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ABCC2 transporter gene polymorphisms, diet and risk of colorectal cancer: a Danish prospective cohort study.

https://arctichealth.org/en/permalink/ahliterature126046
Source
Scand J Gastroenterol. 2012 May;47(5):572-4
Publication Type
Article
Date
May-2012

Associations between common polymorphisms in CYP2R1 and GC, Vitamin D intake and risk of colorectal cancer in a prospective case-cohort study in Danes.

https://arctichealth.org/en/permalink/ahliterature307070
Source
PLoS One. 2020; 15(2):e0228635
Publication Type
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Date
2020
Author
Tine Iskov Kopp
Ulla Vogel
Vibeke Andersen
Author Affiliation
Danish Cancer Society Research Center, Copenhagen, Denmark.
Source
PLoS One. 2020; 15(2):e0228635
Date
2020
Language
English
Publication Type
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Keywords
Cholestanetriol 26-Monooxygenase - genetics
Colorectal Neoplasms - blood - genetics
Cytochrome P450 Family 2 - genetics
Denmark
Dietary Supplements
Female
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Vitamin D - administration & dosage - blood
Vitamin D-Binding Protein - genetics
Abstract
The association between vitamin D and incidence of colorectal cancer has been thoroughly investigated, but the results are conflicting. The objectives in this study were to investigate whether two functional polymorphisms in GC and CYP2R1, respectively, previously shown to predict vitamin D concentrations, were associated with risk of colorectal cancer; and further, to assess gene-environment interaction between the polymorphisms and intake of vitamin D through diet and supplementation in relation to risk of colorectal cancer.
A nested case-cohort study of 920 colorectal cancer cases and 1743 randomly selected participants from the Danish prospective "Diet, Cancer and Health" study was performed. Genotypes CYP2R1/rs10741657 and GC/rs4588 were determined by PCR-based KASP™ genotyping assay. Vitamin D intake from supplements and diet was assessed from a validated food frequency questionnaire. Incidence rate ratios were estimated by the Cox proportional hazards model, and interactions between polymorphisms in GC and CYP2R1 and vitamin D intake in relation to risk of colorectal cancer were assessed.
Neither of the two polymorphisms was associated with risk of colorectal cancer per se. Heterozygote carriage of CYP2R1/rs10741657 and GC/rs4588, and carriage of two risk alleles (estimated by a genetic risk score) were weakly associated with 9-12% decreased risk of colorectal cancer per 3 µg intake of vitamin D per day (IRRCYP2R1/rs10741657 = 0.88, 95% CI: 0.79-0.97; IRRGC/rs4588 = 0.91, 95% CI: 0.82-1.01, IRRGRS2 = 0.90, 95% CI: 0.81-0.99).
The results suggest that genetic variation in vitamin D metabolising genes may influence the association between vitamin D intake, through food and supplementation, and risk of colorectal cancer.
NCT03370432. Registered 12 December 2017 (retrospectively registered).
PubMed ID
32012190 View in PubMed
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Common polymorphisms in the microsomal epoxide hydrolase and N-acetyltransferase 2 genes in association with inflammatory bowel disease in the Danish population.

https://arctichealth.org/en/permalink/ahliterature137943
Source
Eur J Gastroenterol Hepatol. 2011 Mar;23(3):269-74
Publication Type
Article
Date
Mar-2011
Author
Anja Ernst
Vibeke Andersen
Mette Ostergaard
Bent A Jacobsen
Inge S Pedersen
Asbjørn M Drewes
Henrik Okkels
Henrik B Krarup
Author Affiliation
Department of Clinical Biochemistry, Section of Molecular Diagnostics, Aalborg Hospital, Aarhus University Hospital, Reberbansgade, Denmark. ae@rn.dk
Source
Eur J Gastroenterol Hepatol. 2011 Mar;23(3):269-74
Date
Mar-2011
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Arylamine N-Acetyltransferase - genetics
Azathioprine - therapeutic use
Chronic Disease
Cohort Studies
Denmark - epidemiology
Epoxide Hydrolases - genetics
Female
Genetic Predisposition to Disease
Humans
Inflammatory Bowel Diseases - drug therapy - enzymology - epidemiology - genetics
Male
Microsomes - enzymology
Middle Aged
Polymorphism, Genetic
Prevalence
Risk factors
Young Adult
Abstract
Chronic inflammatory bowel disease (IBD) is characterized by recurrent inflammation of the intestinal mucosa. Reactive molecules play a central role in altering the intestinal permeability, which may induce or sustain an immune response. Changes in detoxification of substances that causes epithelial damage may confer susceptibility to IBD. Hence, polymorphic enzymes involved in the detoxification processes may be risk factors of IBD.
The two biotransformation enzymes microsomal epoxide hydrolase and N-acetyltransferase 2 were genotyped using TaqMan based real-time PCR in 388 patients with Crohn's disease, 565 patients with ulcerative colitis and 796 healthy controls.
No association was found between the genotypes of low microsomal epoxide hydrolase activity or slow N-acetyltransferase 2 acetylator status and IBD. An association was found between microsomal epoxide hydrolase and less than 40 years of age at diagnosis of Crohn's disease and microsomal epoxide hydrolase and azathiporine use in patients with ulcerative colitis. No other evident phenotypic associations were found for the two enzymes and either ulcerative colitis or Crohn's disease. A possible modification of smoking on microsomal epoxide hydrolase genotypes was found.
Microsomal epoxide hydrolase and N-acetyltransferase 2 genotypes appear not to be individual risk factors of IBD, or to be important in relation to phenotypic characteristics of IBD.
PubMed ID
21228703 View in PubMed
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Cyclooxygenase-2 (COX-2) polymorphisms and risk of inflammatory bowel disease in a Scottish and Danish case-control study.

