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.
背景：尽管高血糖和吸烟是已知的可改变风险因素，但其对膀胱癌风险影响的性别差异仍未明确。本研究探讨了糖尿病前期、糖尿病及吸烟与膀胱癌风险的性别特异性关联。 方法：我们分析了9,492,331名无癌症病史的成年人（男性占54.8%）在2009年韩国国民健康体检中的数据。采用Cox比例风险模型计算膀胱癌发病的校正风险比（aHR）及其95%置信区间（CI）。 结果：在中位随访8.3年期间，共有12,095名男性和2,467名女性被诊断为膀胱癌。在血糖正常且从不吸烟的人群中，男女发病率比为4.1:1；而在有吸烟史的糖尿病患者中，该比例降至2.7:1。女性中，糖尿病前期和糖尿病均与膀胱癌风险升高相关（aHR及95% CI分别为1.12, 1.02–1.24和1.27, 1.13–1.43）。男性中仅糖尿病显示风险增加（aHR: 1.22, 1.12–1.32）。糖尿病与吸烟在女性中产生协同效应（aHR: 2.75, 1.95–3.87；协同指数=2.38, p<0.01），而在男性中仅呈相加效应（aHR: 1.82, 1.70–1.95）。 结论：膀胱癌发病率典型的男性主导特征在高血糖和吸烟状态下呈现减弱趋势，提示这些风险因素对女性膀胱癌风险的影响可能相对更大。鉴于吸烟高血糖女性群体的风险异常升高，这些发现强调了针对性膀胱癌预防策略的重要性，需特别关注该高危人群。
肿瘤(癌症)患者之家