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ß2-adrenergic receptor Thr164Ile polymorphism, obesity, and diabetes: comparison with FTO, MC4R, and TMEM18 polymorphisms in more than 64,000 individuals.

https://arctichealth.org/en/permalink/ahliterature125626
Source
J Clin Endocrinol Metab. 2012 Jun;97(6):E1074-9
Publication Type
Article
Date
Jun-2012
Author
Mette Thomsen
Morten Dahl
Anne Tybjærg-Hansen
Børge G Nordestgaard
Author Affiliation
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
Source
J Clin Endocrinol Metab. 2012 Jun;97(6):E1074-9
Date
Jun-2012
Language
English
Publication Type
Article
Keywords
Adult
Body mass index
Cohort Studies
Denmark - epidemiology
Diabetes Mellitus - epidemiology - genetics
Female
Genetic Predisposition to Disease - epidemiology - genetics
Genotype
Humans
Male
Membrane Proteins - genetics
Obesity - epidemiology - genetics
Polymorphism, Single Nucleotide - genetics
Proteins - genetics
Receptor, Melanocortin, Type 4 - genetics
Receptors, Adrenergic, beta-2 - genetics
Risk factors
Abstract
The ß(2)-adrenergic receptor (ADRB2) influences regulation of energy balance by stimulating catecholamine-induced lipolysis in adipose tissue. The rare functional ADRB2rs1800888(Thr164Ile) polymorphism could therefore influence risk of obesity and subsequently diabetes.
We tested the hypothesis that the ADRB2rs1800888(Thr164Ile) polymorphism associates with risk of obesity and diabetes and compared effect sizes with those of FTO(rs9939609), MC4R(rs17782313), and TMEM18(rs6548238).
We conducted a population-based cohort study in Copenhagen, Denmark.
We genotyped more than 64,000 individuals from the Danish general population.
We evaluated body mass index (BMI), obesity (BMI =30 kg/m(2)), and diabetes.
Rare allele frequencies were 0.02 for T for ADRB2rs1800888(Thr164Ile), 0.40 for A for FTOrs9939609, 0.25 for C for MC4Rrs17782313, and 0.20 for T for TMEM18rs6548238. For rare vs. common homozygotes, odds ratio for obesity was 3.32 (95% confidence interval = 1.08-10.19) for ADRB2rs1800888(Thr164Ile), 1.42 (1.35-1.52) for FTOrs9939609, 1.18 (1.06-1.30) for MC4Rrs17782313, and 1.28 (1.10-1.50) for TMEM18rs6548238 (common vs. rare). Corresponding odds ratios for diabetes were 1.85 (0.24-14.29), 1.22 (1.07-1.39), 0.96 (0.80-1.16), and 1.61 (1.17-2.22), respectively. After adjustment for BMI, only TMEM18rs6548238 remained associated with diabetes. BMI was increased in rare vs. common homozygotes in FTOrs9939609, MC4Rrs17782313, and TMEM18rs6548238 (common vs. rare) but not in ADRB2rs1800888(Thr164Ile).
Our results suggest that ADRB2rs1800888(Thr164Ile) rare vs. common homozygotes are not significantly associated with an increase in BMI measured continuously but may be associated with an increased risk of obesity. Also, TMEM18rs6548238 associated with risk of diabetes after adjustment for BMI. These findings need confirmation in other studies.
PubMed ID
22466342 View in PubMed
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25-hydroxyvitamin D and symptomatic ischemic stroke: an original study and meta-analysis.

