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Association between tumor necrosis factor-a antagonists and risk of cancer in patients with inflammatory bowel disease.

https://arctichealth.org/en/permalink/ahliterature104168
Source
JAMA. 2014 Jun 18;311(23):2406-13
Publication Type
Article
Date
Jun-18-2014
Author
Nynne Nyboe Andersen
Björn Pasternak
Saima Basit
Mikael Andersson
Henrik Svanström
Sarah Caspersen
Pia Munkholm
Anders Hviid
Tine Jess
Author Affiliation
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Source
JAMA. 2014 Jun 18;311(23):2406-13
Date
Jun-18-2014
Language
English
Publication Type
Article
Keywords
Adult
Cohort Studies
Denmark
Female
Humans
Inflammatory Bowel Diseases - drug therapy
Male
Middle Aged
Neoplasms - epidemiology
Registries
Risk
Risk factors
Tumor Necrosis Factor-alpha - antagonists & inhibitors
Young Adult
Abstract
A Cochrane review and network meta-analysis concluded that there is need for more research on adverse effects, including cancer, after treatment with tumor necrosis factor a (TNF-a) antagonists and that national registries and large databases would provide relevant sources of data to evaluate these effects.
To investigate whether patients with inflammatory bowel disease (IBD) exposed to TNF-a antagonists were at increased risk of developing cancer.
Nationwide register-based cohort study in Denmark, 1999-2012. Participants were 56,146 patients 15 years or older with IBD identified in the National Patient Registry, of whom 4553 (8.1%) were exposed to TNF-a antagonists. Cancer cases were identified in the Danish Cancer Registry.
Rate ratios (RRs) for incident cancer (overall and site-specific) comparing TNF-a antagonist users and nonusers, estimated using Poisson regression adjusted for age, calendar year, disease duration, propensity scores, and use of other IBD medications.
During 489,433 person-years of follow-up (median, 9.3 years [interquartile range, 4.2-14.0]), 81 of 4553 patients exposed to TNF-a antagonists (1.8%) (median follow-up, 3.7 years [interquartile range, 1.8-6.0]) and 3465 of 51,593 unexposed patients (6.7%) developed cancer, yielding a fully adjusted RR of 1.07 (95% CI, 0.85-1.36). There was no significantly increased risk of cancer in analyses according to time since first TNF-a antagonist exposure (less than 1 year: RR, 1.10 [95% CI, 0.67-1.81]; 1 to less than 2 years: RR, 1.22 [95% CI, 0.77-1.93]; 2 to less than 5 years: RR, 0.82 [95% CI, 0.54-1.24]; 5 or more years: RR, 1.33 [95% CI, 0.88-2.03]) and in analyses according to the number of TNF-a antagonist doses received (1 to 3 doses: RR, 1.02 [95% CI, 0.71-1.47]; 4 to 7 doses: RR, 0.89 [95% CI, 0.55-1.42]; 8 or more doses: RR, 1.29 [95% CI, 0.90-1.85]). No site-specific cancers were in significant excess in fully adjusted models.
In this Danish nationwide study, exposure to TNF-a antagonists among patients with IBD was not associated with an increased risk of cancer over a median follow-up of 3.7 years among those exposed. An increased risk associated with longer-term accumulated doses and follow-up cannot be excluded.
PubMed ID
24938563 View in PubMed
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Body mass index and risk of autoimmune diseases: a study within the Danish National Birth Cohort.

