K. D. Feagins1, S. O’Brien1, T. Kalbfleisch2, H. C. Polk1, S. Galandiuk1 1University Of Louisville, Price Institute Of Surgical Research, Louisville, KY, USA 2University Of Kentucky, Gluck Equine Research Center, Lexington, KY, USA
Introduction: Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome defined by APC gene mutations with numerous colonic adenomas developing early in life. Cancer risk is nearly 100% for FAP patients without intervention. The APC gene on chromosome 5q22 encodes a protein regulating Wnt signaling, ultimately functioning as a tumor suppressor.
Conversely, Crohn’s disease (CD) an inflammatory bowel disease with mechanisms not completely defined, is characterized by chronic inflammation and/or fibrostenotic strictures within the gastrointestinal tract. CD etiology is multifactorial; many genetic loci have been associated with CD and some (IBD5) are also on chromosome 5q.
We have identified a unique group of individuals with both disorders and hypothesize that there is an association between FAP and CD given the geographic proximity of IBD5 and APC on Chromosome 5.
We aim to:
1)assess the prevalence of previously identified cases of coexisting FAP and CD in the literature.
2)perform next generation sequencing (NGS) in dually diagnosed patients.
Methods: 1)We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews (PRISMA). The PubMed, Embase, Ovid and Web of Science databases, dates from January 1950 to July 2020 were searched. A Google Scholar search was also performed. A search of grey literature was performed including Digestive Disease Week archives from 1974-2020. Relevant datapoints were extracted for descriptive analysis.
2)Whole blood was obtained from 8 patients with both FAP & CD after obtaining informed consent. NGS was performed, reads produced were mapped to the human reference genome build 38 at an average depth of coverage of 20X with paired end 150 base read length.
Results: Initial search yielded 1,214 articles. Inclusion criteria included full-text articles presenting coexisting/sequential cases of both FAP and CD. After titles and abstract screening, 1,120 articles were excluded with 94 selected for full text assessment; 12 were selected for systematic review, each describing patients with FAP and CD.
In our institution, we identified 4 cases of FAP associated with CD. NGS analysis showed each of these patients who are phenotypically similar to share the same genetic mutation; an 11 KB deletion in promoter 1B of the APC gene.
Conclusion: A systematic literature review yielded an additional 8 cases phenotypically similar to ours. Some articles include a comprehensive description of genetic data with little phenotypic detail. Conversely, other articles are clinical reports, without a genetic analysis. We have confirmed an 11KB APC promoter deletion in individuals with coexisting FAP and Crohn’s disease. Due to the infrequency of this mutation, and the co-occurrence of these conditions, further study may provide additional information regarding the etiology of Crohn’s disease in these patients.