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Schneede, Jørn
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Publications (10 of 41) Show all publications
Park, J. Y., Bueno-de-Mesquita, H. B., Ferrari, P., Weiderpass, E., de Batlle, J., Tjonneland, A., . . . Slimani, N. (2019). Dietary folate intake and pancreatic cancer risk: Results from the European prospective investigation into cancer and nutrition. International Journal of Cancer, 144(7), 1511-1521
Open this publication in new window or tab >>Dietary folate intake and pancreatic cancer risk: Results from the European prospective investigation into cancer and nutrition
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 7, p. 1511-1521Article in journal (Refereed) Published
Abstract [en]

Pancreatic cancer (PC) has an exceptionally low survival rate and primary prevention strategies are limited. Folate plays an important role in one-carbon metabolism and has been associated with the risk of several cancers, but not consistently with PC risk. We aimed to investigate the association between dietary folate intake and PC risk, using the standardised folate database across 10 European countries. A total of 477,206 participants were followed up for 11 years, during which 865 incident primary PC cases were recorded. Folate intake was energy-adjusted using the residual method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. In multivariable analyses stratified by age, sex, study centre and adjusted for energy intake, smoking status, BMI, educational level, diabetes status, supplement use and dietary fibre intake, we found no significant association between folate intake and PC risk: the HR of PC risk for those in the highest quartile of folate intake (>= 353 mu g/day) compared to the lowest (<241 mu g/day) was 0.81 (95% CI: 0.51, 1.31; p(trend) = 0.38). In current smokers, a positive trend was observed in PC risk across folate quartiles [HR = 4.42 (95% CI: 1.05, 18.62) for >= 353 mu g/day vs. <241 mu g/day, p(trend) = 0.01]. Nonetheless, there was no significant interaction between smoking and dietary folate intake (p(interaction) = 0.99). We found no association between dietary folate intake and PC risk in this large European study.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
dietary folate intake, pancreatic cancer, EPIC study
National Category
Cancer and Oncology Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-162489 (URN)10.1002/ijc.31830 (DOI)000457773000004 ()30178496 (PubMedID)
Available from: 2019-08-26 Created: 2019-08-26 Last updated: 2019-08-26Bibliographically approved
Widbom, L., Schneede, J., Karling, P. & Hultdin, J. (2019). Higher plasma cotinine is associated with an increased risk for later developing IBD, especially among users of combusted tobacco. Journal of Crohn's & Colitis, 13, S508-S508
Open this publication in new window or tab >>Higher plasma cotinine is associated with an increased risk for later developing IBD, especially among users of combusted tobacco
2019 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 13, p. S508-S508Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2019
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-157520 (URN)10.1093/ecco-jcc/jjy222.898 (DOI)000460544503018 ()
Note

Supplement: 1

Available from: 2019-04-05 Created: 2019-04-05 Last updated: 2019-04-05Bibliographically approved
Sjölander, M., Lindholm, L., Pfister, B., Jonsson, J., Schneede, J., Lövheim, H. & Gustafsson, M. (2019). Impact of clinical pharmacist engagement in ward teams on the number of drug-related readmissions among Swedish older patients with dementia or cognitive impairment: an economic evaluation. Research in Social and Administrative Pharmacy, 5(3), 287-291
Open this publication in new window or tab >>Impact of clinical pharmacist engagement in ward teams on the number of drug-related readmissions among Swedish older patients with dementia or cognitive impairment: an economic evaluation
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2019 (English)In: Research in Social and Administrative Pharmacy, ISSN 1551-7411, E-ISSN 1934-8150, Vol. 5, no 3, p. 287-291Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Clinical pharmacists play an increasing role in the pharmacological treatment of hospital-admitted older patients with dementia or cognitive impairment. In an earlier randomised controlled trial, clinical pharmacist involvement in the ward team could significantly reduce drug-related readmissions in patient subgroups. However, the economic impact of the intervention has not been addressed so far.

