Causal relationship between folic acid and prostate cancer risk: Insights from Mendelian randomization analysis

source extracted confidence: high 2026-04-09
#humans #male #dietary-supplements #folic-acid #genome-wide-association-study

Causal relationship between folic acid and prostate cancer risk: Insights from Mendelian randomization analysis

Guo et al., 2024 | Int J Urol | Meta Analysis

Citation

Guo Xiaoxiao, Zhang Fengbo, Hao Gangyue. Causal relationship between folic acid and prostate cancer risk: Insights from Mendelian randomization analysis. Int J Urol. 2024-Dec;31(12):1356-1364. doi:10.1111/iju.15565

Abstract

OBJECTIVE: Folic acid is a commonly used dietary supplement of trace element, but it may increase the risk of prostate cancer (PCa). The aim of this study was to investigate the causal relationship between PCa and folic acid supplementation, as well as dietary folate equivalents, using Mendelian randomization (MR) analysis. METHODS: The Genome-Wide Association Study (GWAS) data of folic acid supplementation and dietary folate equivalents were selected from UK Biobank. Meta-analysis of GWASs of PCa was obtained from PCa Association Group to Investigate Cancer-Associated Alterations in the Genome consortium. MR analysis was performed with inverse variance weighted (IVW) method, MR-Egger regression, simple mode, weighted median, and weighted mode analysis. Heterogeneity and horizontal pleiotropy tests and reverse MR analysis were conducted to assess the robustness and reliability of the causal inference. RESULTS: Six single nucleotide polymorphisms (SNPs) associated with folic acid supplementation and five SNPs associated with dietary folate equivalents were identified as instrumental variables. Genetically predicted folic acid supplementation was associated with an increased risk of PCa (OR 1.200, p < 0.001, by IVW method), and there was no evidence of heterogeneity, horizontal pleiotropy, or significant reverse causality (all p > 0.05). In contrast, dietary folate equivalents showed no significant correlation with PCa (p > 0.05 for all five MR methods). CONCLUSION: This study demonstrated an association between increased risk of PCa and folic acid supplementation, but not with dietary folate equivalents. These findings have implications for public health interventions and personalized preventive strategies for PCa.

Key Findings

Six single nucleotide polymorphisms (SNPs) associated with folic acid supplementation and five SNPs associated with dietary folate equivalents were identified as instrumental variables. Genetically predicted folic acid supplementation was associated with an increased risk of PCa (OR 1.200, p < 0.001, by IVW method), and there was no evidence of heterogeneity, horizontal pleiotropy, or significant reverse causality (all p > 0.05). In contrast, dietary folate equivalents showed no significant corr

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Male
  • Dietary Supplements
  • Folic Acid
  • Genome-Wide Association Study
  • Mendelian Randomization Analysis
  • Polymorphism, Single Nucleotide
  • Prostatic Neoplasms
  • Risk Factors

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis
  • Vertical: folate

Provenance

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