Impact of folate deficiency on DNA stability.
Level 5 - mechanism / opinion, no new human data
Narrative review summarizing in vitro, animal, and human mechanistic data without original human data or systematic methodology.
PubMed 12163709 · doi:10.1093/jn/132.8.2444S
What was done
The author reviewed evidence across in vitro, rodent in vivo, and human model systems addressing mechanisms linking folate deficiency with DNA instability and colorectal cancer, focusing on uracil misincorporation during DNA synthesis/repair and methylation changes via S-adenosylmethionine (SAM) depletion.
What was found
No quantitative findings or effect sizes are reported in the abstract. In vitro evidence supports that folate deficiency causes uracil misincorporation into DNA, leading to double-strand breaks and chromosomal damage, while also depleting cellular SAM and inducing DNA hypomethylation. In vivo rodent data are noted as difficult to interpret due to model variations and tissue specificity, and human data are influenced by nutrient-gene interactions and enzyme polymorphisms.
Why it matters
It provides a mechanistic framework for how low folate intake can lead to genomic instability and carcinogenesis, highlighting the role of genetic polymorphisms in modulating these pathways.
Limits
This is a narrative review with no quantitative human outcome data presented in the abstract. Rodent findings are limited by model heterogeneity and tissue-specific metabolism, while human evidence is heavily confounded by nutrient-gene interactions.
Cited by
- supports Folate deficiency causes DNA double-strand breaks that can lead to cancer-causing mutations.