title: 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.
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
authors.forename: Robin
authors.initials: R
authors.lastname: Myte
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Gylling
authors.affiliation: Department of Statistics, Umeå School of Business and Economics, Umeå University, Umeå, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Häggström
authors.affiliation: Department of Clinical Pharmacology, Pharmacology and Clinical Neurosciences, Umeå University, Umeå, Sweden.
authors.forename: Jörn
authors.initials: J
authors.lastname: Schneede
authors.affiliation: Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
authors.forename: Per
authors.initials: P
authors.lastname: Magne Ueland
authors.affiliation: Department of Biobank Research, Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.affiliation: Department of Odontology, Cariology, Umeå University, Umeå, Sweden.
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Johansson
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: Richard
authors.initials: R
authors.lastname: Palmqvist
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
authors.forename: Bethany
authors.initials: B
authors.lastname: Van Guelpen
mesh_terms: D000328:Adult; D000368:Aged; D001499:Bayes Theorem; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002244:Carbon / Q000378:metabolism; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006801:Humans; D000069550:Machine Learning; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012256:Riboflavin / Q000097:blood*; D012307:Risk Factors; D025101:Vitamin B 6 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D002244:Carbon; D025101:Vitamin B 6; D005492:Folic Acid; D012256:Riboflavin