https://arctichealth.org/en/permalink/ahliterature141181
Source
Inflamm Bowel Dis. 2011 Apr;17(4):937-46
Publication Type
Article
Date
Apr-2011
Author
Vibeke Andersen
Elaine Nimmo
Henrik B Krarup
Hazel Drummond
Jane Christensen
Gwo-Tzer Ho
Mette Ostergaard
Anja Ernst
Charlie Lees
Bent A Jacobsen
Jack Satsangi
Ulla Vogel
Author Affiliation
Medical Department, Viborg Regional Hospital, Viborg, Denmark. va9791@gmail.com
Source
Inflamm Bowel Dis. 2011 Apr;17(4):937-46
Date
Apr-2011
Language
English
Publication Type
Article
Keywords
Adult
Aged
Biological Markers - metabolism
Case-Control Studies
Colitis, Ulcerative - genetics
Crohn Disease - genetics
Cyclooxygenase 2 - genetics
DNA - genetics
Denmark
Female
Gene Frequency
Genotype
Humans
Male
Middle Aged
Polymerase Chain Reaction
Polymorphism, Genetic - genetics
Scotland
Young Adult
Abstract
Inflammatory bowel diseases (IBDs) are a result of interactions between luminal pathogens and the intestinal immune response. Cyclooxygenase-2 (COX-2) plays a key role in the regulation of the inflammatory response upon stimulation by luminal pathogens via Toll-like receptors.
Genotypes of the COX-2/PTGS2/PGHS2 A-1195G (rs689466), G-765C (rs20417), and T8473C (rs5275) polymorphisms were assessed in a Scottish and Danish case-control study including 732 Crohn's disease (CD) cases, 973 ulcerative colitis (UC) cases, and 1157 healthy controls using logistic regression.
Carriers of the COX-2 A-1195G variant allele had increased risk of UC (odds ratio [OR], 95% confidence interval [CI] = 1.25 [1.02-1.54], P = 0.03) and of both UC and IBD among never smokers (OR [95% CI] = 1.47 [1.11-1.96], P = 0.01 and OR [95% CI] = 1.37 [1.06-1.77], P = 0.02, respectively). Furthermore, this variant genotype was associated with increased risk of diagnosis of UC before age 40 years and with extensive UC (OR [95% CI] = 1.34 [1.11-1.62], P = 0.002 and OR [95% CI] = 1.32 [1.03-1.69], P = 0.03, respectively).
COX-2 A-1195G polymorphism was associated with the risk of UC, especially among never-smokers, suggesting that low activity of COX-2 may predispose to UC. Our results suggest that inclusion of smoking status may be essential for the evaluation of the role of genetic predisposition to IBD.
PubMed ID
20803508 View in PubMed
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Danish cohort of monozygotic inflammatory bowel disease twins: Clinical characteristics and inflammatory activity.

