign, invasive, solid tumors that are relatively rare in the general population, but can occur in up to 21 % of patients with Familial Adenomatous Polyposis (FAP). They can be difficult to treat and have high rates of recurrence even after resection. Our goal with this study was to identify the genetic mutations that put certain patients with FAP at high risk for desmoid tumors and could be future targets for research. We performed a search in Pubmed, Ovid Medline and Embase to identify subjects with desmoid tumors and FAP. As a reference group for APC mutations in the unselected FAP population, we used the UMD-APC database referenced in the Orphanet portal which includes APC mutation data on 2040 individuals with FAP. Mutations were able to be broken down into 7 regions based on previously published data. Mutations in the APC gene from codons 1310 to 2011 were the most common region encompassing 48 % of published desmoid cases and 40 % of the reference population. It had a slightly elevated odds ratio of 1.4 that was statistically significant along with codon region 543-713 that had an odds ratio of 2.0. Using a combination of p-value and CI, the remaining 5 regions did not meet statistical significance as either the p >0.05 or the CI included 1.0. The most common point mutation found was codon 1309 (13.1 %), but it was also the most commonly found mutation in our reference population (12.9 %) and had an odds ratio of 1.0. There is an increased risk for desmoid tumors in individuals with APC mutations between codons 543-713 and 1310-2011 when compared to a reference population. These patients may benefit from further study to develop surveillance protocols that could improve outcomes.