Associations of serum cystatin C concentrations with total mortality and mortality of 12 site-specific cancers

Changzhi Huang; Jiayi Lu; Jing Yang; Zhenling Wang; Dong Hang; Zan Fu

doi:10.3389/fmolb.2024.1209349

Associations of serum cystatin C concentrations with total mortality and mortality of 12 site-specific cancers

Front Mol Biosci. 2024 Apr 25:11:1209349. doi: 10.3389/fmolb.2024.1209349. eCollection 2024.

Authors

Changzhi Huang^#¹, Jiayi Lu^#², Jing Yang^#², Zhenling Wang¹, Dong Hang^{2

3}, Zan Fu¹

Affiliations

¹ Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
² Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
³ Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.

^# Contributed equally.

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: UK Biobank; cancer; cystatin C; mortality; prospective cohort study.

Grants and funding

This study was funded by the National Natural Science Foundation of China (82172956 and 81973127), the Natural Science Foundation of Jiangsu Province (BK20190083), and the Qing Lan Project of Jiangsu Province. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.