https://arctichealth.org/en/permalink/ahliterature260519
Source
Int J Epidemiol. 2014 Jun;43(3):843-55
Publication Type
Article
Date
Jun-2014
Author
Maria C Harpsøe
Saima Basit
Mikael Andersson
Nete M Nielsen
Morten Frisch
Jan Wohlfahrt
Ellen A Nohr
Allan Linneberg
Tine Jess
Source
Int J Epidemiol. 2014 Jun;43(3):843-55
Date
Jun-2014
Language
English
Publication Type
Article
Keywords
Adult
Autoimmune Diseases - epidemiology
Body mass index
Cohort Studies
Denmark - epidemiology
Female
Health Behavior
Humans
Incidence
Longitudinal Studies
Obesity - epidemiology
Risk factors
Socioeconomic Factors
Abstract
A possible aetiological link between obesity and certain autoimmune diseases (ADs) has been suggested. We investigated the associations between body mass index (BMI, kg/m2) and 43 ADs.
75,008 women participating in the Danish National Birth Cohort were followed during a median time of 11 years. Diagnoses on ADs were retrieved from the Danish National Patient Register. Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated adjusting for potential confounders (smoking, alcohol, parity and socio-occupational status).
During follow-up, 2430 women (3.2%) developed a total of 2607 new-onset ADs. Risk of any autoimmune disease was increased in obese women (HR, 1.27; 95% CI, 1.11 to 1.46) compared with normal weight women (18.5-=25 kg/m2). Obese women (BMI=30 kg/m2) were at increased risk of sarcoidosis (HR 3.59; 95% CI, 2.31 to 5.57) and type 1 diabetes mellitus (HR 2.67; 95% CI, 1.71 to 4.17). Risk of dermatitis herpetiformis increased by 14% (95% CI, 1% to 30%) per BMI unit. Conversely, risk of celiac disease and Raynaud's phenomenon decreased by 7% (95% CI, 1% to 13%) and 12% (95% CI, 4% to 19%) per BMI unit, respectively. Further associations between BMI and risk of psoriasis, rheumatoid arthritis and Crohn's disease were suggested.
BMI was found to be associated with several Ads. This was most pronounced between obesity and risk of sarcoidosis and and risk of type 1 diabetes mellitus. These novel findings need confirmation and the possible role of adipose tissue-derived immunological changes in the development of autoimmune reactions needs consideration.
PubMed ID
24609069 View in PubMed
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Body Mass Index and Risk of Infections Among Women in the Danish National Birth Cohort.

https://arctichealth.org/en/permalink/ahliterature283057
Source
Am J Epidemiol. 2016 Jun 01;183(11):1008-17
Publication Type
Article
Date
Jun-01-2016
Author
Maria C Harpsøe
Nete M Nielsen
Nina Friis-Møller
Mikael Andersson
Jan Wohlfahrt
Allan Linneberg
Ellen A Nohr
Tine Jess
Source
Am J Epidemiol. 2016 Jun 01;183(11):1008-17
Date
Jun-01-2016
Language
English
Publication Type
Article
Keywords
Acute Disease
Adult
Anti-Infective Agents - therapeutic use
Body Height
Body mass index
Body Weight
Communicable Diseases - drug therapy - epidemiology
Denmark - epidemiology
Female
Health Behavior
Humans
Incidence
Obesity - epidemiology
Overweight - epidemiology
Proportional Hazards Models
Prospective Studies
Respiratory Tract Infections - epidemiology
Risk factors
Skin Diseases, Infectious - epidemiology
Socioeconomic Factors
Thinness - epidemiology
Abstract
We investigated the possible association between body mass index (BMI; weight (kg)/height (m)(2)) and hospitalization or treatment for acute infection in a prospective cohort study. We linked 75,001 women enrolled in the Danish National Birth Cohort from 1996 to 2002, who had information on BMI and a broad range of confounders, to data on infectious diseases and use of antimicrobial agents from the National Patient Register and the Danish Prescription Register. Associations were tested using Cox proportional hazards models. During 12 years of follow-up, we observed a U-shaped association between baseline BMI and later hospitalization for 1) any infectious disease and 2) infections of the respiratory tract, whereas a dose-response relationship was seen for skin infections. The most pronounced associations were seen for acute upper respiratory infections at multiple and unspecified sites (underweight (BMI
PubMed ID
27188940 View in PubMed
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Cancer risk in inflammatory bowel disease according to patient phenotype and treatment: a Danish population-based cohort study.

