Abstract
BACKGROUND: Patients with arthritis exhibit abnormal serum folate concentrations and have a higher incidence of cancer. The aim of this study was to investigate the association of serum folate concentrations with cancer mortality among individuals with arthritis. METHODS: This cohort study included 7,514 patients with arthritis from National Health and Nutrition Examination Survey (NHANES) 1999 to 2016 and NHANES III (1988-1994). Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Serum folate concentrations were categorized into 4 groups, group 1 (≤ 17 nmol/L); group 2 (17-≤34 nmol/L); group 3 (34-≤51 nmol/L); and group 4 (> 51 nmol/L). Cox regression models were used to calculate hazard ratios and 95% confidence intervals for the associations between folate concentrations and the risk of mortality. RESULTS: During a median follow-up of 9.75 [interquartile range, IQR, 5.75-14.5] years, there were 2,602 all-cause deaths, 949 deaths due to cardiovascular disease, and 478 deaths due to cancer. A non-linear association was observed for folate concentrations with the risk of cancer mortality (P < 0.001) among arthritis patients. Compared with the reference group 2, the hazard ratios for cancer mortality were 1.75 (95% CI, 1.15-2.69) in group 1, 1.70 (95% CI, 1.17-2.46) in group 3, and 1.60 (95% CI, 1.13-2.25) in group 4. CONCLUSIONS: This study shows that both low and high levels of serum folate are associated with an increased risk of cancer mortality among individuals with arthritis, indicating a potential beneficial role of maintaining moderate serum folate concentrations in decreasing the risk of cancer mortality among this population.