Association of folate intake and colorectal cancer risk in the postfortification era in US women

Background: Folate may play a preventive role in the early stages of colorectal carcinogenesis, but long latencies may be needed to observe a reduction in colorectal cancer (CRC) incidence. In addition, concerns have been raised about the potential for cancer promotion with excessive folate intake, especially after the mandatory folic acid fortification in the United States in 1998. Objective: We aimed to examine the association between folate intake in different chemical forms and CRC risk, especially in the postfortification era in the United States. Design: We prospectively followed 86,320 women from the Nurses' Health Study (1980-2016). Folate intake was collected by validated food frequency questionnaires. CRC was self reported and confirmed by review of medical records. The association between the folate intake and CRC risk was assessed using Cox proportional hazards regression. Results: We documented 1988 incident CRC cases during follow-up. Analyzing folate intake as a continuous variable, greater total folate intake 12-24 y before diagnosis was associated with lower risk of CRC (per increment of 400 dietary folate equivalents (DFE)/d, HR: 0.93, 95% CI: 0.85, 1.01 for 12-16 y; HR: 0.83, 95% CI: 0.75, 0.92 for 16-20 y: and HR: 0.87, 95% 0: 0.77, 0.99 for 20-24 y); and greater synthetic folic acid intake 16-24 y before diagnosis was also associated with a lower CRC risk (per increment of 400 DFE/d, HR: 0.91, 95% CI: 0.84, 0.99 for 16-20 y and HR: 0.91, 95% CI: 0.83-1.01 for 20-24 y). In the postfortification period (1998-2016). intake of total or specific forms of folate was not associated with CRC risk, even among multivitamin users. Conclusions: Folate intake, both total and from synthetic forms. was associated with a lower risk of overall CRC after long latency periods. There was no evidence that high folate intake in the postfortification period was related to increased CRC risk in this US female population.