P0434 - Multi-Center, International Study of Colonoscopy Findings in Patients With CDH1 and CTNNA1 Germline Pathogenic Variants

Award: Presidential Poster Award

Arjun Chatterjee, MD¹, Robert Hüneburg, MD², Qijun Yang, MS³, Shannon Morrison, MS¹, Anna Bettzüge, MD², Tim Marwitz, MD², Stefan Aretz, MD², Isabel Spier, MD², Tim Ripperger, MD⁴, Silke Redler, MD⁵, Mykyta Kachanov, MD⁶, Alexander Volk, MD⁶, Deepak Vangala, MD⁷, Severin Daum, MD⁸, Elke Holinski-Feder, MD⁹, Verena Steinke-Lange, MD⁹, Kathrin Bahlke, MD¹⁰, Christian Strassburg, MD¹¹, Lady Katherine Mejia-Perez, MD¹², Margaret O'Malley, ¹, Lisa LaGuardia, RN¹², David Liska, MD¹, Carole Macaron, MD¹², Joshua Sommovilla, MD¹, Jacob Nattermann, MD², Carol A.. Burke, MD, FACG^12
1Cleveland Clinic Foundation, Cleveland, OH; ²University Hospital, Bonn, Nordrhein-Westfalen, Germany; ³Cleveland Clinic, Cleveland, OH; ⁴Hannover Medical School, Hannover, Niedersachsen, Germany; ⁵University Hospital Düsseldorf, Düsseldorf, Nordrhein-Westfalen, Germany; ⁶University Hospital, Hamburg, Hamburg, Germany; ⁷Ruhr-University Bochum, Bochum, Nordrhein-Westfalen, Germany; ⁸Klinikum der Universität München, Munich, Mecklenburg-Vorpommern, Germany; ⁹Klinikum der Universität München, Munich, Bayern, Germany; ¹⁰University Hospital, Münster, Nordrhein-Westfalen, Germany; ¹¹University Hospital, Bonn, Niedersachsen, Germany; ¹²Digestive Disease Institute, Cleveland Clinic, Cleveland, OH

Introduction: Germline pathogenic variants (PV) in CDH1 and CTNNA1 are hereditary causes of diffuse gastric cancer (HDGC) and CDH1 is associated with lobular breast cancer. Previous studies report disparate findings on colorectal neoplasia risk in CDH1 PV carriers yet data are scarce. We investigated colorectal neoplasia in an international cohort of patients with CDH1 and CTNNA1 PVs undergoing colonoscopy.

Methods: In this IRB approved study, adults carrying a PV in CDH1/CTNNA1 with ≥1 colonoscopy between 01/01/2004 – 12/31/2023 were included. Patients were sourced from the David G. Jagelman Inherited Colorectal Cancer Registries at Cleveland Clinic and the German Consortium for Familial Intestinal Cancer.

Results: The study included 109 patients: 103 (94.5%) with a CDH1 PV and 6 (5.5%) with a CTNNA1 PV. The majority were female (66.1%) and white (93.3%). Gastric and breast cancer were reported in 47% and 40% of patients, respectively. (Table 1). In the 6 CTNNA1 PV carriers, age of at initial colonoscopy was 54.2 years; normal in 5 and 1 patient had a non-advanced adenoma, no CRC were detected. In CDH1, 88% of colonoscopies were screening exams at median starting age of 47 years. ADR and SSLDR were 29.4% and 8.8% in the German cohort and 48.6% and 11.4% in the Cleveland cohort, respectively. (Table 2). CRC was detected in 3 patients (2.9%) at ages 29 (Stage 3), 69 (Stage IV), and 49 (Stage 1). ADR in CDH1 varied by age: 13.6% (< 45 years), 52.4% (45-49 years), and 52.6% (≥50 years; p < 0.001). (Table 3) Advanced adenomas (2.9%) and advanced SSLs (3.9%) were detected only in the German cohort and were found in individuals younger than age 45.

Discussion: This international study examining colonoscopy outcomes was comprised largely by CDH1 PV carriers. In that predominantly female and young cohort, ADR in both countries was higher than the U.S. [28.4% in 45-49 years]¹ and German average ADR [31.3% in men and 20.1% in women >55 years]². Additionally, CRC was detected in 2.9% at median age of 49. These finding suggest an increased risk of CRC in CDH1 PV, advocating for colonoscopies starting at age 40, with no increased risk in CTNNA1 PV carriers.

¹doi:10.1053/j.gastro.2021.09.028; ²doi:10.1053/j.gastro.2015.04.012


Disclosures:


Arjun Chatterjee, MD¹, Robert Hüneburg, MD², Qijun Yang, MS³, Shannon Morrison, MS¹, Anna Bettzüge, MD², Tim Marwitz, MD², Stefan Aretz, MD², Isabel Spier, MD², Tim Ripperger, MD⁴, Silke Redler, MD⁵, Mykyta Kachanov, MD⁶, Alexander Volk, MD⁶, Deepak Vangala, MD⁷, Severin Daum, MD⁸, Elke Holinski-Feder, MD⁹, Verena Steinke-Lange, MD⁹, Kathrin Bahlke, MD¹⁰, Christian Strassburg, MD¹¹, Lady Katherine Mejia-Perez, MD¹², Margaret O'Malley, ¹, Lisa LaGuardia, RN¹², David Liska, MD¹, Carole Macaron, MD¹², Joshua Sommovilla, MD¹, Jacob Nattermann, MD², Carol A.. Burke, MD, FACG¹². P0434 - Multi-Center, International Study of Colonoscopy Findings in Patients With CDH1 and CTNNA1 Germline Pathogenic Variants, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.