https://arctichealth.org/en/permalink/ahliterature281741
Source
World J Gastroenterol. 2016 Jun 07;22(21):5050-9
Publication Type
Article
Date
Jun-07-2016
Author
Frederik Trier Moller
Lina Knudsen
Marcus Harbord
Jack Satsangi
Hannah Gordon
Lene Christiansen
Kaare Christensen
Tine Jess
Vibeke Andersen
Source
World J Gastroenterol. 2016 Jun 07;22(21):5050-9
Date
Jun-07-2016
Language
English
Publication Type
Article
Keywords
Adult
Aged
Anti-Inflammatory Agents - therapeutic use
Biomarkers - analysis
Biopsy
Case-Control Studies
Cohort Studies
Colectomy
Colitis, Ulcerative - diagnosis - genetics - metabolism - therapy
Crohn Disease - diagnosis - genetics - metabolism - therapy
Denmark
Diseases in Twins - diagnosis - genetics - metabolism - therapy
Endoscopy, Gastrointestinal
Female
Gastrointestinal Agents - therapeutic use
Humans
Immunosuppressive Agents - therapeutic use
Leukocyte L1 Antigen Complex - analysis
Male
Middle Aged
Phenotype
Registries
Severity of Illness Index
Twins, Monozygotic - genetics
Up-Regulation
Abstract
To describe the establishment of a Danish inflammatory bowel diseases (IBD) twin cohort with focus on concordance of treatment and inflammatory markers.
We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the -80 °C mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria.
We identified 159 MZ IBD twin pairs, in a total of 62 (39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU (IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 µg/g in 2 participants, and above 50 µg/g in a further 5 participants.
The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins.
Notes
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PubMed ID
27275097 View in PubMed
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Effectiveness of anti-tumour necrosis factor-a therapy in Danish patients with inflammatory bowel diseases.

https://arctichealth.org/en/permalink/ahliterature268292
Source
Dan Med J. 2015 Mar;62(3)
Publication Type
Article
Date
Mar-2015
Author
Steffen Bank
Paal Skytt Andersen
Johan Burisch
Natalia Pedersen
Stine Roug
Julie Galsgaard
Stine Ydegaard Turino
Jacob Broder Brodersen
Shaista Rashid
Sara Avlund
Thomas Bastholm Olesen
Anders Green
Hans Jürgen Hoffmann
Marianne Kragh Thomsen
Vibeke Østergaard Thomsen
Bjørn Andersen Nexø
Ulla Vogel
Vibeke Andersen
Source
Dan Med J. 2015 Mar;62(3)
Date
Mar-2015
Language
English
Publication Type
Article
Keywords
Adalimumab - therapeutic use
Adolescent
Adult
Age Factors
Aged
Anti-Inflammatory Agents - therapeutic use
Child
Cohort Studies
Colitis, Ulcerative - drug therapy
Crohn Disease - drug therapy
Denmark
Female
Humans
Infliximab - therapeutic use
Male
Middle Aged
Odds Ratio
Registries
Retrospective Studies
Smoking - adverse effects
Treatment Outcome
Tumor Necrosis Factor-alpha - antagonists & inhibitors
Young Adult
Abstract
The objective of this study was to evaluate the outcome of anti-tumour necrosis factor-a (anti-TNF) treatment in a large cohort of patients with inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC) in clinical practice and to establish a cohort for future studies of genetic markers associated with treatment response.
A national, clinically based cohort of previously naïve anti-TNF treated patients from 18 medical departments was established. The patients were screened for tuberculosis prior to treatment initiation. By combining the unique personal identification number of Danish citizens (the CPR number) from blood samples with data from the National Patient Registry, patients with International Classification of Diseases, Version 10 (ICD-10) codes K50-K63 were identified. Treatment efficacy reflected the maximum response within 22 weeks.
Among 492 patients with CD and 267 patients with UC, 74%/13%/14% and 65%/12%/24% were responders, partial responders and non-responders to anti-TNF therapy, respectively. More patients with UC than with CD were non-responders (odds ratio (OR) = 1.96, 95% confidence interval (CI): 1.34-2.87, p = 0.001). Young age was associated with a beneficial response (p = 0.03), whereas smoking = 10 cigarettes/day was associated with non-response among patients with CD (OR = 2.33, 95% CI: 1.13-4.81, p = 0.03).
In this clinically based cohort of Danish patients with IBD treated with anti-TNF, high response rates were found. Heavy smoking was associated with non-response, whereas young age at treatment initiation was associated with a beneficial response among patients with CD. Thus, the results obtained in this cohort recruited from clinical practice were similar to those previously obtained in clinical trials.
The work was funded by Health Research Fund of Central Denmark Region, Colitis-Crohn Foreningen and the University of Aarhus (PhD grant).
Clinicaltrials NCT02322008.
PubMed ID
25748864 View in PubMed
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Exposure to the Danish Mandatory Vitamin D Fortification Policy in Prenatal Life and the Risk of Developing Coeliac Disease-The Importance of Season: A Semi Ecological Study.