OBJECTIVES: To evaluate the economic impact of clinical pharmacist engagement in hospital ward teams for medication therapy management in older patients with dementia or cognitive impairments.

METHODS: Economic evaluation of a randomised controlled trial conducted in two hospitals in Northern Sweden between January 2012 and December 2014. Participants included 460 hospital-admitted older patients with dementia or cognitive impairments. Patients were randomly assigned to usual care, or usual care with pharmacist intervention; the intervention consisted of medication reconciliation, medication review, and participation in ward rounds. The outcomes were measured as drug-related readmissions to hospital as assessed by a group of external experts, 180 and 30 days after discharge. Costs included pharmacists' direct labour costs for the interventions, average costs for drug-related readmissions, and from this the total cost per person was calculated.

RESULTS: The effect of the intervention on drug-related readmissions within 180 days was significant in patients without heart failure (subgroup analysis), and the intervention resulted in cost savings of €950 per person in this subgroup. Drug-related readmissions within 30 days were reduced in the total sample (post-hoc analysis), and the cost-savings in this intervention group were €460 per person.

CONCLUSIONS: Post-hoc and subgroup analyses indicate that engagement of pharmacists in hospital ward teams reduced the number of drug-related readmissions, and that the cost per person was lower in the intervention group compared to the control group. Including clinical pharmacists created savings in the subgroups of older patients with dementia or cognitive impairments.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Clinical pharmacy service, Dementia, Economic evaluation, Hospital readmissions, Randomised controlled trial
National Category
Social and Clinical Pharmacy Geriatrics Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-150414 (URN)10.1016/j.sapharm.2018.05.006 (DOI)000460091900007 ()29778344 (PubMedID)
Funder
Västerbotten County Council
Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2019-03-27Bibliographically approved
Gylling, B., Myte, R., Ulvik, A., Ueland, P. M., Midttun, Ø., Schneede, J., . . . Palmqvist, R. (2019). One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk. International Journal of Cancer, 144(5), 947-956
Open this publication in new window or tab >>One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 5, p. 68p. 947-956Article in journal (Other academic) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019. p. 68
Keywords
Biomarkers, colorectal cancer, metabolite ratios, B-vitamins, one-carbon metabolism
National Category
Clinical Laboratory Medicine
Research subject
Cancer Epidemiology
Identifiers
urn:nbn:se:umu:diva-142854 (URN)10.1002/ijc.31606 (DOI)000455041700003 ()29786139 (PubMedID)
Funder
Swedish Cancer Society, 12/501Swedish Cancer Society, 14/780
Note

Originally included in thesis in manuscript form

Available from: 2017-12-12 Created: 2017-12-12 Last updated: 2019-02-14Bibliographically approved
Gustafsson, M., Sjölander, M., Pfister, B., Schneede, J. & Lövheim, H. (2018). Effects of pharmacists' interventions on inappropriate drug use and drug-related readmissions in people with dementia: a secondary analysis of a randomized controlled trial. Pharmacy, 6(1), Article ID E7.
Open this publication in new window or tab >>Effects of pharmacists' interventions on inappropriate drug use and drug-related readmissions in people with dementia: a secondary analysis of a randomized controlled trial
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2018 (English)In: Pharmacy, ISSN 2226-4787, E-ISSN 1913-4711, Vol. 6, no 1, article id E7Article in journal (Refereed) Published
Abstract [en]

