Abstract
Abstract Background: Cancer patients are highly concerned about food choices and dietary supplements that may affect their treatment outcomes. Excess folic acid (synthetic folate) from supplements or fortification can lead to accumulation of unmetabolized folic acid in the systemic circulation and urine, and may promote cancer growth, especially among those with neoplastic alterations. Objective: We investigated the prospective association between synthetic versus natural folate intake and clinical outcomes in non-muscle-invasive bladder cancer (NMIBC), which is a highly recurrent disease. Design: In a cohort of 619 NMIBC patients, folate intake at diagnosis was assessed with a previously validated food frequency questionnaire and categorized according to tertiles. After a median follow-up of 5.2 years, 303 tumor recurrence and 108 progression events were documented from medical record review. Multivariable Cox proportional hazards and logistic models were used to estimate adjusted hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals (95% CI). Results: Synthetic folic acid intake was positively associated with risk of recurrence among NMIBC patients (medium vs. low intake: HR=1.72; 95% CI=1.20, 2.48; P=0.003; high vs. low intake: HR=1.80; 95% CI=1.14, 2.84; P=0.01). Patients with higher folic acid intake were more likely to have multifocal tumors at diagnosis (medium/high vs. low: OR=2.08; 95% CI=1.08, 4.02; P=0.03). In contrast, natural folate intake tended to be inversely associated with risk of progression (medium/high vs. low: HR=0.68; 95% CI=0.44, 1.04; P=0.08). Conclusions: High intake of synthetic folic acid, in contrast to the natural forms, is associated with increased risk of recurrence in NMIBC and multifocal tumors at diagnosis, suggesting that folic acid may be unsafe for NMIBC patients. These findings provide some evidence for nutritional consultation regarding folate intake among NMIBC patients. Citation Format: Huakang Tu, Colin P. Dinney, Yuanqing Ye, Barton H. Grossman, Seth P. Lerner, Xifeng Wu. Is folic acid safe for non-muscle-invasive bladder cancer patients? An evidence-based cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2239.
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