https://arctichealth.org/en/permalink/ahliterature306092
Source
Nutrients. 2020 Apr 27; 12(5):
Publication Type
Journal Article
Date
Apr-27-2020
Author
Caroline Moos
Katrine S Duus
Peder Frederiksen
Berit L Heitmann
Vibeke Andersen
Author Affiliation
Focused Research Unit for Molecular Diagnostic and Clinical Research, Institute of Regional Health Research, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark.
Source
Nutrients. 2020 Apr 27; 12(5):
Date
Apr-27-2020
Language
English
Publication Type
Journal Article
Keywords
Celiac Disease - epidemiology - etiology - prevention & control
Denmark - epidemiology
Diet - adverse effects
Dietary Supplements
Female
Follow-Up Studies
Food, Fortified - adverse effects - standards
Humans
Male
Margarine - adverse effects - standards
Nutrition Policy
Nutritional Requirements
Pregnancy
Prenatal Exposure Delayed Effects
Seasons
Vitamin D - administration & dosage - adverse effects
Abstract
Few studies have examined the role of maternal diet in relation to development of coeliac disease (CD). In Denmark, cancellation of mandatory vitamin D fortification of margarine in June 1985 provided this opportunity. This study examined if season of birth or prenatal exposure to extra vitamin D from food fortification were associated with developing CD later in life. A strength of this study is the distinctly longer follow-up of patients (30 years). This register-based study has a semi-ecological design. Logistic regression analysis was used to estimate odds ratios and to calculate 95% confidence intervals. The odds ratio for developing CD was 0.81 (95% CI 0.66; 1.00 p = 0.054), comparing those with fetal exposure to mandatory vitamin D fortification policy of margarine to those without after adjusting for gender and season of birth. There was a statistically significant season effect particularly for children born in autumn (OR 1.6 95% CI 1.16; 2.21) and born in summer (OR 1.5 95% CI 1.1; 2.1) when compared to children born in winter. Although this study did not find evidence to support the premise that prenatal exposure to small extra amounts of vitamin D from a mandatory food fortification policy lowered risk of developing CD, the small number of CD cases and observed association between season of birth and CD suggest that environmental exposure ought to be further explored.
PubMed ID
32349457 View in PubMed
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Familial risk of inflammatory bowel disease: a population-based cohort study 1977-2011.

https://arctichealth.org/en/permalink/ahliterature263746
Source
Am J Gastroenterol. 2015 Apr;110(4):564-71
Publication Type
Article
Date
Apr-2015
Author
Frederik Trier Moller
Vibeke Andersen
Jan Wohlfahrt
Tine Jess
Source
Am J Gastroenterol. 2015 Apr;110(4):564-71
Date
Apr-2015
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Age Factors
Aged
Cohort Studies
Colitis, Ulcerative - epidemiology - genetics
Confounding Factors (Epidemiology)
Crohn Disease - epidemiology - genetics
Denmark - epidemiology
Family
Female
Humans
Incidence
Inflammatory Bowel Diseases - epidemiology - genetics
Male
Middle Aged
Odds Ratio
Poisson Distribution
Registries
Research Design
Retrospective Studies
Risk assessment
Risk factors
Sensitivity and specificity
Abstract
Estimates of familial risk of inflammatory bowel diseases (IBDs), Crohn's disease (CD), and ulcerative colitis (UC) are needed for counseling of patients and could be used to target future prevention. We aimed to provide comprehensive population-based estimates of familial risk of IBD.
The study encompassed the entire Danish population during 1977-2011 (N=8,295,773; 200 million person-years). From national registries, we obtained information on diagnosis date of IBD (N=45,780) and family ties. Using Poisson regression, we estimated incidence rate ratios (IRRs) of IBD in relatives of IBD cases compared with individuals with relatives of the same type without IBD.
The risk of CD was significantly increased in first-degree (IRR, 7.77; 95% confidence interval (CI), 7.05-8.56), second-degree (IRR, 2.44; 95% CI, 2.01-2.96), and third-degree relatives (IRR, 1.88; 95% CI, 1.30-2.71) to patients with CD, and was less pronounced in relatives to UC cases. Likewise, the risk of UC was increased in first-degree (IRR, 4.08; 95% CI, 3.81-4.38), second-degree (IRR, 1.85; 95% CI, 1.60-2.13), and third-degree relatives (IRR, 1.51; 95% CI, 1.07-2.12) of UC cases, and less pronounced in relatives of CD cases. IRRs increased with two or more IBD-affected relatives and were modified by age, with the highest family-related IRR observed in early life.
The risk of IBD is significantly increased in first -, second-, and third-degree relatives of IBD-affected cases, with up to 12% of all IBD cases being family cases. The risk is particularly pronounced in young individuals.
PubMed ID
25803400 View in PubMed
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Genetic variants of glutathione S-transferases mu, theta, and pi display no susceptibility to inflammatory bowel disease in the Danish population.

