Huang Changzhi, Lu Jiayi, Yang Jing, Wang Zhenling, Hang Dong, Fu Zan
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Front Mol Biosci. 2024 Apr 25;11:1209349. doi: 10.3389/fmolb.2024.1209349. eCollection 2024.
Cystatin C (CysC), beyond its biomarker role of renal function, has been implicated in various physical and pathological activities. However, the impact of serum CysC on cancer mortality in a general population remains unknown. We aimed to examine the associations of serum CysC concentrations with total mortality and mortality of 12 site-specific cancers.
We included 241,008 participants of the UK Biobank cohort with CysC measurements who had normal creatinine-based estimated glomerular filtration rates and were free of cancer and renal diseases at baseline (2006-2010). Death information was obtained from the National Health Service death records through 28 February 2021. Multivariable Cox proportional hazards models were used to compute hazard ratios (HR) per one standard deviation increase in log-transformed CysC concentrations and 95% confidence intervals (95% CI) for mortality.
Over a median follow-up of 12.1 (interquartile range, 11.3-12.8) years, 5,744 cancer deaths occurred. We observed a positive association between serum CysC concentrations and total cancer mortality (HR = 1.16, 95% CI: 1.12-1.20). Specifically, participants with higher serum CysC concentrations had increased mortality due to lung cancer (HR = 1.12, 95% CI: 1.05-1.20), blood cancer (HR = 1.29, 95% CI: 1.16-1.44), brain cancer (HR = 1.19, 95% CI: 1.04-1.36), esophageal cancer (HR = 1.20, 95% CI: 1.05-1.37), breast cancer (HR = 1.18, 95% CI: 1.03-1.36), and liver cancer (HR = 1.49, 95% CI: 1.31-1.69).
Our findings indicate that higher CysC concentrations are associated with increased mortality due to lung, blood, brain, esophageal, breast, and liver cancers. Future studies are necessary to clarify underlying mechanisms.
胱抑素C（CysC）除了具有肾功能生物标志物的作用外，还参与了多种生理和病理活动。然而，血清CysC对普通人群癌症死亡率的影响尚不清楚。我们旨在研究血清CysC浓度与总死亡率以及12种特定部位癌症死亡率之间的关联。
我们纳入了英国生物银行队列中241,008名进行了CysC测量的参与者，这些参与者基于肌酐的估计肾小球滤过率正常，且在基线时（2006 - 2010年）没有癌症和肾脏疾病。通过2021年2月28日之前的英国国家医疗服务体系死亡记录获取死亡信息。使用多变量Cox比例风险模型计算对数转换后的CysC浓度每增加一个标准差时的风险比（HR）以及死亡率的95%置信区间（95%CI）。
在中位随访12.1年（四分位间距，11.3 - 12.8年）期间，发生了5744例癌症死亡。我们观察到血清CysC浓度与总癌症死亡率之间存在正相关（HR = 1.16，95%CI：1.12 - 1.20）。具体而言，血清CysC浓度较高的参与者因肺癌（HR = 1.12，95%CI：1.05 - 1.20）、血癌（HR = 1.29，95%CI：1.16 - 1.44）、脑癌（HR = 1.19，95%CI：1.04 - 1.36）、食管癌（HR = 1.20，95%CI：1.05 - 1.37）、乳腺癌（HR = 1.18，95%CI：1.03 - 1.36）和肝癌（HR = 1.49，95%CI：1.31 - 1.69）导致的死亡率增加。
我们的研究结果表明，较高的CysC浓度与肺癌、血癌、脑癌、食管癌、乳腺癌和肝癌导致的死亡率增加有关。未来有必要进行研究以阐明潜在机制。
