Clinical, Dietary, Lifestyle and Genetic Factors Associated With Age at Onset of Esophageal Adenocarcinoma
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Esophageal adenocarcinoma (EAC) represents one of the most increasing malignancies in Western countries. The disease is multifactorial, involving modifiable risk factors and genetic susceptibility variants. These variants can be aggregated to a polygenic risk score (PRS) that reflects individual genetic risk. Investigation of the effects of lifestyle factors, PRS, and co-medication on EAC age at onset (AAO) is critical for shaping prevention strategies. METHODS: A detailed questionnaire was used to assess pre-diagnostic exposure to lifestyle factors and clinical information from a large German EAC cohort. Linear regression analysis was performed to identify factors associated with EAC AAO in 1742 EAC patients. PRS was available for 1190 patients. Subgroup analyses were conducted to estimate the effects of the analyzed factors on AAO according to age group (early vs. late onset), sex, and prior diagnosis of Barrett's esophagus (BE). RESULTS: Earlier AAO was significantly associated with gastroesophageal reflux (GER), smoking and a higher PRS, whereas later AAO was associated with physical activity and higher consumption of fish and fruits. Among co-medication, combined use of proton pump inhibitors (PPIs) and acetylsalicylic acid (ASA) showed the most significant effect on AAO, whereas the use of PPIs and ASA alone showed weaker effects. DISCUSSION: This study represents the largest questionnaire-based analysis to date investigating factors influencing EAC development. Our findings show that the combined use of PPIs and ASA, both cost-effective medications, is associated with delayed EAC onset. In addition, lifestyle and genetics contribute to EAC AAO.
DOI: 10.1002/ueg2.70236
Authors: Vera Koch, Ines Gockel, Julian Reingruber, Nicole Kreuser, Jessica Bigge, Marino Venerito, Hakan Alakus, Andrea May, Christian Gerges, René Thieme, Dominik Heider, Axel M. Hillmer, Alanna Ebigbo, Christiane J. Bruns, Hauke Lang, Helmut Messmann, Thomas Rösch, Thaddäus T. Wissniowski, Michaela Müller, Ulrike W. Denzer, Markus M. Nöthen, Michael Vieth, Aaron P. Thrift, Carlo Maj, Johannes Schumacher
Institutions: Philipps University of Marburg, University Hospital of Basel, University Hospital Leipzig, University Hospital Magdeburg, Otto-von-Guericke-Universität Magdeburg, University Hospital Cologne, Helios Klinikum Krefeld, University of Münster, University of Cologne, University Hospital Augsburg, St. Josef-Hospital, Ruhr University Bochum, University Medical Center of the Johannes Gutenberg University Mainz, University Medical Center Hamburg-Eppendorf, Klinikum Chemnitz, Universitätsklinikum Gießen und Marburg, University of Bonn, University Hospital Bonn, Friedrich-Alexander-Universität Erlangen-Nürnberg, Bayreuth Medical Center, Baylor College of Medicine, Dan L Duncan Comprehensive Cancer Center
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,930
OpenAlex ID: W7164347257