Dataset Information

Untangling the role of one-carbon metabolism in colorectal cancer risk: a comprehensive Bayesian network analysis.

ABSTRACT: The role of one-carbon metabolism (1CM), particularly folate, in colorectal cancer (CRC) development has been extensively studied, but with inconclusive results. Given the complexity of 1CM, the conventional approach, investigating components individually, may be insufficient. We used a machine learning-based Bayesian network approach to study, simultaneously, 14 circulating one-carbon metabolites, 17 related single nucleotide polymorphisms (SNPs), and several environmental factors in relation to CRC risk in 613 cases and 1190 controls from the prospective Northern Sweden Health and Disease Study. The estimated networks corresponded largely to known biochemical relationships. Plasma concentrations of folate (direct), vitamin B6 (pyridoxal 5-phosphate) (inverse), and vitamin B2 (riboflavin) (inverse) had the strongest independent associations with CRC risk. Our study demonstrates the importance of incorporating B-vitamins in future studies of 1CM and CRC development, and the usefulness of Bayesian network learning for investigating complex biological systems in relation to disease.

SUBMITTER: Myte R

PROVIDER: S-EPMC5324061 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Untangling the role of one-carbon metabolism in colorectal cancer risk: a comprehensive Bayesian network analysis.

Myte Robin R Gylling Björn B Häggström Jenny J Schneede Jörn J Magne Ueland Per P Hallmans Göran G Johansson Ingegerd I Palmqvist Richard R Van Guelpen Bethany B

Scientific reports 20170224

The role of one-carbon metabolism (1CM), particularly folate, in colorectal cancer (CRC) development has been extensively studied, but with inconclusive results. Given the complexity of 1CM, the conventional approach, investigating components individually, may be insufficient. We used a machine learning-based Bayesian network approach to study, simultaneously, 14 circulating one-carbon metabolites, 17 related single nucleotide polymorphisms (SNPs), and several environmental factors in relation t ...[more]

PMID: 28233834

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Project description:Investigations of folate-mediated one-carbon metabolism (FOCM) genes and gene-nutrient interactions with respect to colorectal cancer (CRC) risk are limited to candidate polymorphisms and dietary folate. This study comprehensively investigated associations between genetic variants in FOCM and CRC risk and whether the FOCM nutrient status modified these associations.Two hundred eighty-eight candidate and tagging single-nucleotide polymorphisms (SNPs) in 30 FOCM genes were genotyped for 821 incident CRC case-control matched pairs in the Women's Health Initiative Observational Study cohort. FOCM biomarkers (red blood cell [RBC] folate, plasma folate, pyridoxal-5'-phosphate [PLP], vitamin B12, and homocysteine) and self-reported alcohol consumption were measured at the baseline. Conditional logistic regression was implemented; effect modification was examined on the basis of known enzyme-nutrient relations.Statistically significant associations were observed between CRC risk and functionally defined candidate SNPs of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1; K134R), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR; P450R), and PR domain containing 2 with ZNF domain (PRDM2; S450N) and a literature candidate SNP of thymidylate synthase (TYMS; g.676789A>T; nominal P?<?.05). In addition, suggestive associations were noted for tagging SNPs in cystathionine-?-synthase (CBS), dihydrofolate reductase (DHFR), DNA (cytosine-5-)-methyltransferase 3? (DNMT3B), methionine adenosyltransferase I ? (MAT1A), MTHFD1, and MTRR (nominal P?<?.05; adjusted P, not significant). Significant interactions between nutrient biomarkers and candidate polymorphisms were observed for 1) plasma/RBC folate and folate hydrolase 1 (FOLH1), paraoxonase 1 (PON1), transcobalamin II (TCN2), DNMT1, and DNMT3B; 2) plasma PLP and TYMS TS3; 3) plasma B12 and betaine-homocysteine S-methyltransferase 2 (BHMT2); and 4) homocysteine and methylenetetrahydrofolate reductase (MTHFR) and alanyl-transfer RNA synthetase (AARS).Genetic variants in FOCM genes are associated with CRC risk among postmenopausal women. FOCM nutrients continue to emerge as effect modifiers of genetic influences on CRC risk.

Dataset Information

Untangling the role of one-carbon metabolism in colorectal cancer risk: a comprehensive Bayesian network analysis.

Publications

Untangling the role of one-carbon metabolism in colorectal cancer risk: a comprehensive Bayesian network analysis.

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