Body mass index change trajectories and gastric cancer risk: Effect modification by sex, age, smoking, and menopausal status in Korean adults aged ≥40 years

This study examined the association between body mass index (BMI) and gastric cancer risk and specifically evaluated effect modification by sex, age, smoking, and menopausal status. A nationwide cohort of cancer-free Korean adults aged ≥40 years who underwent standardized health examinations in 2009 and 2013 was followed through 2017. BMI was classified into five categories (<18.5, 18.5-22.9, 23-24.9, 25-29.9, and ≥30 kg/m2), and BMI changes were grouped into 25 trajectories. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for gastric cancer were estimated using Cox proportional hazards models, with formal interaction testing for key modifiers. Among 2,800,588 participants (52.8% women), 14,662 incident gastric cancers were identified. Persistent obesity I was consistently associated with an increased gastric cancer risk in total population and most subgroups, including both men and women, both smoking groups, postmenopausal women, and individuals aged < 60 years. In contrast, modest BMI gain from normal to overweight was associated with a reduced risk of gastric cancer in men (aHR 0.90; 95% CI: 0.82-1.00), smokers (aHR 0.88; 95% CI 0.79-0.99), and individuals aged < 60 years (aHR 0.87; 95% CI 0.77-0.98). Persistent obesity II was associated with an increased risk in never smokers. Both underweight and persistent obesity I were associated with an increased risk in those aged < 60 years. BMI change from obesity I to overweight reduced gastric cancer risk (aHR 0.54; 95% CI 0.32-0.92) in premenopausal women, whereas persistent obesity I and BMI gain (underweight to normal) were associated with increased gastric cancer risk in postmenopausal women; however, these findings were exploratory. In conclusion, BMI changes are associated with gastric cancer risk, with clear effect modification by sex, age, and smoking status.