ScholarWorks@성균관대학교

초록

Simple Summary Bladder cancer occurs more frequently in men, yet the sex-specific effects of hyperglycemia and smoking on bladder cancer risk remain poorly understood, despite their established roles as modifiable risk factors. In this large, nationwide cohort study of over nine million Korean adults, we investigated the sex-specific associations of prediabetes, diabetes, and smoking with the risk of developing bladder cancer. The results showed that women exhibited a linear increase in risk with worsening glycemic status, whereas men demonstrated an apparent threshold pattern. Moreover, the combination of hyperglycemia and smoking synergistically elevated bladder cancer risk in women, while the effect was additive in men. Notably, the typical male predominance in bladder cancer incidence was attenuated in the presence of these risk factors. These findings suggest that women may be more vulnerable to the carcinogenic effects of hyperglycemia on the bladder, particularly when combined with smoking. Although the overall incidence is lower in women, those with both hyperglycemia and smoking exposure face a disproportionately high risk, underscoring the need for targeted education and prevention efforts in this vulnerable group. Background: Sex differences in the effects of hyperglycemia and smoking on bladder cancer risk remain poorly understood, despite their known roles as modifiable risk factors. We investigated the sex-specific associations of prediabetes, diabetes, and smoking with bladder cancer risk. Methods: We analyzed data from 9,492,331 cancer-free adults (54.8% men) who underwent the 2009 Korean national health screening. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for bladder cancer incidence were calculated using Cox proportional hazards models. Results: Over a median follow-up of 8.3 years, 12,095 men and 2467 women were diagnosed with bladder cancer. The male-to-female incidence ratio was 4.1:1 among never-smokers with normoglycemia and 2.7:1 among ever-smokers with diabetes. In women, both prediabetes and diabetes were associated with elevated bladder cancer risk (aHRs, 95% CIs: 1.12, 1.02-1.24; and 1.27, 1.13-1.43). In men, only diabetes showed an increased risk (aHR: 1.22, 1.12-1.32). Combined diabetes and smoking increased the risk synergistically in women (aHR: 2.75, 1.95-3.87; synergy index = 2.38, p < 0.01), while the effect was additive in men (aHR: 1.82, 1.70-1.95). Conclusions: The typical male predominance in bladder cancer incidence appeared attenuated in the presence of hyperglycemia and smoking, suggesting that these risk factors may have a relatively greater impact on bladder cancer risk among women. These findings underscore the importance of targeted bladder cancer prevention strategies, with particular attention to women with hyperglycemia who smoke, given their disproportionately elevated risk.

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