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Article ; Online: Elevated plasma triglycerides increase risk of psoriasis: A cohort and Mendelian randomization study.

Greve, Anders M / Wulff, Anders B / Bojesen, Stig E / Nordestgaard, Børge G

2024

Abstract: Background: It is increasingly clear that triglyceride-rich lipoproteins are proinflammatory and cause low-grade systemic inflammation. However, it is currently unknown whether elevated plasma triglycerides are causally related to development of ... ...

Abstract	Background: It is increasingly clear that triglyceride-rich lipoproteins are proinflammatory and cause low-grade systemic inflammation. However, it is currently unknown whether elevated plasma triglycerides are causally related to development of psoriasis, a skin disorder driven by chronic inflammation. Objective: To determine if elevated plasma triglycerides are associated with increased risk of psoriasis in observational and Mendelian randomization analysis. Methods: Consecutive individuals from the Copenhagen General Population Study (CGPS) were included. We used plasma triglycerides (n = 108,043) and a weighted triglyceride allele score (n = 92,579) on nine known triglyceride-altering genetic variants. Genetic results were replicated in 337,159 individuals from the UK biobank. Psoriasis was ICD10-code hospital contact in main analyses, and prescription of topical antipsoriatics for mild psoriasis in sensitivity analysis. Results: During a median 9.3 years (0.1-15.1) of follow-up (from 2003-2015 through 2018), 855 (1%) individuals were diagnosed with psoriasis by ICD-10 in observational analysis and 772 (1%) in Mendelian randomization analysis. In observational analysis, multivariable adjusted hazard ratio for psoriasis by ICD-10 were 1.26 (95% CI:1.15-1.39) per doubling in plasma triglycerides with a corresponding causal, genetic risk ratio of 2.10 (1.30-3.38). Causality was confirmed in the UK biobank. Results were similar but slightly attenuated when we used topical antipsoriatics prescription for mild psoriasis. Conclusion: Elevated plasma triglycerides are associated with increased risk of psoriasis in observational and Mendelian randomization analysis.
Language	English
Publishing date	2024-02-27
Publishing country	England
Document type	Journal Article
ZDB-ID	80076-4
ISSN	1365-2133 ; 0007-0963
ISSN (online)	1365-2133
ISSN	0007-0963
DOI	10.1093/bjd/ljae089
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Article ; Online: [Genomic medicine and cancer].

Bojesen, Stig E

Ugeskrift for laeger

2019 Volume 181, Issue 7A

Abstract: Our genomic understanding of cancer evolves quickly, driven by technological advances. Insights are added every day, but their interpretations are based on fundamental hypotheses on heredity and cell biology formulated more than 100 years ago. Genomic ... ...

Abstract	Our genomic understanding of cancer evolves quickly, driven by technological advances. Insights are added every day, but their interpretations are based on fundamental hypotheses on heredity and cell biology formulated more than 100 years ago. Genomic medicine is already in some use, but data from extremely large experiments of 100,000s of patients, controls, and tumours will alter the whole management of cancer; from early detection programmes before diagnosis, to efficient diagnostics, targeted treatment, response surveillance and monitoring of relapse.
MeSH term(s)	Genomics ; Humans ; Neoplasms/genetics ; Neoplasms/therapy ; Precision Medicine
Language	Danish
Publishing date	2019-04-04
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	124102-3
ISSN	1603-6824 ; 0041-5782
ISSN (online)	1603-6824
ISSN	0041-5782
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Article ; Online: Adherence to general national dietary guidelines and risk of psoriasis: results from a general population study of 105,332 individuals.

Näslund-Koch, Charlotte / Kjeldsen, Emilie W / Vedel-Krogh, Signe / Bojesen, Stig E / Skov, Lone

Clinical and experimental dermatology

2024

Abstract: Background: It is unknown if an unhealthy diet can affect the risk of developing psoriasis.: Objectives: We hypothesised that individuals with an unhealthy diet have increased risk of prevalent and incident psoriasis.: Methods: We included 105,332 ...

