Genetic Risk Mapping and Insights into Esophageal Adenocarcinoma Development

Background: Esophageal adenocarcinoma (EAC) is a malignant tumor that has been increasing in incidence over the past few decades. Identifying the risk factors associated with EAC is crucial for prevention and early detection strategies. Methods: This study aimed to investigate the potential risk factors for EAC using a Mendelian randomization (MR) approach. We attained genetic variants associated with 52 exposure factors s from available large-scale genome-wide association studies. Results: Genetic predisposition to childhood body mass index, forced expiratory volume in 1-second, glomerular filtration rate, telomere length, alcohol consumption, anxiety or depression, smoking, coffee consumption, time spent watching television, basal metabolic rate, body fat percentage, body mass index, hip circumference, obesity class 1, obesity class 2, trunk fat percentage, waist circumference, waist-to-hip ratio, iron, Barrett's esophagus, and gastroesophageal reflux disease were associated with increased risk of EAC. In addition, we demonstrated that age at first birth, age at first sexual intercourse, age at menarche, years of schooling, type 1 diabetes, and fruit intake could suggestively decrease the odds of EAC. Conclusion: This study represents the inaugural MR investigation to present a comprehensive atlas of risk factors associated with EAC, which will aid in advancing the formulation of efficacious preventive and early detection approaches.