背景:评估睡眠和肝功能生物标志物对肝癌的单独和联合影响。
方法:分析了在英国生物库基线时没有癌症的356,894名参与者的数据。使用五种睡眠特征(睡眠持续时间,时间型,失眠,打鼾,和白天过度嗜睡)并分为健康或不健康的睡眠。测量循环肝功能生物标志物。使用Cox比例风险模型来研究睡眠和肝功能生物标志物与肝癌发病率的独立和联合关联。
结果:中位随访时间13.1年后,记录了394例肝癌事件。肝癌的多变量校正风险比(HR)为1.46(95%置信区间:1.15-1.85)健康睡眠),和1.17(1.15-1.20),1.20(1.18-1.22),1.69(1.47-1.93),1.06(1.06-1.07),1.08(1.07-1.09),1.81(1.37-2.39),或0.29(0.18-0.46)与丙氨酸转氨酶(ALT)每增加10个单位相关,天冬氨酸转氨酶(AST),总胆红素(TBIL),γ-谷氨酰转移酶(GGT),碱性磷酸酶(ALP),总蛋白(TP),或白蛋白(ALB),分别。睡眠不健康和高(≥中位数)ALT的个体,AST,TBIL,GGT,ALP,或TP或低(<中位数)ALB水平的最高HR为3.65(2.43-5.48),4.03(2.69-6.03),1.97(1.40-2.77),4.69(2.98-7.37),2.51(1.75-3.59),2.09(1.51-2.89),或2.22(1.55-3.17)肝癌,分别。由于0.80(0.19-1.41)的相互作用,观察到不健康睡眠与高TP水平对肝癌的显着累加相互作用,具有相对超额风险。
结论:不健康的睡眠与肝癌风险增加有关,尤其是在ALB水平较低或ALT水平较高的参与者中,AST,TBIL,GGT,ALP,特别是TP。
BACKGROUND: To assess the largely undetermined separate and joint effects of sleep and liver function biomarkers on liver cancer.
METHODS: Data of 356,894 participants without cancer at baseline in the UK Biobank were analyzed. Sleep score was evaluated using five sleep traits (sleep duration, chronotype, insomnia, snoring, and excessive daytime sleepiness) and dichotomized into healthy or unhealthy sleep. Circulating liver function biomarkers were measured. Cox proportional hazard model was performed to investigate the independent and joint associations of sleep and liver function biomarkers with liver cancer incidence.
RESULTS: After a median follow-up time of 13.1 years, 394 cases of incident liver cancer were documented. The multivariable-adjusted hazard ratio (HR) for liver cancer was 1.46 (95% confidence interval: 1.15-1.85) associated with unhealthy sleep (vs. healthy sleep), and was 1.17 (1.15-1.20), 1.20 (1.18-1.22), 1.69 (1.47-1.93), 1.06 (1.06-1.07), 1.08 (1.07-1.09), 1.81 (1.37-2.39), or 0.29 (0.18-0.46) associated with each 10-unit increase in alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), or albumin (ALB), respectively. Individuals with unhealthy sleep and high (≥ median) ALT, AST, TBIL, GGT, ALP, or TP or low (< median) ALB level had the highest HR of 3.65 (2.43-5.48), 4.03 (2.69-6.03), 1.97 (1.40-2.77), 4.69 (2.98-7.37), 2.51 (1.75-3.59), 2.09 (1.51-2.89), or 2.22 (1.55-3.17) for liver cancer, respectively. Significant additive interaction of unhealthy sleep with high TP level on liver cancer was observed with relative excess risk due to an interaction of 0.80 (0.19-1.41).
CONCLUSIONS: Unhealthy sleep was associated with an increased risk of liver cancer, especially in participants with lower ALB levels or higher levels of ALT, AST, TBIL, GGT, ALP, or particularly TP.