Age-associated physiological changes and extensive drug treatment including use of potentially inappropriate medications (PIMs) pose a significant risk of drug-drug interactions and adverse drug events among elderly people with dementia. This study aimed at analysing the effects of clinical pharmacists' interventions on use of PIMs, risk of emergency department visits, and time to institutionalization. Furthermore, a descriptive analysis was conducted of circumstances associated with drug-related readmissions. This is a secondary analysis of data from a randomized controlled intervention study conducted in two hospitals in Northern Sweden. The study included patients (n = 460) 65 years or older with dementia or cognitive impairment. The intervention consisted of comprehensive medication reviews conducted by clinical pharmacists as part of a healthcare team. There was a larger decrease in PIMs in the intervention group compared with the control group (p= 0.011). No significant difference was found in time to first all-cause emergency department visits (HR = 0.994, 95% CI = 0.755-1.307 p = 0.963, simple Cox regression) or time to institutionalization (HR = 0.761, 95% CI = 0.409-1.416 p = 0.389, simple Cox regression) within 180 days. Common reasons for drug-related readmissions were negative effects of sedatives, opioids, antidepressants, and anticholinergic agents, resulting in confusion, falling, and sedation. Drug-related readmissions were associated with living at home, heart failure, and diabetes. Pharmacist-provided interventions were able to reduce PIMs among elderly people with dementia and cognitive impairment.

Place, publisher, year, edition, pages
Basel: MDPI, 2018
Keywords
dementia, drug-related readmissions, medication reviews, potentially inappropriate medications
National Category
Pharmacology and Toxicology Geriatrics
Identifiers
urn:nbn:se:umu:diva-145404 (URN)10.3390/pharmacy6010007 (DOI)29337859 (PubMedID)
Available from: 2018-03-01 Created: 2018-03-01 Last updated: 2018-06-09Bibliographically approved
Holme, O., Loberg, M., Kalager, M., Bretthauer, M., Hernan, M. A., Aas, E., . . . Hoff, G. (2018). Long-Term Effectiveness of Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality in Women and Men A Randomized Trial. Annals of Internal Medicine, 168(11), 775-782
Open this publication in new window or tab >>Long-Term Effectiveness of Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality in Women and Men A Randomized Trial
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2018 (English)In: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 168, no 11, p. 775-782Article in journal (Refereed) Published
Abstract [en]

Background: The long-term effects of sigmoidoscopy screening on colorectal cancer (CRC) incidence and mortality in women and men are unclear.

Objective: To determine the effectiveness of flexible sigmoidoscopy screening after 15 years of follow-up in women and men.

Design: Randomized controlled trial. (ClinicalTrials.gov: NCT00119912)

Setting: Oslo and Telemark County, Norway. Participants: Adults aged 50 to 64 years at baseline without prior CRC.

Intervention: Screening (between 1999 and 2001) with flexible sigmoidoscopy with and without additional fecal blood testing versus no screening. Participants with positive screening results were offered colonoscopy.

Measurements: Age-adjusted CRC incidence and mortality stratified by sex.

Results: Of 98 678 persons, 20 552 were randomly assigned to screening and 78 126 to no screening. Adherence rates were 64.7% in women and 61.4% in men. Median follow-up was 14.8 years. The absolute risks for CRC in women were 1.86% in the screening group and 2.05% in the control group (risk difference, -0.19 percentage point [95% CI, -0.49 to 0.11 percentage point]; HR, 0.92 [CI, 0.79 to 1.07]). In men, the corresponding risks were 1.72% and 2.50%, respectively (risk difference, -0.78 percentage point [CI, -1.08 to -0.48 percentage points]; hazard ratio [HR], 0.66 [CI, 0.57 to 0.78]) (P for heterogeneity = 0.004). The absolute risks for death from CRC in women were 0.60% in the screening group and 0.59% in the control group (risk difference, 0.01 percentage point [CI, -0.16 to 0.18 percentage point]; HR, 1.01 [CI, 0.77 to 1.33]). The corresponding risks for death from CRC in men were 0.49% and 0.81%, respectively (risk difference, -0.33 percentage point [CI, -0.49 to -0.16 percentage point]; HR, 0.63 [CI, 0.47 to 0.83]) (P for heterogeneity = 0.014).

Limitation: Follow-up through national registries.

