Prognostic significance of the CALLY index for cancer risk and survival: evidence from NHANES 2001–2018

BACKGROUND: The C-reactive protein-albumin-lymphocyte (CALLY) index is an immune-nutritional biomarker associated with cancer prognosis. Its relevance to cancer incidence and long-term survival in the general population has not been well established. METHODS: We analyzed NHANES 2001-2018 data from 36,904 participants, including 3,218 cancer patients. Logistic regression assessed cancer risk, and Cox proportional hazards models evaluated all-cause, cancer-specific, and cardiovascular mortality among cancer survivors. Restricted cubic splines (RCS) examined nonlinear associations, and subgroup analyses were stratified by age and sex. RESULTS: Cancer patients showed lower CALLY index values. Compared with the lowest quartile, the highest quartile was associated with a reduced risk of cancer (OR = 0.77, 95% CI = 0.67-0.90, P < 0.001). RCS identified a nonlinear association with cancer incidence (P-nonlinearity = 0.003), with a threshold at 9.402 (log-transformed). Among survivors, higher CALLY index values were significantly associated with reduced all-cause (HR = 0.39), cancer-cause mortality (HR = 0.36), and cardiovascular mortality (HR = 0.32), all P < 0.001. These associations remained consistent across subgroups. CONCLUSIONS: The CALLY index is significantly associated with cancer risk and mortality. As a simple and robust biomarker reflecting immune-nutritional status, it may be associated with cancer risk and could provide useful information for prognostic assessment. Although causal inferences cannot be drawn due to the cross-sectional design of NHANES.