https://arctichealth.org/en/permalink/ahliterature107771
Source
Am J Gastroenterol. 2013 Dec;108(12):1869-76
Publication Type
Article
Date
Dec-2013
Author
Tine Jess
Erzsébet Horváth-Puhó
Jan Fallingborg
Henrik H Rasmussen
Bent A Jacobsen
Author Affiliation
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Source
Am J Gastroenterol. 2013 Dec;108(12):1869-76
Date
Dec-2013
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Child
Child, Preschool
Denmark - epidemiology
Female
Humans
Infant
Inflammatory Bowel Diseases - epidemiology
Male
Middle Aged
Neoplasms - epidemiology
Phenotype
Registries
Risk
Abstract
Population-based studies of site-specific cancer risk in patients with inflammatory bowel disease (IBD) according to IBD phenotype and treatment are lacking. We studied cancer risk in a well-characterized population-based IBD cohort from North Jutland County, Denmark.
A total of 1,515 patients were diagnosed with ulcerative colitis (UC) and 810 with Crohn's disease (CD) during 1978-2002. Patients were followed until 31 December 2010 for occurrence of incident cancer, identified in the Danish Cancer Registry. Observed numbers of cancer were compared with expected numbers (based on age- and sex-specific background rates) and presented as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs).
Patients with UC were not at increased risk of cancer overall (SIR, 1.12; 95% CI, 0.97-1.28) despite increased risk of prostate cancer (SIR, 1.82; 95% CI, 1.17-2.71). Patients with CD had a 55% increased risk of cancer overall (SIR, 1.55; 95% CI, 1.29-1.84) related to young age, colonic disease, smoking, and thiopurine exposure. Patients were at increased risk of small bowel cancer (SIR, 15.18; 95% CI, 1.84-54.78), lung cancer (SIR, 2.13; 95% CI, 1.19-3.52 (associated with female gender and smoking)), colorectal cancer in males (SIR, 2.43; 95% CI, 1.05-4.78), cervical dysplasia (SIR, 1.65; 95% CI, 1.10-2.37 (associated with young age at diagnosis, smoking, 5-aminosalicylic acid, and thiopurine exposure)), and non-Hodgkin lymphoma (SIR, 3.43; 95% CI, 1.38-7.07 (unrelated to thiopurine exposure)).
Patients with CD, but not UC, have an overall excess risk of cancer. Clinical characteristics of IBD patients at excess risk differ by cancer subtype.
PubMed ID
23978954 View in PubMed
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Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979-2011.

https://arctichealth.org/en/permalink/ahliterature258194
Source
Gut. 2014 Oct;63(10):1607-16
Publication Type
Article
Date
Oct-2014
Author
Christine Rungoe
Ebbe Langholz
Mikael Andersson
Saima Basit
Nete M Nielsen
Jan Wohlfahrt
Tine Jess
Author Affiliation
Department of Epidemiology Research, National Center for Health Data and Disease Control, Copenhagen, Denmark.
Source
Gut. 2014 Oct;63(10):1607-16
Date
Oct-2014
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Aged, 80 and over
Azathioprine - therapeutic use
Cohort Studies
Colitis, Ulcerative - drug therapy - surgery - therapy
Crohn Disease - drug therapy - surgery - therapy
Denmark
Digestive System Surgical Procedures - trends
Drug Utilization - statistics & numerical data
Female
Glucocorticoids - therapeutic use
Humans
Male
Mesalamine - therapeutic use
Middle Aged
Risk factors
Survival Analysis
Young Adult
Abstract
Treatment possibilities have changed in inflammatory bowel disease (IBD). We assessed changes in medical treatment and surgery over time and impact of medications on risk of surgery in a population-based cohort.
48 967 individuals were diagnosed with IBD (Crohn's disease (CD), 13 185; ulcerative colitis (UC), 35 782) during 1979-2011. Cumulative probability of receiving 5-aminosalicylic acids (5-ASA), topical, oral corticosteroids, thiopurines, and tumour necrosis factor-a (TNF-a) blockers, and of first minor or major surgery according to period of diagnosis, was estimated. Medication use and risk of surgery was examined by Cox regression.
5-year cumulative probability of first major surgery decreased from 44.7% in cohort (1979-1986) to 19.6% in cohort (2003-2011) (p?1 year.
Parallel to an increasing use of thiopurines and TNF-a blockers in IBD over time, a persistent significant decrease in surgery rates was observed along with a significant decrease in use of 5-ASA and corticosteroids. However, no convincing surgery-sparing effect of newer medications was found.
Notes
Comment In: Gut. 2014 Oct;63(10):1529-3024287275
PubMed ID
24056767 View in PubMed
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Colonoscopy surveillance for dysplasia and colorectal cancer in patients with inflammatory bowel disease.