Conclusion: Offering sigmoidoscopy screening in Norway reduced CRC incidence and mortality in men but had little or no effect in women.

Place, publisher, year, edition, pages
American College of Physicians, 2018
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-150173 (URN)10.7326/M17-1441 (DOI)000434254100004 ()29710125 (PubMedID)
Funder
The Research Council of Norway
Available from: 2018-07-18 Created: 2018-07-18 Last updated: 2018-07-18Bibliographically approved
Myte, R., Gylling, B., Häggström, J., Schneede, J., Löfgren-Burström, A., Huyghe, J. R., . . . Van Guelpen, B. (2018). One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status. PLoS ONE, 13(4), Article ID e0196233.
Open this publication in new window or tab >>One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0196233Article in journal (Refereed) Published
Abstract [en]

Disturbances in one-carbon metabolism, intracellular reactions involved in nucleotide synthesis and methylation, likely increase the risk of colorectal cancer (CRC). However, results have been inconsistent. To explore whether this inconsistency could be explained by intertumoral heterogeneity, we evaluated a comprehensive panel of one-carbon metabolism biomarkers and some single nucleotide polymorphisms (SNPs) in relation to the risk of molecular subtypes of CRC defined by mutations in the KRAS and BRAF oncogenes. This nested case-control study included 488 CRC cases and 947 matched controls from two population-based cohorts in the Northern Sweden Health and Disease Study. We analyzed 14 biomarkers and 17 SNPs in prediagnostic blood and determined KRAS and BRAF mutation status in tumor tissue. In a multivariate network analysis, no variable displayed a strong association with the risk of specific CRC subtypes. A non-synonymous SNP in the CTH gene, rs1021737, had a stronger association compared with other variables. In subsequent univariate analyses, participants with variant rs1021737 genotype had a decreased risk of KRAS-mutated CRC (OR per allele = 0.72, 95% CI = 0.50, 1.05), and an increased risk of BRAF-mutated CRC (OR per allele = 1.56, 95% CI = 1.07, 2.30), with weak evidence for heterogeneity (Pheterogeneity = 0.01). This subtype-specific SNP association was not replicated in a case-case analysis of 533 CRC cases from The Cancer Genome Atlas (P = 0.85). In conclusion, we found no support for clear subtype-specific roles of one-carbon metabolism biomarkers and SNPs in CRC development, making differences in CRC molecular subtype distributions an unlikely explanation for the varying results on the role of one-carbon metabolism in CRC development across previous studies. Further investigation of the CTH gene in colorectal carcinogenesis with regards to KRAS and BRAF mutations or other molecular characteristics of the tumor may be warranted.

Place, publisher, year, edition, pages
Public Library of Science, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-147822 (URN)10.1371/journal.pone.0196233 (DOI)000430802400077 ()29694444 (PubMedID)
Available from: 2018-05-21 Created: 2018-05-21 Last updated: 2019-05-24Bibliographically approved
Sandqvist, A., Schneede, J., Kylhammar, D., Henrohn, D., Lundgren, J., Hedeland, M., . . . Wikström, G. (2018). Plasma l-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction. Heart and Vessels, 33(3), 255-263
Open this publication in new window or tab >>Plasma l-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction
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2018 (English)In: Heart and Vessels, ISSN 0910-8327, E-ISSN 1615-2573, Vol. 33, no 3, p. 255-263Article in journal (Refereed) Published
Abstract [en]

Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from L-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, L-arginine, L-ornithine, and L-citrulline were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma levels of ADMA and SDMA were higher, whereas L-arginine and L-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p < 0.001). Patients with PAH also had lower levels of L-arginine than patients with LVSD (p < 0.05). L-Arginine correlated to 6 min walking distance (6MWD) (r s = 0.58, p = 0.006) and L-arginine/ADMA correlated to WHO functional class (r s = -0.46, p = 0.043) in PAH. In conclusion, L-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, L-arginine correlated with 6MWD in PAH. L-arginine may provide useful information in differentiating PAH from LVSD.

