One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk |
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| Authors: | Björn Gylling Robin Myte Arve Ulvik Per M Ueland Øivind Midttun Jörn Schneede Göran Hallmans Jenny Häggström Ingegerd Johansson Bethany Van Guelpen Richard Palmqvist |
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| Institution: | 1. Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden;2. Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden;3. Bevital AS, Laboratory building, Bergen, Norway;4. Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway;5. Department of Clinical Pharmacology, Pharmacology and Clinical Neurosciences, Umeå University, Umeå, Sweden;6. Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden;7. Department of Statistics, Umeå School of Business and Economics, Umeå University, Umeå, Sweden;8. Department of Odontology, Cariology, Umeå University, Umeå, Sweden |
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| Abstract: | One-carbon metabolism biomarkers are easily measured in plasma, but analyzing them one at a time in relation to disease does not take into account the interdependence of the many factors involved. The relative dynamics of major one-carbon metabolism branches can be assessed by relating the functional B-vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs. We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre) and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk. Furthermore, the relative contribution of potential confounders to the variance of the ratio-based B-vitamin markers was calculated by linear regression in a nested case–control study of 613 CRC cases and 1,190 matched controls. Total B-vitamin status was represented by a summary score comprising Z-standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5′-phosphate and riboflavin. Associations with CRC risk were estimated using conditional logistic regression. We found that the ratio-based B-vitamin markers all outperformed tHcy as markers of total B-vitamin status, in both CRC cases and controls. In addition, associations with CRC risk were similar for the ratio-based B-vitamin markers and total B-vitamin status (approximately 25% lower risk for high vs. low B-vitamin status). In conclusion, ratio-based B-vitamin markers were good predictors of total B-vitamin status and displayed similar associations as total B-vitamin status with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice. |
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| Keywords: | biomarkers colorectal cancer biochemistry homocysteine |
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