Abstract	Background: It is unknown if an unhealthy diet can affect the risk of developing psoriasis. Objectives: We hypothesised that individuals with an unhealthy diet have increased risk of prevalent and incident psoriasis. Methods: We included 105,332 adults from the Copenhagen General Population Study, who were invited between 2003 and 2015. Response-rate was 43%. An unhealthy versus healthy diet was defined according to adherence to general national dietary guidelines. The participants were grouped into low, intermediate, and high adherence to general national dietary guidelines based on information from a food frequency questionnaire. Identification of psoriasis was made using ICD codes. Results: Of the 105,332 individuals, 580 had a diagnosis of psoriasis at the time of enrolment and 640 received a diagnosis during the median follow-up of 9 years. Risk of prevalent psoriasis increased according to non-adherence to general national dietary guidelines in a stepwise manner with an age and sex adjusted odds ratio of 1.70 (95% confidence interval 1.26-2.30) in individuals with low vs. high adherence to dietary guidelines. Results were similar in a multivariable adjusted model. Prospective analyses adjusted for age and sex showed a weak association between non-adherence to dietary guidelines and risk of incident psoriasis (P for trend 0.04). This association disappeared, when adjusting for multiple confounders (P for trend 0.50). Conclusions: Although individuals with psoriasis have an unhealthier diet, diet alone does not appear to independently increase the risk of developing psoriasis.
Language	English
Publishing date	2024-03-28
Publishing country	England
Document type	Journal Article
ZDB-ID	195504-4
ISSN	1365-2230 ; 0307-6938
ISSN (online)	1365-2230
ISSN	0307-6938
DOI	10.1093/ced/llae091
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Zs.A 1278: Show issues

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Article ; Online: AHRR (cg05575921) Methylation Safely Improves Specificity of Lung Cancer Screening Eligibility Criteria: A Cohort Study.

Jacobsen, Katja Kemp / Schnohr, Peter / Jensen, Gorm Boje / Bojesen, Stig E

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

2022 Volume 31, Issue 4, Page(s) 758–765

Abstract: Background: Screening reduces lung cancer mortality, but specificities of eligibility criteria are low. We tested if leukocyte AHRR(cg05575921) methylation improves specificity of lung cancer screening eligibility criteria.: Methods: A total of 9,206 ...

Abstract	Background: Screening reduces lung cancer mortality, but specificities of eligibility criteria are low. We tested if leukocyte AHRR(cg05575921) methylation improves specificity of lung cancer screening eligibility criteria. Methods: A total of 9,206 and 5,370 individuals of the 1991 to 1994 and 2001 to 2003 examinations of the Copenhagen City Heart Study, Denmark, were followed for lung cancer within 5 years after examination and mortality. Screening eligibility criteria (DANTE, DLCST, ITALUNG, LUSI, NELSON, NLST, and PLCOM2012) were evaluated, and AHRR (cg05575921) methylation extent at different methylation cut points was added. The model with the lowest number of eligible individuals per 5-year lung cancer was validated within the 2001 to 2003 examination. Results: Eligibility criteria identified risk-groups ranging from 3,182 (DANTE) to 1,641 (ITALUNG) individuals. The positive predictive value was highest for PLCOM2012 (3.2%), while DANTE showed the highest negative predictive value (99.7%). Adding AHRR (cg05575921) methylation led to higher specificities for all criteria. Number of eligible individuals per 5-year lung cancer varied from 38 (NELSON) to 27 (NLST) with AHRR (cg05575921) methylation <55%. This last model led to a 21.9% lower screening burden and increased (P < 0.05) specificity of 84.0%. Findings were reproduced among the 5,334 individuals of the 2001 to 2003 examination. Conclusions: Adding AHRR (cg05575921) methylation on top of current eligibility criteria for lung cancer screening improves specificity by excluding those individuals with the lowest risk. Impact: The results point toward a potential clinical use of AHRR (cg05575921) methylation, which is a cost-effective measurement compared with lung CT scanning, to provide additional predictive risk information to identify eligible smokers for lung cancer screening. See related commentary by Hung, p. 698.
MeSH term(s)	Basic Helix-Loop-Helix Transcription Factors ; Cohort Studies ; DNA Methylation ; Early Detection of Cancer/methods ; Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/genetics ; Mass Screening/methods ; Repressor Proteins/genetics ; Smoking
Chemical Substances	AHRR protein, human ; Basic Helix-Loop-Helix Transcription Factors ; Repressor Proteins
Language	English
Publishing date	2022-01-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	1153420-5
ISSN	1538-7755 ; 1055-9965
ISSN (online)	1538-7755
ISSN	1055-9965
DOI	10.1158/1055-9965.EPI-21-1059
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Article ; Online: Telomere length and risk of cirrhosis, hepatocellular carcinoma, and cholangiocarcinoma in 63,272 individuals from the general population.

