| 1. |
- de Vogel, Stefan, et al.
(författare)
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Biomarkers related to one-carbon metabolism as potential risk factors for distal colorectal adenomas
- 2011
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:8, s. 1726-1735
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Efficient one-carbon metabolism, which requires adequate supply of methyl group donors and B-vitamins, may protect against colorectal carcinogenesis. However, plasma folate and vitamins B2 and B12 have inconsistently been associated with colorectal cancer risk, and there have been no previous studies relating plasma concentrations of methionine, choline, and betaine to this outcome.METHODS: This study comprised 10,601 individuals, 50 to 64 years of age, participating in the Norwegian Colorectal Cancer Prevention (NORCCAP) screening study. Using logistic regression analyses, we crosssectionally investigated associations between distal colorectal adenoma occurrence-potential precursor lesions of colorectal carcinomas-and plasma concentrations of methyl group donors and B-vitamins, and polymorphisms of genes related to one-carbon metabolism.RESULTS: Screening revealed 1,809 subjects (17.1%) with at least one adenoma. The occurrence of high-risk adenomas (observed in 421 subjects) was inversely associated with plasma concentrations of methionine (highest versus lowest quartile: odds ratio (OR) = 0.61; 95% confidence interval (CI) = 0.45-0.83), betaine: OR = 0.74; 95% CI = 0.54-1.02, the vitamin B2 form flavin-mononucleotide (FMN): OR = 0.65; 95% CI = 0.49-0.88, and the vitamin B6 form pyridoxal 5'-phosphate (PLP): OR = 0.69; 95% CI = 0.51-0.95, but not with folate, choline, vitamin B12 concentrations, or with the studied polymorphisms. High methionine concentration in combination with high vitamin B2 or B6 concentrations was associated with lower occurrence of high-risk adenomas compared with these factors individually.CONCLUSIONS: High plasma concentrations of methionine and betaine, and vitamins B2 and B6 may reduce risk of developing colorectal adenomas.IMPACT: In addition to B-vitamins, methyl group donors such as methionine and betaine may play a role in colorectal carcinogenesis.
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| 2. |
- Gylling, Björn, 1978-, et al.
(författare)
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One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk
- 2019
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 144:5, s. 947-956
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Tidskriftsartikel (refereegranskat)abstract
- Background: One-carbon metabolism biomarker 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.Objective: 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.Design: 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 1211 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.Results: The ratio-based B-vitamin markers all outperformed tHcy as markers of total B-vitamin status, in both CRC cases and controls. Associations with CRC risk were similar for the ratio-based B-vitamin markers and total B-vitamin status (approximately 25% lower risk for high versus low B-vitamin status).Conclusions: Ratio-based B-vitamin markers were good predictors of total B-vitamin status, and displayed similar associations with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice to aid interpretation of tHcy results.
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| 3. |
- Midttun, Öivind, et al.
(författare)
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Plasma vitamin B-6 forms and their relation to transsulfuration metabolites in a large, population-based study
- 2007
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Ingår i: American Journal of Clinical Nutrition. - Bethesda : American society for nutrition. - 0002-9165 .- 1938-3207. ; 86:1, s. 131-138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vitamin B-6 exists in different forms; one of those forms, pyridoxal 5'-phosphate (PLP), serves a cofactor in many enzyme reactions, including the transsulfuration pathway, in which homocysteine is converted to cystathionine and then to cysteine. Data on the relations between indexes of vitamin B-6 status and transsulfuration metabolites in plasma are sparse and conflicting.Objective: We investigated the distribution and associations of various vitamin B-6 species in plasma and their relation to plasma concentrations of transsulfuration metabolites.Design: Nonfasting blood samples from 10 601 healthy subjects with a mean age of 56.4 y were analyzed for all known vitamin B-6 vitamers, folate, cobalamin, riboflavin, total homocysteine, cystathionine, total cysteine, methionine, and creatinine. All subjects were genotyped for the methylenetetrahydrofolate reductase (MTHFR) 677C -> T polymorphism.Results: Plasma concentrations of the main vitamin B-6 vitamers-PLP, pyridoxal, and 4-pyridoxic acid-were strongly correlated. Among the vitamin B-6 vitamers, PLP showed the strongest and most consistent inverse relation to total homocysteine and cystathionine, but the dose response was different for the 2 metabolites. The PLP-total homocysteine relation was significant only in the lowest quartile of the vitamin B-6 distribution and was strongest in subjects with the MTHFR 677TT genotype, whereas cystathionine showed a graded response throughout the range of vitamin B-6 vitamer concentrations, and the effect was not modified by the MTHFR 677C -> T genotype.Conclusion: This large population-based study provided precise estimates of the relation between plasma concentrations of vitamin B-6 forms and transsulfuration metabolites as modified by the MTHFR 677C -> T genotype.
