The impact of folate intake on the risk of head and neck cancer in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) cohort

Prospective cohort within the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial; 101,700 participants aged 55–74; both sexes; cancer-free at baseline; dietary folate intake assessed via Diet History Questionnaire; follow-up median 12.5 years; 186 incident head and neck cancer cases; multivariable Cox proportional hazards models adjusting for age, sex, BMI, education, race, smoking, alcohol, and total fruit and vegetable intake.

Higher intake of food folate and fortified folic acid from foods was associated with a dose-dependent reduction in head and neck cancer risk. Highest vs lowest quartiles: food folate HR 0.35 (95% CI 0.18–0.67); fortified folic acid HR 0.49 (95% CI 0.30–0.82). Total folate, natural folate, and supplemental folic acid showed no significant associations with risk. No significant interactions with smoking or alcohol intake observed. Conclusion: Dietary folate from foods and fortified sources may protect against head and neck cancer; supplemental folic acid showed no protective effect in this cohort.

Limited statistical power for subsite analyses due to a relatively small number of HNC cases in some subsites; observational design with potential residual confounding; dietary intake assessed only at baseline, not accounting for dietary changes over time; lack of data on HPV status and genetic variants related to one-carbon metabolism; results primarily reflect findings in a US population.