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.