Gellert-Kristensen, Helene / Bojesen, Stig E / Tybjærg Hansen, Anne / Stender, Stefan

Hepatology (Baltimore, Md.)

2023 Volume 79, Issue 4, Page(s) 857–868

Abstract: Background and aims: Inherited short telomeres are associated with a risk of liver disease, whereas longer telomeres predispose to cancer. The association between telomere length and risk of HCC and cholangiocarcinoma remains unknown.: Approach and ... ...

Abstract	Background and aims: Inherited short telomeres are associated with a risk of liver disease, whereas longer telomeres predispose to cancer. The association between telomere length and risk of HCC and cholangiocarcinoma remains unknown. Approach and results: We measured leukocyte telomere length using multiplex PCR in 63,272 individuals from the Danish general population. Telomere length and plasma ALT concentration were not associated (β = 4 ×10 -6 , p -value = 0.06) in a linear regression model, without any signs of a nonlinear relationship. We tested the association between telomere length and risk of cirrhosis, HCC, and cholangiocarcinoma using Cox regression. During a median follow-up of 11 years, 241, 76, and 112 individuals developed cirrhosis, HCC, and cholangiocarcinoma, respectively. Telomere length and risk of cirrhosis were inversely and linearly associated ( p -value = 0.004, p for nonlinearity = 0.27). Individuals with telomeres in the shortest vs. longest quartile had a 2.25-fold higher risk of cirrhosis. Telomere length and risk of HCC were nonlinearly associated ( p -value = 0.009, p -value for nonlinearity = 0.01). This relationship resembled an inverted J-shape, with the highest risk observed in individuals with short telomeres. Individuals with telomeres in the shortest versus longest quartile had a 2.29-fold higher risk of HCC. Telomere length was inversely and linearly associated with the risk of cholangiocarcinoma. Individuals with telomeres in the shortest versus longest quartile had a 1.86-fold higher risk of cholangiocarcinoma. Conclusions: Shorter telomere length is associated with a higher risk of cirrhosis, HCC, and cholangiocarcinoma.
MeSH term(s)	Humans ; Carcinoma, Hepatocellular/epidemiology ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Risk Factors ; Liver Neoplasms/epidemiology ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Leukocytes ; Liver Cirrhosis/genetics ; Liver Cirrhosis/pathology ; Cholangiocarcinoma/epidemiology ; Cholangiocarcinoma/genetics ; Cholangiocarcinoma/pathology ; Bile Duct Neoplasms/epidemiology ; Bile Duct Neoplasms/genetics ; Bile Duct Neoplasms/pathology ; Bile Ducts, Intrahepatic/pathology ; Telomere/genetics
Language	English
Publishing date	2023-09-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1097/HEP.0000000000000608
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Zs.A 1660: Show issues

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Article ; Online: Plasma Vitamin D Is Not Associated with Moderate-to-Severe Psoriasis: Results from Danish General Population Studies.