https://arctichealth.org/en/permalink/ahliterature265408
Source
Dan Med J. 2015 Jan;62(1):B4995
Publication Type
Article
Date
Jan-2015
Author
Claus Aalykke
Michael Dam Jensen
Jan Fallingborg
Tine Jess
Ebbe Langholz
Søren Meisner
Nynne Nyboe Andersen
Lene Buhl Riis
Ole Østergaard Thomsen
Anders Tøttrup
Source
Dan Med J. 2015 Jan;62(1):B4995
Date
Jan-2015
Language
English
Publication Type
Article
Keywords
Age of Onset
Biopsy - methods
Colitis, Ulcerative - complications
Colon - pathology
Colonoscopy - methods
Colorectal Neoplasms - diagnosis
Crohn Disease - complications
Denmark
Female
Humans
Hyperplasia - diagnosis
Inflammatory Bowel Diseases - complications
Intestinal Mucosa - pathology
Male
Population Surveillance - methods
Time Factors
Abstract
The risk of colorectal cancer (CRC) and dysplasia in patients with inflammatory bowel disease (IBD) has been highly debated as risk estimates from different studies vary greatly. The present national Danish guideline on colonoscopy surveillance for dysplasia and colorectal cancer in patients with IBD is based on a thorough review of existing literature with particular focus on recent studies from Denmark revealing a lower risk of CRC than previously assumed. The overall risk of CRC in the Danish IBD population does not appear to be different from that of the background population; however, in some subgroups of patients the risk is increased. These subgroups of patients, who should be offered colonoscopy surveillance, include patients with ulcerative colitis having extensive disease and a long disease duration (10-13 years); early age at onset (less than 19 years of age) of ulcerative colitis; and patients with ulcerative colitis as well as Crohn's disease with a concomitant diagnosis of primary sclerosing cholangitis. A colonoscopy surveillance program is recommended in these subgroups with intervals ranging from every 3-6 months to every 5 years, using chromoendoscopy with targeted biopsies of the lesion and adjacent mucosa, instead of conventional colonoscopy with random biopsies. Preferably, the colonoscopy should be performed during clinical remission. If a lesion is detected the endoscopical resectability together with the pathology of the lesion and the adjacent mucosa determine how the lesion should be treated.
PubMed ID
25557336 View in PubMed
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A cross-sectional study on trans-fatty acids and risk markers of CHD among middle-aged men representing a broad range of BMI.

https://arctichealth.org/en/permalink/ahliterature101529
Source
Br J Nutr. 2011 May 18;:1-8
Publication Type
Article
Date
May-18-2011
Author
Birgit M Nielsen
Marie M Nielsen
Marianne U Jakobsen
Carina J Nielsen
Claus Holst
Thomas M Larsen
Nathalie T Bendsen
Anette Bysted
Torben Leth
David M Hougaard
Kristin Skogstrand
Arne Astrup
Thorkild I A Sørensen
Tine Jess
Author Affiliation
Institute of Preventive Medicine, Copenhagen University Hospitals, Copenhagen Capital Region, Øster Søgade 18, DK-1357 Copenhagen K, Denmark.
Source
Br J Nutr. 2011 May 18;:1-8
Date
May-18-2011
Language
English
Publication Type
Article
Abstract
Intake of trans-fatty acids (TFA), especially industrially produced TFA (I-TFA), has been associated with the risk of CHD through influence on serum lipid levels. Other causal pathways remain less investigated. In the present cross-sectional study of middle-aged men representing a broad range of BMI, the association between intake of TFA, I-TFA and ruminant TFA (R-TFA) and obesity-associated risk markers of CHD was assessed. The study comprised 393 Danish men (median age 49 years) with a median BMI of 28·4 kg/m2. Intake of TFA was estimated based on 7 d dietary records, whereas outcomes of interest (waist circumference, sagittal abdominal diameter, percentage of truncal fat, C-reactive protein, IL-6, blood lipids, blood pressure, HbA1c and insulin sensitivity index) were obtained through clinical examination. The associations were assessed by linear regression analysis. The median intake of total TFA among the 393 men was 1·3 g/d, covering a daily I-TFA intake of 0·4 g (10-90th percentile 0·0-1·0) and R-TFA intake of 0·9 g (10-90th percentile 0·4-1·8). Intake of these amounts of TFA showed no significant associations with abdominal fatness, inflammatory markers, blood lipids, blood pressure and insulin homeostasis. Among middle-aged men with a generally low intake of TFA, neither I-TFA nor R-TFA was significantly related to obesity-associated risk markers of CHD. The decreased average intake of I-TFA in Denmark since 1995 is suggested to effectively prevent occurrence of the adverse metabolic changes and health consequences, which have formerly been observed in relation to, especially, I-TFA intake.
PubMed ID
21736833 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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Decreasing risk of colorectal cancer in patients with inflammatory bowel disease over 30 years.

