Shin Jong Won, Minh Nguyen Thien, Jee Sun Ha
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Department of Epidemiology and Health Promotion, Institute for Health Promotion, School of Public Health, Yonsei University, Seoul 03772, Republic of Korea.
Healthcare (Basel). 2025 Jun 2;13(11):1321. doi: 10.3390/healthcare13111321.
Bilirubin is a potent endogenous antioxidant that plays a key role in regulating oxidative stress and inflammation, both closely linked to lung carcinogenesis. This study reinterprets the ALBI (Albumin-Bilirubin) and PALBI (Platelet-Albumin-Bilirubin) indices as composite markers of antioxidant and inflammatory status and evaluates their associations with lung cancer risk by sex, including stratified analyses by major lifestyle factors such as smoking and alcohol use. This study utilized data from the Korean Cancer Prevention Study-II (KCPS-II) cohort, which included 133,630 participants. During a mean follow-up of 13.5 years, 721 incident lung cancer cases were identified. Serum bilirubin and the ALBI and PALBI indices were analyzed by sex, and quartile-based and trend analyses were conducted. Stratified analyses by smoking and alcohol status (never, former, current, ever) and intensity were performed to assess potential effect modification. Cox proportional hazards regression models were used to estimate HRs and 95% CIs. : A 1SD increase in total bilirubin and ALBI was inversely associated with lung cancer risk in men (HR: 0.83, 95% CI: 0.75-0.91; HR: 0.86, 95% CI: 0.79-0.94, respectively), whereas PALBI showed a positive association (HR: 1.17, 95% CI: 1.07-1.28). In contrast, in women, total bilirubin and ALBI showed positive associations (HR: 1.19, 95% CI: 1.00-1.40; HR: 1.19, 95% CI: 1.02-1.40, respectively), while PALBI was inversely associated (HR: 0.82, 95% CI: 0.69-0.97). These associations were significant among men who were smokers (former, current, ever) and men who drank alcohol (current, ever), whereas in women, significance was observed only among never drinkers. Stronger interactions were observed in men who were heavy smokers and low-to-moderate drinkers. Bilirubin and the ALBI and PALBI indices exhibit sex-specific and contrasting associations with lung cancer risk, highlighting the need to consider sex-based physiological differences in cancer risk assessment.
胆红素是一种强大的内源性抗氧化剂，在调节氧化应激和炎症方面发挥着关键作用，而氧化应激和炎症都与肺癌发生密切相关。本研究将ALBI（白蛋白-胆红素）和PALBI（血小板-白蛋白-胆红素）指数重新诠释为抗氧化和炎症状态的综合标志物，并按性别评估它们与肺癌风险的关联，包括按吸烟和饮酒等主要生活方式因素进行分层分析。本研究利用了韩国癌症预防研究-II（KCPS-II）队列的数据，该队列包括133,630名参与者。在平均13.5年的随访期间，确定了721例肺癌病例。按性别分析血清胆红素以及ALBI和PALBI指数，并进行基于四分位数的分析和趋势分析。按吸烟和饮酒状态（从不、曾经、现在、曾经有过）及强度进行分层分析，以评估潜在的效应修正。使用Cox比例风险回归模型来估计风险比（HR）和95%置信区间（CI）。总胆红素和ALBI每增加1个标准差与男性肺癌风险呈负相关（HR：0.83，95%CI：0.75 - 0.91；HR：0.86，95%CI：0.79 - 0.94），而PALBI呈正相关（HR：1.17，95%CI：1.07 - 1.28）。相比之下，在女性中，总胆红素和ALBI呈正相关（HR：1.19，95%CI：1.00 - 1.40；HR：1.19，95%CI：1.02 - 1.40），而PALBI呈负相关（HR：0.82，95%CI：0.69 - 0.97）。这些关联在吸烟男性（曾经、现在、曾经有过）和饮酒男性（现在、曾经有过）中显著，而在女性中，仅在从不饮酒者中观察到显著关联。在重度吸烟且低度至中度饮酒的男性中观察到更强的相互作用。胆红素以及ALBI和PALBI指数与肺癌风险呈现出性别特异性且相反的关联，凸显了在癌症风险评估中考虑基于性别的生理差异的必要性。