Näslund-Koch, Charlotte / Vedel-Krogh, Signe / Bojesen, Stig E / Skov, Lone

The Journal of investigative dermatology

2023 Volume 143, Issue 10, Page(s) 2068–2071

MeSH term(s)	Humans ; Vitamin D ; Vitamins ; Psoriasis/complications ; Denmark/epidemiology ; Vitamin D Deficiency/epidemiology ; Vitamin D Deficiency/complications
Chemical Substances	Vitamin D (1406-16-2) ; Vitamins
Language	English
Publishing date	2023-04-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2023.04.004
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Article ; Online: Correlation between allostatic load index and cumulative mortality: a register-based study of Danish municipalities.

Bruun-Rasmussen, Neda Esmailzadeh / Napolitano, George / Bojesen, Stig E / Ellervik, Christina / Holmager, Therese Lucia Friis / Rasmussen, Knud / Lynge, Elsebeth

BMJ open

2024 Volume 14, Issue 2, Page(s) e075697

Abstract: Objectives: The aim of this study was to examine population-based allostatic load (AL) indices as an indicator of community health across 14 municipalities in Denmark.: Design: Register-based study.: Setting: Data derived from: the Lolland-Falster ...

Abstract	Objectives: The aim of this study was to examine population-based allostatic load (AL) indices as an indicator of community health across 14 municipalities in Denmark. Design: Register-based study. Setting: Data derived from: the Lolland-Falster Health Study, the Copenhagen General Population Study and the Danish General Suburban Population Study. Nine biomarkers (systolic blood pressure, diastolic blood pressure, pulse rate, total serum cholesterol, high-density lipoprotein cholesterol, waist-to-hip ratio, triglycerides, C-reactive protein and serum albumin) were divided into high-risk and low-risk values based on clinically accepted criteria, and the AL index was defined as the average between the nine values. All-cause mortality data were obtained from Statistics Denmark. Participants: We examined a total of 106 808 individuals aged 40-79 years. Primary outcome measure: Linear regression models were performed to investigate the association between mean AL index and cumulative mortality risk. Results: Mean AL index was higher in men (range 2.3-3.3) than in women (range 1.7-2.6). We found AL index to be strongly correlated with the cumulative mortality rate, correlation coefficient of 0.82. A unit increase in mean AL index corresponded to an increase in the cumulative mortality rate of 19% (95% CI 13% to 25%) for men, and 16% (95% CI 8% to 23%) for women but this difference was not statistically significant. The overall mean increase in cumulative mortality rate for both men and women was 17% (95% CI 14% to 20%). Conclusions: Our findings indicate the population-based AL index to be a strong indicator of community health, and suggest identification of targets for reducing AL.
MeSH term(s)	Male ; Humans ; Female ; Cities ; Allostasis/physiology ; Biomarkers ; Cholesterol, HDL ; Denmark/epidemiology
Chemical Substances	Biomarkers ; Cholesterol, HDL
Language	English
Publishing date	2024-02-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-075697
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Article ; Online: Self-reported and genetically predicted coffee consumption and smoking in dementia: A Mendelian randomization study.

Nordestgaard, Ask T / Nordestgaard, Børge G / Frikke-Schmidt, Ruth / Juul Rasmussen, Ida / Bojesen, Stig E

Atherosclerosis

2022 Volume 348, Page(s) 36–43

Abstract: Background and aims: Studies of self-reported coffee consumption and smoking on risk of dementia have shown results conflicting with two-sample Mendelian randomization studies. We tested the hypotheses that coffee consumption and smoking influence risk ... ...