https://arctichealth.org/en/permalink/ahliterature143646
Source
Scand J Gastroenterol. 2010 Sep;45(9):1068-75
Publication Type
Article
Date
Sep-2010
Author
Anja Ernst
Vibeke Andersen
Mette Østergaard
Bent A Jacobsen
Enrika Dagiliene
Inge S Pedersen
Asbjørn M Drewes
Henrik Okkels
Henrik B Krarup
Author Affiliation
Department of Clinical Biochemistry, Section of Molecular Diagnostics, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. ae@rn.dk
Source
Scand J Gastroenterol. 2010 Sep;45(9):1068-75
Date
Sep-2010
Language
English
Publication Type
Article
Keywords
Adult
Colitis, Ulcerative - genetics
Crohn Disease - genetics
Denmark
Female
Genetic Predisposition to Disease
Genotype
Glutathione S-Transferase pi - genetics
Glutathione Transferase - genetics
Humans
Inflammatory Bowel Diseases - genetics
Male
Middle Aged
Smoking - adverse effects
Abstract
A combination of genetic predisposition and interactions with environmental factors are believed to be responsible for disease phenotype and disease progression in inflammatory bowel diseases. The harmful effect of smoking and other environmental factors is believed to be highly dependent on the activity of detoxification enzymes. The aims of the study were to examine possible associations between the detoxifying glutathione S-transferases (GSTs) family mu, theta and pi gene variants and inflammatory bowel disease, and secondly to examine a potential genotype-genotype interaction between these variants. Genotype-disease phenotype associations and a possible interaction between genotype and cigarette smoking were also assessed.
Three hundred and eighty-eight patients with Crohn's disease (CD), 565 patients with ulcerative colitis (UC) and 796 healthy Danish controls were included in the study. Genomic DNA was used for genotyping of the GST genes using PCR or real-time PCR.
No associations were found between GST genotypes and inflammatory bowel diseases. Neither did a combination of the GST genotypes reveal any associations. No genotype-disease phenotype associations were found. Smoking was positively associated with CD and negatively associated with UC. An interaction between smoking and GSTM1*0 genotype was found for UC, where the GSTM1*0 genotype appear to strengthen the protective effect of smoking on disease susceptibility.
The GST genotypes do not seem to be important in susceptibility of inflammatory bowel disease in the Danish population. Nor did we find convincing evidence of associations between GST genotype and phenotypic features of inflammatory bowel diseases.
PubMed ID
20459366 View in PubMed
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Heme oxygenase-1 polymorphism is not associated with risk of colorectal cancer: a Danish prospective study.

https://arctichealth.org/en/permalink/ahliterature138322
Source
Eur J Gastroenterol Hepatol. 2011 Mar;23(3):282-5
Publication Type
Article
Date
Mar-2011
Author
Vibeke Andersen
Jane Christensen
Kim Overvad
Anne Tjønneland
Ulla Vogel
Author Affiliation
Medical Department, Viborg Regional Hospital, Denmark. vibeke.andersen@viborg.rm.dk
Source
Eur J Gastroenterol Hepatol. 2011 Mar;23(3):282-5
Date
Mar-2011
Language
English
Publication Type
Article
Keywords
Case-Control Studies
Colorectal Neoplasms - epidemiology - genetics
Denmark - epidemiology
Female
Food Habits
Heme - metabolism
Heme Oxygenase-1 - genetics
Humans
Male
Meat - adverse effects - statistics & numerical data
Middle Aged
Polymorphism, Genetic
Prospective Studies
Risk
Abstract
Intake of red and processed meat confers risk of colorectal cancer (CRC). We wanted to test whether heme in meat promotes carcinogenesis.
Heme oxygenase-1 (HO-1, HMOX1) A-413T (rs2071746) was assessed in a nested case-cohort study of 383 CRC cases and 763 randomly selected participants from a prospective study of 57 053 individuals. Incidence rate ratios and 95% confidence intervals were calculated.
No association was found between the HO-1 polymorphism and CRC (P value for trend for the fully adjusted estimates = 0.29). No interaction with meat intake was found (P value for interaction = 0.55).
The studied HO-1 polymorphism was not associated with risk of CRC suggesting that heme from meat is not important in CRC development.
PubMed ID
21191307 View in PubMed
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18 records – page 1 of 2.