Association of serum folate levels with mortality among cancer survivors: insights from NHANES 1999-2018.
BACKGROUND Previous studies on folate and cancer-related outcomes have reported inconsistent findings. This study examined the association between serum folate levels and mortality among cancer survivors using National Health and Nutrition Examination Survey (NHANES) 1999-2018 data. METHODS We included 3524 cancer survivors aged ≥20 years with available serum folate and mortality data. Because of its right-skewed distribution, serum folate was log2-transformed and analyzed as both a continuous variable and quartiles. Quartiles were generated based on the distribution of log2-transformed serum folate in the final analytic sample. Cox proportional hazards models were used to estimate associations with all-cause, cancer-specific, and cardiovascular disease (CVD) mortality, adjusting for demographic, socioeconomic, lifestyle, and clinical covariates. RESULTS In the fully adjusted model, log2-transformed serum folate was inversely associated with all-cause mortality during follow-up (HR = 0.89, 95% CI: 0.83-0.96, P < 0.01). Compared with Q3, participants in the lowest quartile had higher risks of all-cause mortality (HR = 1.52, 95% CI: 1.26-1.83, P < 0.001), cancer-specific mortality (HR = 2.03, 95% CI: 1.44-2.87, P < 0.001), and CVD mortality (HR = 1.60, 95% CI: 1.04-2.44, P = 0.03). The highest quartile showed a higher crude mortality proportion than Q3 and was not associated with lower mortality after full adjustment. CONCLUSIONS Lower serum folate levels were associated with increased mortality among cancer survivors. The findings suggest a non-linear pattern, with more favorable outcomes at intermediate folate levels and no additional benefit at higher levels. Further prospective studies are needed to confirm these associations.