Joint association of cadmium exposure and inflammatory indicators with mortality in US cancer survivors

Abstract Background Cadmium (Cd) exposure and high inflammation status are independent risk factors for mortality in cancer survivors, yet their combined impact on mortality remains unexplored. The objective of this study was to investigate joint effect of cadmium exposure and complete blood cell count (CBC)-derived inflammation markers on mortality in cancer survivors. Methods This study utilized information collected from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2007 to 2018, with a participant pool of 2,450 individuals who had survived cancer. Blood cadmium levels and inflammation markers derived from CBC were systematically evaluated. We used weighted multivariable Cox regression models to evaluate the joint effect of blood cadmium levels and inflammation markers on all-cause mortality. Survival probabilities under different exposure conditions were compared using Kaplan-Meier curves. To investigate the independent effects of blood cadmium levels and inflammatory indicators on mortality, restricted cubic spline curve (RCS) modeling was used. Additionally, subgroup analyses were further conducted by age, sex, hypertension status, diabetes, smoking history, alcohol consumption, and other factors to explore potential interactions across different populations. Results Over a median follow-up period of 77 months, a total of 608 deaths were documented. The results showed that the combined exposure to elevated cadmium levels and high inflammatory markers was significantly associated with increased mortality risk. Notably, the highest mortality risk was observed in participants with both high cadmium levels and elevated MLR (hazard ratio [HR] = 3.12; 95% confidence interval [CI],2.07–4.72). Kaplan-Meier curves further demonstrated the poorest survival outcomes in subgroups with concurrent high cadmium exposure and elevated inflammatory indices. RCS analysis revealed significant linear associations between several inflammatory markers (including PIV, MLR, NLR) and all-cause mortality, whereas PLR, SII, SIRI, and blood cadmium levels exhibited nonlinear relationships with all-cause mortality. These findings were consistently supported by subgroup analyses. Conclusion This study represents the first systematic investigation evaluating the combined impact of cadmium exposure and inflammatory markers on mortality risk among cancer survivors. Our findings suggest that the joint effect of cadmium exposure and systemic inflammation significantly impacts survival outcomes in this population, providing novel perspectives for personalized interventions in this population.