Abstract	Background and aims: Studies of self-reported coffee consumption and smoking on risk of dementia have shown results conflicting with two-sample Mendelian randomization studies. We tested the hypotheses that coffee consumption and smoking influence risk of dementia using observational and one-sample Mendelian randomization designs with individual level data. Methods: We included 114,551 individuals from two Danish general population cohorts (median age 58 years). First, we tested whether high self-reported coffee consumption/smoking were associated with risk of dementia. Second, whether genetically predicted high coffee consumption/smoking due to variation near CYP1A1/AHR/CHRNA3 genes were associated with risk of dementia. Results: We observed 3,784 dementia events. Moderate self-reported coffee consumption was associated with low risk of all dementia and non-Alzheimer's dementia, with a similar trend for Alzheimer's disease. Genetically predicted high coffee consumption was associated with high risk of all dementia (hazard ratio [95% confidence interval] per +1 cup/day: 1.20 [1.01-1.42]), with a similar trend for non-Alzheimer's dementia (1.23 [0.95-1.53]). High self-reported smoking was associated with high risk of non-Alzheimer's dementia. High genetically predicted smoking was associated with a trend towards high risk of all dementia and Alzheimer's disease (hazard ratios per +1 pack-year: 1.04 [0.96-1.11]) and 1.06 [0.97-1.16]). Conclusions: Moderate self-reported coffee consumption was associated with low risk of all and non-Alzheimer's dementia, while high genetically predicted coffee consumption was associated with a trend towards the opposite. High self-reported smoking was associated with high risk of non-Alzheimer's dementia, with a similar trend for genetically predicted smoking on all dementia and Alzheimer's disease.
MeSH term(s)	Alzheimer Disease ; Coffee ; Humans ; Mendelian Randomization Analysis ; Middle Aged ; Risk Factors ; Self Report ; Smoking/adverse effects ; Smoking/genetics
Chemical Substances	Coffee
Language	English
Publishing date	2022-03-22
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80061-2
ISSN	1879-1484 ; 0021-9150
ISSN (online)	1879-1484
ISSN	0021-9150
DOI	10.1016/j.atherosclerosis.2022.03.022
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Article ; Online: Prognostic Value of Pretreatment Plasma C-Reactive Protein in Patients with Early-Stage Breast Cancer.

Andersen, Høgni H / Bojesen, Stig E / Johansen, Julia S / Ejlertsen, Bent / Berg, Tobias / Tuxen, Malgorzata / Madsen, Kasper / Danø, Hella / Flyger, Henrik / Jensen, Maj-Britt / Nielsen, Dorte L

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

2024 Volume 33, Issue 5, Page(s) 662–670

Abstract: Background: Breast cancer incidence is now the highest among all cancers and accountable for 6.6% of all cancer-related deaths worldwide. Studies of the prognostic utility of plasma C-reactive protein (CRP) measurement in early-stage breast cancer have ... ...

Abstract	Background: Breast cancer incidence is now the highest among all cancers and accountable for 6.6% of all cancer-related deaths worldwide. Studies of the prognostic utility of plasma C-reactive protein (CRP) measurement in early-stage breast cancer have given discrepant results. Methods: We identified 6,942 patients in the Danish Breast Cancer Cooperative Group database with early-stage breast cancer diagnosed between 2002 and 2016 who had a measure of pretreatment plasma CRP. Outcomes were recurrence-free interval and survival for a period up to 10 years. We analyzed associations with plasma CRP using Fine-Gray proportional subdistribution hazards model with recurrence-free interval. Data on plasma CRP were analyzed per doubling of concentration and in relation to CRP levels of <3 mg/L, 3 to 10 mg/L, and >10 mg/L and stratified according to standard clinical parameters in sensitivity analyses. Results: A doubling of the plasma CRP concentration was associated with increased risk of recurrence (multivariate adjusted HR, 1.05; 95% CI, 1.01-1.08) and shorter survival (HR, 1.13; 95% CI, 1.09-1.16) in multivariate analyses. Survival was shorter in patients with plasma CRP levels of 3 to 10 and >10 mg/L versus <3 mg/L, with multivariate adjusted HRs of 1.30; 95% CI, 1.17-1.45 and 1.65; 95% CI, 1.39-1.95, respectively. Conclusions: Elevated plasma CRP measured before treatment in patients with early-stage breast cancer is an independent biomarker of increased risk of recurrence and early death. Impact: CRP measures before treatment might be used to individualize follow-up of patients with early-stage breast cancer.
MeSH term(s)	Humans ; Breast Neoplasms/blood ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology ; Female ; C-Reactive Protein/metabolism ; C-Reactive Protein/analysis ; Middle Aged ; Prognosis ; Aged ; Neoplasm Staging ; Biomarkers, Tumor/blood ; Adult ; Neoplasm Recurrence, Local/blood ; Neoplasm Recurrence, Local/epidemiology ; Denmark/epidemiology
Chemical Substances	C-Reactive Protein (9007-41-4) ; Biomarkers, Tumor
Language	English
Publishing date	2024-01-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1153420-5
ISSN	1538-7755 ; 1055-9965
ISSN (online)	1538-7755
ISSN	1055-9965
DOI	10.1158/1055-9965.EPI-23-1299
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Article ; Online: AHRR hypomethylation as an epigenetic marker of smoking history predicts risk of myocardial infarction in former smokers.

