Cancer Res Treat.
2026 Apr;58(2):563-572. 10.4143/crt.2025.109.
Discrepancy between Genetically Predicted and Observed Alcohol Intake and Its Impact on Gastric Cancer Susceptibility
- Affiliations
-
- 1Interdisciplinary Program of Bioinformatics, Seoul National University, Seoul, Korea
- 2Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- 3Institute of Health and Environment, Seoul National University, Seoul, Korea
- 4Department of Public Health Sciences, Seoul National University, Seoul, Korea
- 5Department of Mathematical Data Science, Hanyang University (ERICA), Ansan, Korea
- 6Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam, Korea
- 7Center for Gastric Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Korea
- 8Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea
- 9Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- 10RexSoft Inc., Seoul, Korea
- KMID: 2580631
- DOI: http://doi.org/10.4143/crt.2025.109
Abstract
- Purpose
We aimed to investigate how genetic predisposition to drinking and gastric cancer (GC) modifies the association between alcohol consumption and GC risk in the Korean population.
Materials and Methods
Polygenic risk scores for GC (PRS-GC) and alcohol consumption (PRS-Alcohol) were formulated using genome-wide association results from BioBank Japan. Validation was performed using Korean cohorts (SNUBH-GENIE cohort), incorporating 8,846 controls and 531 patients with GC. Subsequently, these PRSs were applied to an independent Korean cohort of 67,771 participants, including 313 patients with GC during the follow-up for 14 years (KoGES cohort).
Results
In KoGES cohort, the influence of alcohol consumption on GC risk was significantly altered by the PRS-GC and exhibited a synergistic interaction effect. PRS-Alcohol itself shows a negative correlation with GC risk. However, when actual alcohol consumption significantly exceeded genetically predicted levels, the risk of alcohol-related GC was notably increased (adjusted hazard ratio, 1.32; 95% confidence interval, 1.01 to 1.72). Heavy drinkers in the high–PRS-GC/low–PRS-Alcohol group had a 2.16 times higher risk of GC than non-to-light drinkers, which was prominent in males.
Conclusion
Korean drinkers with higher PRS-GC who consume alcohol more than genetically predicted levels are susceptible to GC. PRS-GC and PRS-Alcohol may be beneficial for assessing the impact of alcohol consumption on GC risk in Koreans.
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