The Mediating Role of Comorbidities on the Relationship Between Serum Vitamin D and Five-Year Mortality Risk in Colon Cancer Patients

Abstract

This retrospective cohort study explores the relationship between vitamin D levels and 5-year mortality risk among 1,549 colon cancer patients seen at University of California health centers between 2012 and 2019, with a particular focus on the mediating role of comorbidities. Methods leveraged structural equation modeling to assess both direct and indirect pathways linking vitamin D to mortality risk. This analysis revealed a protective direct effect of higher vitamin D levels against mortality risk. Additionally, this study uncovered an indirect pathway, demonstrating that vitamin D lowers mortality risk by mitigating comorbidity, which subsequently influence mortality risk. Study results indicate that approximately 9.2% of the beneficial effect of vitamin D on mortality risk is attributable to its capacity to reduce comorbidity burden. In disaggregated and confounder-adjusted structural modeling, there were significant indirect effects for 25(OH)D on mortality risk through its effects on depression and obesity but not on anxiety, diabetes, or chronic kidney disease. These results suggest that the protective effects of vitamin D in colon cancer etiology appear to be through direct action on cancer progression, though patients who also suffer from depression and obesity would especially benefit from achieving adequate levels of serum vitamin D.