Langsted, Anne / Bojesen, Stig E / Stroes, Erik S G / Nordestgaard, Børge G

Atherosclerosis

2020 Volume 312, Page(s) 8–15

Abstract: Background and aims: Smoking causes cardiovascular disease. AHRR hypomethylation at the cg05575921 site is associated with active and former smoking status at baseline, and cumulative amount of tobacco smoked. We tested the hypothesis that AHRR ... ...

Abstract	Background and aims: Smoking causes cardiovascular disease. AHRR hypomethylation at the cg05575921 site is associated with active and former smoking status at baseline, and cumulative amount of tobacco smoked. We tested the hypothesis that AHRR cg05575921 hypomethylation as an epigenetic marker of smoking history predicts the risk of myocardial infarction in former smokers. Methods: We included 10,510 individuals with methylation extent measurements and information on smoking status from the Copenhagen City Heart Study (CCHS), a prospective, cohort study of the general population carried out from 1991 to 2003. The endpoint myocardial infarction was retrieved from the national Danish Patient Registry and the national Danish Causes of Death Registry. Results: For individuals in the 1st (lowest) quartile of AHRR cg05575921 methylation (≤49% methylation extent), 99% were ever smokers at baseline (active and former smokers combined) compared to 42% in the 4th (highest) quartile (>62% methylation extent). For former smokers, the cumulative incidence of myocardial infarction was higher in the lowest methylation extent (1st-50th percentile) compared to the highest methylation extent (51st-100th percentile). Compared to never smokers, the multivariable adjusted subhazard ratio for myocardial infarction was 1.09 (95%CI:0.88-1.35) for former smokers with the highest methylation degree, 1.38 (1.06-1.80) for active smokers with the highest methylation extent, 1.39 (1.08-1.78) for former smokers with the lowest methylation extent, and 1.61 (1.35-1.92) for active smokers with the lowest methylation extent. Conclusions: AHRR cg05575921 hypomethylation as an epigenetic marker of smoking history predicts risk of myocardial infarction, particularly in former smokers. Further, AHRR hypomethylation, regardless of smoking status, was associated with increased risk of myocardial infarction.
MeSH term(s)	Basic Helix-Loop-Helix Transcription Factors/genetics ; Cohort Studies ; DNA Methylation ; Epigenesis, Genetic ; Humans ; Myocardial Infarction/diagnosis ; Myocardial Infarction/epidemiology ; Myocardial Infarction/genetics ; Prospective Studies ; Repressor Proteins/genetics ; Risk Factors ; Smokers ; Smoking/adverse effects
Chemical Substances	AHRR protein, human ; Basic Helix-Loop-Helix Transcription Factors ; Repressor Proteins
Language	English
Publishing date	2020-09-07
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80061-2
ISSN	1879-1484 ; 0021-9150
ISSN (online)	1879-1484
ISSN	0021-9150
DOI	10.1016/j.atherosclerosis.2020.08.034
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