• Division of Public Health, Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108, USA.
• Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84108, USA.
• Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan 520133, Italy.

BACKGROUND: Although low levels of folate leads to disturbances in DNA replication, DNA methylation and DNA repair, the association between dietary folate intake and head and neck cancer (HNC) risk remains unclear.

METHODS: We evaluated the association between folate intake and HNC risk using prospective cohort data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. This study included 101 700 participants and 186 cases with confirmed incident HNC. The median follow-up was 12.5 years. We estimated hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) using Cox proportional hazard model including age, sex, body mass index, education, race, tobacco smoking, alcohol drinking and total fruit and vegetable intake.

RESULTS: Higher intake of food folate and fortified folic acid in foods was associated with a decreasing HNC risk in a dose-response manner. The HRs of highest vs the lowest quartile of intake were 0.35 (95%CI: 0.18-0.67) for food folate, and 0.49 (95%CI: 0.30-0.82) for fortified folic acid. Intakes of total folate, natural folate and supplemental folic acid were not associated with the risk of HNC and its subsites. We did not detect any interaction between smoking, drinking and food folate intake on HNC risk.

CONCLUSIONS: These findings provide evidence of the protective role of dietary folate intake on HNC risk.