ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2008
Mathematical modeling of folate metabolism: predicted effects of genetic polymorphisms on mechanisms and biomarkers relevant to carcinogenesis.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Pooled it
- Modeling mechanisms of in vivo variability in methotrexate accumulation and folate pathway inhibition in acute lymphoblastic leukemia cells.PLoS computational biology · 2010Trial
- Genome-wide association study of circulating folate one-carbon metabolites.Genetic epidemiology · 2019Article
- Neuro-fuzzy model of homocysteine metabolism.Journal of genetics · 2017Article
- Clinical Utility of Serum Homocysteine and Folate as Tumor Markers in Oral Squamous Cell Carcinoma - A Cross-Sectional Study.Journal of clinical and diagnostic research : JCDR · 2016Article
- A Mendelian Randomization Study of Plasma Homocysteine and Multiple Myeloma.Scientific reports · 2016Article
- Red blood cell folate and plasma folate are not associated with risk of incident colorectal cancer in the Women's Health Initiative observational study.International journal of cancer · 2015Observational
- A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk.European journal of epidemiology · 2013Article
- A population model of folate-mediated one-carbon metabolism.Nutrients · 2013Article
- Folate metabolite profiling of different cell types and embryos suggests variation in folate one-carbon metabolism, including developmental changes in human embryonic brain.Molecular and cellular biochemistry · 2013Article
- Personalised nutrition: how far has nutrigenomics progressed?European journal of clinical nutrition · 2013Review
- The relationship between intracellular and plasma levels of folate and metabolites in the methionine cycle: a model.Molecular nutrition & food research · 2013Article
- Molecular mechanisms underlying the potentially adverse effects of folate.Clinical chemistry and laboratory medicine · 2013Review
- Mathematical modeling predicts the effect of folate deficiency and excess on cancer-related biomarkers.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2011Article
- Proteomics and systems biology: current and future applications in the nutritional sciences.Advances in nutrition (Bethesda, Md.) · 2011Review
- Variation in folate pathway genes and distal colorectal adenoma risk: a sigmoidoscopy-based case-control study.Cancer causes & control : CCC · 2011Article
- A genetic signature of spina bifida risk from pathway-informed comprehensive gene-variant analysis.PloS one · 2011Article
- Plasma vitamins B2, B6, and B12, and related genetic variants as predictors of colorectal cancer risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2010Article
- Gene--environment-wide association studies: emerging approaches.Nature reviews. Genetics · 2010Review
- Methods for investigating gene-environment interactions in candidate pathway and genome-wide association studies.Annual review of public health · 2010Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Low-folate status and genetic polymorphisms in folate metabolism have been linked to several cancers. Possible biological mechanisms for this association include effects on purine and thymidine synthesis, DNA methylation, or homocysteine concentrations. The influence of genetic variation in folate metabolism on these putative mechanisms or biomarkers of cancer risk has been largely unexplored. We used a mathematical model that simulates folate metabolism biochemistry to predict (a) the effects of polymorphisms with defined effects on enzyme function (MTHFR and TS) and (b) the effects of potential, as-of-yet-unidentified polymorphisms in a comprehensive set of folate-metabolizing enzymes on biomarkers and mechanisms related to cancer risk. The model suggests that there is substantial robustness in the pathway. Our predictions were consistent with measured effects of known polymorphisms in MTHFR and TS on biomarkers. Polymorphisms that alter enzyme function of FTD, FTS, and MTCH are expected to affect purine synthesis, FTS more so under a low-folate status. In addition, MTCH polymorphisms are predicted to influence thymidine synthesis. Polymorphisms in methyltransferases should affect both methylation rates and thymidylate synthesis. Combinations of polymorphisms in MTHFR, TS, and SHMT are expected to affect nucleotide synthesis in a nonlinear fashion. These investigations provide information on effects of genetic polymorphisms on biomarkers, including those that cannot be measured well, and highlight robustness and sensitivity in this complex biological system with regard to genetic variability. Although the proportional changes in biomarkers of risk with individual polymorphisms are frequently small, they may be quite relevant if present over an individual's lifetime.
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