High levels of folate from supplements and fortification are not associated with increased risk of colorectal cancer.

Gastroenterology
Q1
Jul 2011
Citations:92
Influential Citations:2
Observational Studies (Human)
80
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Methods
Design: Prospective cohort study using the CPS-II Nutrition Cohort. Participants: 99,523 adults (43,512 men, 56,011 women) aged 50-74 at enrollment; cancer-free at baseline (except nonmelanoma skin cancer); follow-up from 1999 to June 30, 2007. Folate exposure assessed in 1999 via a 152-item semi-quantitative FFQ, capturing natural folate from foods, folic acid from fortification and supplements, and total folate expressed as dietary folate equivalents. Analytic cohort comprised after applying exclusions; 1,023 incident colorectal cancers were identified (526 men, 497 women). Cases verified via medical records, state registries, and death data. Cox proportional hazards regression adjusted for multiple covariates.
Results
In the postfortification era, higher total folate intake is associated with lower colorectal cancer risk. Highest vs lowest quintile of total folate intake: RR 0.81 (95% CI 0.66-0.99; P trend 0.047). Natural folate and dietary folate were not significantly associated; folic acid showed weaker or non-significant associations overall. Inverse associations were stronger after excluding the first 2 years of follow-up and among those with prior endoscopy. No evidence that fortification or supplementation increases colorectal cancer risk. Total folate is the best overall exposure metric because it captures all forms and sources.
Limitations
Observational design with potential residual confounding; folate intake measured by FFQ with measurement error; modest correlation between FFQ folate intake and erythrocyte folate; follow-up period may not fully capture long-latency effects; cohort comprises relatively healthier individuals, limiting generalizability; possible unmeasured confounding.

Abstract

BACKGROUND & AIMS Folate intake has been inversely associated with colorectal cancer risk in several prospective epidemiologic studies. However, no study fully assessed the influence of the high levels of folate that are frequently consumed in the Un...