Sex-specific association of serum cystatin C with the risks of 24 type of cancer: pan-cancer analyses in the UK Biobank

Background: We aim to investigate the associations of circulating cystatin C (Cyst-C) concentrations with the risk of different cancers in men and women, using a pan-cancer approach, including 24 cancers in UK Biobank. Methods: A total of 421,867 cancer-free participants from the UK Biobank study were included. We restricted analyses to cancers with a minimum of 100 recorded cases in men or women. Results: During a median follow-up of 10.7 years, in both men and women, circulating Cyst-C concentrations (per standard deviation [SD] increment) were significantly and positively associated with the risks of kidney cancer, lung cancer, leukemia, mesothelial and soft tissue cancer, multiple myeloma, non-Hodgkin lymphoma and liver cancer, with a range of adjusted hazard ratios (HR) from 1.09 (95% confidence interval [CI]: 1.01–1.18) for kidney cancer in women to 1.27 (95% CI: 1.17–1.38) for liver cancer in women. In addition, only in men, higher Cyst-C concentrations (per SD increment) were associated with higher risks of head and neck cancer (adjusted HR, 1.10; 95% CI: 1.02–1.21), esophagus cancer (adjusted HR, 1.09; 95% CI: 1.01–1.17), and pancreas cancer (adjusted HR, 1.15; 95% CI: 1.07–1.24), as well as a lower risk of prostate cancer (adjusted HR, 0.95; 95% CI: 0.93–0.98). Meanwhile, only in women, higher Cyst-C concentrations (per SD increment) were related to higher risks of brain or central nervous system or intracranial cancer (adjusted HR, 1.18; 95% CI: 1.09–1.27) and urinary tract cancer (adjusted HR, 1.10; 95% CI: 1.02–1.19). Conclusions: Circulating Cyst-C was significantly associated with multiple human cancers in men or women. Our results suggest that circulating Cyst-C may serve as a potential biomarker for identifying multiple human cancers.