Keywords
Dimethylarginines, L-Arginine, Left heart failure, Pulmonary arterial hypertension, Systolic dysfunction
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-140337 (URN)10.1007/s00380-017-1055-7 (DOI)000426278900005 ()28975394 (PubMedID)2-s2.0-85030313830 (Scopus ID)
Available from: 2017-10-05 Created: 2017-10-05 Last updated: 2018-06-09Bibliographically approved
Gustafsson, M., Sjölander, M., Pfister, B., Jonsson, J., Schneede, J. & Lövheim, H. (2017). Pharmacist participation in hospital ward teams and hospital readmission rates among people with dementia: a randomized controlled trial. European Journal of Clinical Pharmacology, 7(73), 827-835
Open this publication in new window or tab >>Pharmacist participation in hospital ward teams and hospital readmission rates among people with dementia: a randomized controlled trial
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2017 (English)In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 7, no 73, p. 827-835Article in journal (Refereed) Published
Abstract [en]

Purpose: To assess whether comprehensive medication reviews conducted by clinical pharmacists as part of a healthcare team reduce drug-related hospital readmission rates among people with dementia or cognitive impairment.

Methods: This randomized controlled trial was carried out between January 9, 2012, and December 2, 2014. Patients aged ≥65 years with dementia or cognitive impairment admitted to three wards at two hospitals located in Northern Sweden were included.

Results: Of the 473 deemed eligible for participation, 230 were randomized to intervention and 230 to control group by block randomization. The primary outcome, risk of drug-related hospital readmissions, was assessed at 180 days of follow-up by intention-to-treat analysis.

During the 180 days of follow-up, 18.9% (40/212) of patients in the intervention group and 23.0% (50/217) of those in the control group were readmitted for drug-related reasons (HR = 0.80, 95% CI = 0.53–1.21, p = 0.28, univariable Cox regression). Heart failure was significantly more common in the intervention group. After adjustment for heart failure as a potential confounder and an interaction term, multiple Cox regression analysis indicated that pharmacist participation significantly reduced the risk of drug-related readmissions (HR = 0.49, 95% CI = 0.27–0.90, p = 0.02). A post-hoc analysis showed a significantly reduced risk of 30-day readmissions due to drug-related problems in the total sample (without adjustment for heart failure).

Conclusion: Participation of clinical pharmacists in healthcare team conducting comprehensive medication reviews did not significantly reduce the risk of drug-related readmissions in patients with dementia or cognitive impairment; however, post-hoc and subgroup analyses indicated significant effects favoring the intervention. More research is needed.

Trial registration: Clinical trials NCT01504672.

Place, publisher, year, edition, pages
Springer, 2017
Keywords
Medication reviews, Clinical pharmacists, Drug-related readmissions, Dementia, Old people
National Category
Geriatrics Social and Clinical Pharmacy
Identifiers
urn:nbn:se:umu:diva-118307 (URN)10.1007/s00228-017-2249-8 (DOI)000405666100005 ()
Available from: 2016-03-15 Created: 2016-03-15 Last updated: 2018-06-07Bibliographically approved
Myte, R., Gylling, B., Häggström, J., Schneede, J., Ueland, P. M., Hallmans, G., . . . Van Guelpen, B. (2017). Untangling the role of one-carbon metabolism in colorectal cancer risk: a comprehensive Bayesian network analysis. Scientific Reports, 7, Article ID 43434.
Open this publication in new window or tab >>Untangling the role of one-carbon metabolism in colorectal cancer risk: a comprehensive Bayesian network analysis
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 43434Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:umu:diva-132798 (URN)10.1038/srep43434 (DOI)000395240100001 ()28233834 (PubMedID)
Available from: 2017-05-11 Created: 2017-05-11 Last updated: 2019-05-24Bibliographically approved
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