Year: 2025
Type: article
Study design: Observational Study
Abstract: Germline (likely-)pathogenic variants (PV) in CDH1 predispose carriers to hereditary diffuse gastric cancer and lobular breast cancer. Previous studies from the United States suggest CDH1 variant carriers have an increased risk for adenomas or sessile serrated lesions (SSL), yet data linking CDH1 PVs and colorectal neoplasia are scarce. We aimed to investigate colonoscopy findings in CDH1 PVs. Adults carrying a PV/LPV in CDH1 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. 103 CDH1 PV carriers were included. Most were female (66%) and white (93.1%). The median age at first colonoscopy was 47 years. The adenoma detection rate (ADR) was 29.4% (95% CI:19.9-41.1%) in the German cohort and 48.6% (95% CI: 33.0-64.4%) in the Cleveland cohort (p = 0.055) and significantly correlated with age (< 45 years, 13.6% (95% CI: 6.40-26.7%); 45-49 years, 52.4% (95% CI: 32.4-71.7%); ≥50 years, 52.6% (95% CI: 37.3-67.5%); p < 0.001). The ADR in Cleveland was higher than the U.S. average ADR but the difference was not statistically significant (48.6% vs. 35.6%, p = 0.08), and the ADR in the German cohort (29.4%) was similar to the national German average risk screening cohort (31.3% in men, p = 0.84; 20.1% in women, p = 0.08). In our screening cohort with CDH1 PV carriers, we demonstrated an ADR of 13.5% in individuals under 45 years, similar to the ADR in patients aged 25-40 years with a family history of CRC. Overall, SSL detection rate was 9.7%. Colorectal cancer was diagnosed in 3 patients (3.2%), 2/3 with an early age of onset before the age of 50 years. This first international study provides preliminary evidence of a higher ADR in U.S. CDH1 PV carriers compared to the general population, with a high number of adenomas detected before the age of 50. This may indicate an increased CRC risk that should be explored in larger studies.
Source: Familial Cancer
Authors: Arjun Chatterjee, Robert Hüneburg, Qijun Yang, Shannon Morrison, Anna Bettzüge, Tim Marwitz, Stefan Aretz, Isabel Spier, Tim Ripperger, Silke Redler, Mykyta Kachanov, Alexander E. Volk, Deepak B. Vangala, Severin Daum, Elke Holinski-Feder, Verena Steinke-Lange, Kathrin Bahlke, Christian P. Strassburg, Lady Katherine MejiaPerez, Margaret M. O’Malley, Lisa LaGuardia, David Liska, Carole Macaron, Joshua Sommovilla, Carol A. Burke, Jacob Nattermann
Institutions: Cleveland Clinic, University of Bonn, University Hospital Bonn, ERN GENTURIS, Medizinische Hochschule Hannover, Düsseldorf University Hospital, Heinrich Heine University Düsseldorf, University Medical Center Hamburg-Eppendorf, Ruhr University Bochum, Charité - Universitätsmedizin Berlin, LMU Klinikum, Medical Genetics Center, Ludwig-Maximilians-Universität München, University Hospital Münster
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,990
OpenAlex ID: W4410099026