title: Vitamin B-6 and colorectal cancer risk: a prospective population-based study using 3 distinct plasma markers of vitamin B-6 status.
abstract: Background:Higher plasma concentrations of the vitamin B-6 marker pyridoxal 5'-phosphate (PLP) have been associated with reduced colorectal cancer (CRC) risk. Inflammatory processes, including vitamin B-6 catabolism, could explain such findings.Objective:We investigated 3 biomarkers of vitamin B-6 status in relation to CRC risk.Design:This was a prospective case-control study of 613 CRC cases and 1190 matched controls nested within the Northern Sweden Health and Disease Study (n= 114,679). Participants were followed from 1985 to 2009, and the median follow-up from baseline to CRC diagnosis was 8.2 y. PLP, pyridoxal, pyridoxic acid (PA), 3-hydroxykynurenine, and xanthurenic acids (XAs) were measured in plasma with the use of liquid chromatography-tandem mass spectrometry. We calculated relative and absolute risks of CRC for PLP and the ratios 3-hydroxykynurenine:XA (HK:XA), an inverse marker of functional vitamin B-6 status, and PA:(PLP + pyridoxal) (PAr), a marker of inflammation and oxidative stress and an inverse marker of vitamin B-6 status.Results:Plasma PLP concentrations were associated with a reduced CRC risk for the third compared with the first quartile and for PLP sufficiency compared with deficiency [OR: 0.60 (95% CI: 0.44, 0.81) and OR: 0.55 (95% CI: 0.37, 0.81), respectively]. HK:XA and PAr were both associated with increased CRC risk [OR: 1.48 (95% CI: 1.08, 2.02) and OR: 1.50 (95% CI: 1.10, 2.04), respectively] for the fourth compared with the first quartile. For HK:XA and PAr, the findings were mainly observed in study participants with <10.5 y of follow-up between sampling and diagnosis.Conclusions:Vitamin B-6 deficiency as measured by plasma PLP is associated with a clear increase in CRC risk. Furthermore, our analyses of novel markers of functional vitamin B-6 status and vitamin B-6-associated oxidative stress and inflammation suggest a role in tumor progression rather than initiation.
authors.affiliation: Departments of Medical Biosciences, Pathology.
authors.forename: Björn
authors.initials: B
authors.lastname: Gylling
authors.affiliation: Radiation Sciences, Oncology.
authors.forename: Robin
authors.initials: R
authors.lastname: Myte
authors.affiliation: Clinical Pharmacology, Pharmacology and Clinical Neurosciences.
authors.forename: Jörn
authors.initials: J
authors.lastname: Schneede
authors.affiliation: Biobank Research, Public Health and Clinical Medicine.
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.affiliation: Statistics, Umeå School of Business and Economics, and.
authors.forename: Jenny
authors.initials: J
authors.lastname: Häggström
authors.affiliation: Odontology, Cariology, Umeå University, Umeå, Sweden.
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Johansson
authors.affiliation: Bevital AS, Bergen, Norway; and.
authors.forename: Arve
authors.initials: A
authors.lastname: Ulvik
authors.affiliation: Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.affiliation: Radiation Sciences, Oncology.
authors.forename: Bethany
authors.initials: B
authors.lastname: Van Guelpen
authors.affiliation: Departments of Medical Biosciences, Pathology, richard.palmqvist@umu.se.
authors.forename: Richard
authors.initials: R
authors.lastname: Palmqvist
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000209:etiology* / Q000517:prevention & control; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D016017:Odds Ratio; D018384:Oxidative Stress; D011446:Prospective Studies; D011730:Pyridoxal / Q000097:blood; D011732:Pyridoxal Phosphate / Q000097:blood; D011735:Pyridoxic Acid / Q000097:blood; D013548:Sweden; D025101:Vitamin B 6 / Q000097:blood*; D026681:Vitamin B 6 Deficiency / Q000097:blood / Q000150:complications*; D014977:Xanthurenates / Q000097:blood*
chemical_list: D015415:Biomarkers; D014977:Xanthurenates; C005045:3-hydroxykynurenine; D007737:Kynurenine; D011730:Pyridoxal; C028330:xanthurenic acid; D011735:Pyridoxic Acid; D011732:Pyridoxal Phosphate; D025101:Vitamin B 6
keywords: biomarkers; colorectal cancer; inflammation; metabolite ratios; vitamin B-6