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| 4. |
- Söderström, Elisabet, et al.
(författare)
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Plasma cotinine is positively associated with homocysteine in smokers but not in users of smokeless tobacco
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:21
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Tidskriftsartikel (refereegranskat)abstract
- Plasma total homocysteine (tHcy) is a risk marker, and smoking is an established risk factor for cardiovascular disease. It is unclear if the effect of smoked tobacco on homocysteine is mediated by nicotine or other combustion products in smoked tobacco. Snus (moist smokeless tobacco) is high nicotine-containing tobacco, and little is known about the effect of snus on plasma homocysteine. Therefore, we studied, in a cross-section of subjects (n = 1375) from the Northern Sweden Health and Disease Study, with strictly defined current smokers (n = 194) and snus users (n = 47), the impact of tobacco exposure on tHcy, assessed by self-reported tobacco habits and plasma cotinine concentrations. The snus users had higher cotinine concentrations than the smokers. Cotinine, creatinine, methylmalonic acid, and the methylenetetrahydrofolate reductase genotype (MTHFR) T allele were positively associated with tHcy among the smokers, but not among the snus users. No association was observed between tHcy and the number of cigarettes/day. There was a positive association between cotinine and tHcy in the smokers, but not among the snus users. This indicates that substances other than nicotine in tobacco smoke could be responsible for the differential effects on homocysteine status. Self-reported smoking should be complemented by a cotinine assay whenever possible.
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| 5. |
- Widbom, Lovisa, et al.
(författare)
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Elevated plasma cotinine is associated with an increased risk of developing IBD, especially among users of combusted tobacco
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science (PLOS). - 1932-6203. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Smoking has previously been associated with inflammatory bowel disease (IBD), but no study has reported on cotinine, an objective, biochemical measure of tobacco use. We aimed at testing the hypothesis that cotinine levels among healthy subjects are associated with an increased risk of developing IBD in later life.Design: We analysed plasma cotinine and evaluated corresponding lifestyle questionnaires that included tobacco habits in subjects (n = 96) who later developed late-onset IBD (70 ulcerative colitis (UC) and 26 Crohn’s disease (CD)) and in sex and age-matched controls (n = 191).Results: Patients who later developed IBD had significantly higher plasma cotinine levels compared to controls. In multivariable analysis, higher log-cotinine was associated with a higher risk of developing IBD (OR 1.34 (95% CI 1.01–1.63)). After stratifying for time to diagnosis, the association was only significant in subjects with shorter time (< 5.1 years) to diagnosis (OR 1.45 (1.09–1.92)). The findings were similar for UC- and CD-cases, but did not reach statistical significance in CD-cases. Although plasma cotinine concentrations were higher in snuff users compared to combusted tobacco users, no increase in the risk of IBD and lower risk of developing IBD among subjects with shorter time (< 5.1 years) to diagnosis was seen among snuff users.Conclusions: Cotinine, a biomarker of tobacco use, is associated with increased risk of developing late-onset IBD in general, and UC in particular. No increased risk among snuff users indicates that other components in combusted tobacco than nicotine may be involved in the pathogenesis of IBD among smokers.
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| 6. |
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