There are suggestions of an inverse association between
folate intake and serum
folate levels and the risk of oral cavity and
pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary
folate. Our study aims to investigate the association between
folate intake and the risk of OPC within the International
Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from ten case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (
ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total
folate intake (natural, fortification and supplementation) and natural
folate only, and OPC risk. We found an inverse association between total
folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43-0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43-0.75). A similar inverse association, though somewhat weaker, was observed for
folate intake from natural sources only in oral cavity
cancer (OR = 0.64, 95% CI: 0.45-0.91). The highest OPC risk was observed in heavy alcohol drinkers with low
folate intake as compared to never/light drinkers with high
folate (OR = 4.05, 95% CI: 3.43-4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4-20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34-3.19) for those ever tobacco users with low
folate intake, compared with nevere tobacco users and high
folate intake (AP of interaction =10.6%, 95% CI: 0.41-20.8%). Our project of a large pool of case-control studies supports a protective effect of total
folate intake on OPC risk.