https://arctichealth.org/en/permalink/ahliterature125048
Source
Gastroenterology. 2012 Aug;143(2):375-81.e1; quiz e13-4
Publication Type
Article
Date
Aug-2012
Author
Tine Jess
Jacob Simonsen
Kristian Tore Jørgensen
Bo Vestergaard Pedersen
Nete Munk Nielsen
Morten Frisch
Author Affiliation
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. tjs@ssi.dk
Source
Gastroenterology. 2012 Aug;143(2):375-81.e1; quiz e13-4
Date
Aug-2012
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Age of Onset
Aged
Aged, 80 and over
Child
Child, Preschool
Cholangitis, Sclerosing - complications
Cohort Studies
Colorectal Neoplasms - epidemiology - etiology
Denmark - epidemiology
Female
Follow-Up Studies
Humans
Incidence
Infant
Inflammatory Bowel Diseases - complications
Male
Middle Aged
Poisson Distribution
Registries
Regression Analysis
Risk
Young Adult
Abstract
The risk for colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) could have changed over time, with changes in treatment options. We studied CRC risk in a nationwide cohort of 47,374 Danish patients with IBD over a 30-year period.
We determined relative risk (RR) values using Poisson regression-derived incidence rate ratios of CRC from 1 year after IBD diagnosis, adjusted for age, sex, and calendar time. We compared incidence of CRC among patients with IBD vs individuals without IBD.
During 178 million person-years of follow-up evaluation, 268 patients with ulcerative colitis (UC) and 70 patients with Crohn's disease (CD) developed CRC. The overall risk of CRC among patients with UC was comparable with that of the general population (RR, 1.07; 95% confidence interval [CI], 0.95-1.21). However, patients diagnosed with UC in childhood or as adolescents, those with long duration of disease, and those with concomitant primary sclerosing cholangitis were at increased risk. For patients with UC, the overall RR for CRC decreased from 1.34 (95% CI, 1.13-1.58) in 1979-1988 to 0.57 (95% CI, 0.41-0.80) in 1999-2008. Among patients with CD, the overall RR for CRC was 0.85 (95% CI, 0.67-1.07), which did not change over time.
A diagnosis of UC or CD no longer seems to increase patients' risk of CRC, although subgroups of patients with UC remain at increased risk. The decreasing risk for CRC from 1979 to 2008 might result from improved therapies for patients with IBD.
Notes
Comment In: Gastroenterology. 2012 Aug;143(2):288-9022727998
Comment In: Gastroenterology. 2013 Mar;144(3):e22-323357064
Comment In: Gastroenterology. 2013 Mar;144(3):e21-223357065
Comment In: Gastroenterology. 2012 Nov;143(5):e20; author reply e20-123000225
PubMed ID
22522090 View in PubMed
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Disease concordance, zygosity, and NOD2/CARD15 status: follow-up of a population-based cohort of Danish twins with inflammatory bowel disease.

https://arctichealth.org/en/permalink/ahliterature63138
Source
Am J Gastroenterol. 2005 Nov;100(11):2486-92
Publication Type
Article
Date
Nov-2005
Author
Tine Jess
Lene Riis
Cathrine Jespersgaard
Lotte Hougs
Paal Skytt Andersen
Marianne K Orholm
Vibeke Binder
Pia Munkholm
Author Affiliation
Department of Medical Gastroenterology C, Herlev Hospital, University of Copenhagen, Denmark.
Source
Am J Gastroenterol. 2005 Nov;100(11):2486-92
Date
Nov-2005
Language
English
Publication Type
Article
Keywords
Adult
Alleles
Cohort Studies
Colitis, Ulcerative - genetics
Comparative Study
Crohn Disease - genetics
DNA - analysis
Denmark
Diseases in Twins
Female
Follow-Up Studies
Gene Frequency
Humans
Inflammatory Bowel Diseases - genetics
Intracellular Signaling Peptides and Proteins - genetics
Male
Middle Aged
Mutation - genetics
Phenotype
Population Surveillance
Research Support, Non-U.S. Gov't
Retrospective Studies
Twins, Dizygotic - genetics
Twins, Monozygotic - genetics
Abstract
OBJECTIVES: A Danish cohort of twins with inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), has previously been collected. The aim of the present study was to reassess this cohort in order to compare clinical characteristics in concordant versus discordant twin pairs, test twin zygosity genetically, follow-up on disease concordance, and examine NOD2/CARD15 genetic status. METHODS: The Danish cohort is one of two population-based cohorts worldwide and consists of 103 twin pairs. After median 13 yr of follow-up, all twins were contacted and hospital files were scrutinized to reassess disease concordance and obtain phenotype data. DNA was obtained from 123 twins for analysis of zygosity and prevalence of the three common NOD2/CARD15 mutations. RESULTS: Zygosity tested genetically was consistent with the former assessment based on questionnaires. The proband concordance for CD remained fairly stable: 63.6% among monozygotic (MZ) twins and 3.6% among dizygotic (DZ) twins. Clinical characteristics were similar in twins from concordant versus discordant pairs. Forty-four percent of patients with CD were positive for >or=1 mutant allele of NOD2/CARD15 compared to 2% of UC patients (p
PubMed ID
16279904 View in PubMed
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