Folate exposures and risk of colorectal cancer: an umbrella review of meta-analyses of observational studies and randomised controlled trials

source extracted confidence: high 2026-04-09
#humans #folic-acid #colorectal-neoplasms #randomized-controlled-trials-as-topic #observational-studies-as-topic

Folate exposures and risk of colorectal cancer: an umbrella review of meta-analyses of observational studies and randomised controlled trials

Li et al., 2025 | BMJ Open | Systematic Review

Citation

Li Tongtong, Yin Lina, ... Huang Guowei. Folate exposures and risk of colorectal cancer: an umbrella review of meta-analyses of observational studies and randomised controlled trials. BMJ Open. 2025-Nov-28;15(11):e103637. doi:10.1136/bmjopen-2025-103637

Abstract

OBJECTIVES: To systematically summarise and evaluate the existing evidence of the associations between diverse folate exposures and the risk of colorectal cancer (CRC), while identifying evidence quality. DESIGN: Umbrella review of meta-analyses. DATA SOURCES: PubMed, Web of Science, Cochrane and Embase were searched from the database inception to March 2024, with an update to 12 October 2025. ELIGIBILITY CRITERIA: We included meta-analyses of randomised controlled trials or observational studies that investigated the associations between folate exposures and CRC or precancerous lesions (ie, adenoma and polyps). DATA EXTRACTION AND SYNTHESIS: For each association, we recalculated the summary effect size with 95% CI using the DerSimonian and Laird random-effects model, heterogeneity (I² statistic), 95% prediction interval, small-study effect (Egger's test) and excess significance bias (χ² test). RESULTS: This umbrella review included five meta-analyses describing 10 associations between folate exposures and CRC risk. In the general population, moderate-quality evidence supported an inverse association between total folate intake (from foods and supplements) and CRC risk (RR 0.84; 95% CI 0.80 to 0.90), while low-quality evidence suggested inverse associations of dietary folate intake (from foods alone) (RR 0.88; 95% CI 0.81 to 0.96) and folic acid supplement intake (RR 0.83; 95% CI 0.77 to 0.90) with CRC risk. Among patients with inflammatory bowel disease, low-quality evidence suggested an inverse association between folic acid supplement intake and CRC incidence (HR 0.71; 95% CI 0.53 to 0.96). Additionally, elevated circulating folate levels were observed to have a provoking effect on advanced-stage tumours (OR 1.95; 95% CI 1.18 to 3.22; Grading of Recommendations Assessment, Development and Evaluation (GRADE): very low). Sensitivity analysis revealed a potential increased risk of adenoma recurrence associated with folic acid supplement use among patients with a history of adenoma (RR 1.05; 95% CI 0.86 to 1.29; GRADE: high). CONCLUSIONS: These findings suggest that consuming dietary folate and total folate intake may be beneficial in CRC primary prevention. Specifically, folic acid supplements may inhibit colorectal carcinogenesis in normal tissues while promoting cancer in the established neoplastic foci. PROSPERO REGISTRATION NUMBER: CRD42024537550.

Key Findings

This umbrella review included five meta-analyses describing 10 associations between folate exposures and CRC risk. In the general population, moderate-quality evidence supported an inverse association between total folate intake (from foods and supplements) and CRC risk (RR 0.84; 95% CI 0.80 to 0.90), while low-quality evidence suggested inverse associations of dietary folate intake (from foods alone) (RR 0.88; 95% CI 0.81 to 0.96) and folic acid supplement intake (RR 0.83; 95% CI 0.77 to 0.90)

Outcomes Measured

  • inflammatory markers

Population

Field Value
Population inflammatory bowel disease
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Folic Acid
  • Colorectal Neoplasms
  • Randomized Controlled Trials as Topic
  • Observational Studies as Topic
  • Dietary Supplements
  • Risk Factors
  • Meta-Analysis as Topic

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review
  • Vertical: folate-cancer

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09