https://arctichealth.org/en/permalink/ahliterature118271
Source
Ann Neurol. 2013 Jan;73(1):38-47
Publication Type
Article
Date
Jan-2013
Author
Peter Brøndum-Jacobsen
Børge G Nordestgaard
Peter Schnohr
Marianne Benn
Author Affiliation
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Denmark.
Source
Ann Neurol. 2013 Jan;73(1):38-47
Date
Jan-2013
Language
English
Publication Type
Article
Keywords
Aged
Biological Markers - blood
Brain Ischemia - blood - diagnosis - epidemiology
Denmark - epidemiology
Female
Follow-Up Studies
Humans
Male
Middle Aged
Population Surveillance - methods
Prospective Studies
Risk factors
Stroke - blood - diagnosis - epidemiology
Vitamin D - analogs & derivatives - blood
Abstract
We tested the hypothesis that low plasma concentrations of 25-hydroxyvitamin D are associated with increased risk of symptomatic ischemic stroke in the general population.
We measured plasma 25-hydroxyvitamin D in 10,170 individuals from the general population, the Copenhagen City Heart Study. During 21 years of follow-up, 1,256 and 164 persons developed ischemic and hemorrhagic stroke, respectively. In a meta-analysis of ischemic stroke, we included 10 studies, 58,384 participants, and 2,644 events.
Stepwise decreasing plasma 25-hydroxyvitamin D concentrations were associated with stepwise increasing risk of ischemic stroke both as a function of seasonally adjusted percentile categories and as a function of clinical categories of 25-hydroxyvitamin D (p for trend = 2 × 10(-3)). In a Cox regression model comparing individuals with plasma 25-hydroxyvitamin D concentrations between the 1st and 4th percentiles to individuals with 25-hydroxyvitamin D concentrations between the 50th and 100th percentiles, multivariate adjusted hazard ratio of ischemic stroke was 1.82 (95% confidence interval, 1.41-2.34). Comparing individuals with clinical categories of severe vitamin D deficiency (
PubMed ID
23225498 View in PubMed
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25-hydroxyvitamin d levels and risk of ischemic heart disease, myocardial infarction, and early death: population-based study and meta-analyses of 18 and 17 studies.

https://arctichealth.org/en/permalink/ahliterature121124
Source
Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2794-802
Publication Type
Article
Date
Nov-2012
Author
Peter Brøndum-Jacobsen
Marianne Benn
Gorm B Jensen
Børge G Nordestgaard
Author Affiliation
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
Source
Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2794-802
Date
Nov-2012
Language
English
Publication Type
Article
Keywords
Aged
Biological Markers - blood
Denmark - epidemiology
Female
Follow-Up Studies
Humans
Incidence
Kaplan-Meier Estimate
Male
Middle Aged
Multivariate Analysis
Myocardial Infarction - blood - epidemiology - mortality
Myocardial Ischemia - blood - epidemiology - mortality
Prognosis
Proportional Hazards Models
Prospective Studies
Risk assessment
Risk factors
Time Factors
Vitamin D - analogs & derivatives - blood
Vitamin D Deficiency - blood - diagnosis - epidemiology - mortality
Abstract
We tested the hypothesis that reduced plasma 25-hydroxyvitamin D associates with increased risk of ischemic heart disease, myocardial infarction, and early death.
We measured baseline plasma 25-hydroxyvitamin D in 10 170 women and men from the Danish general population without vitamin D-fortified food. During 29 years of follow-up, 3100 persons developed ischemic heart disease, 1625 myocardial infarction, and 6747 died. Decreasing plasma 25-hydroxyvitamin D levels were associated with increasing risk of ischemic heart disease, myocardial infarction, and early death as a function of seasonally adjusted percentile categories (P for trend, 2×10(-4)-3×10(-53)). Comparing individuals with plasma 25-hydroxyvitamin D levels at the 1st to 4th percentile with individuals with levels at the 50th to 100th percentile, the multivariable adjusted risk was increased by 40% (95% CI, 14%-72%) for ischemic heart disease, by 64% (25%-114%) for myocardial infarction, by 57% (38%-78%) for early death, and by 81% (40%-135%) for fatal ischemic heart disease/myocardial infarction. In the meta-analyses of 18 and 17 studies, risk of ischemic heart disease and early death were increased by 39% (25%-54%) and 46% (31%-64%) for lowest versus highest quartile of 25-hydroxyvitamin D level.
We observed increasing risk of ischemic heart disease, myocardial infarction, and early death with decreasing plasma 25-hydroxyvitamin D levels. These findings were substantiated in meta-analyses.
PubMed ID
22936341 View in PubMed
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164Ile allele in the beta2-Adrenergic receptor gene is associated with risk of elevated blood pressure in women. The Copenhagen City Heart Study.

https://arctichealth.org/en/permalink/ahliterature173671
Source
Pharmacogenet Genomics. 2005 Sep;15(9):633-45
Publication Type
Article
Date
Sep-2005
Author
Amar A Sethi
Anne Tybjaerg-Hansen
Gorm B Jensen
Børge G Nordestgaard
Author Affiliation
Department of Clinical Biochemistry, Herlev University Hospital, Herlev, Denmark.
Source
Pharmacogenet Genomics. 2005 Sep;15(9):633-45
Date
Sep-2005
Language
English
Publication Type
Article
Keywords
Alleles
Arginine - chemistry
Blood pressure
Body mass index
Denmark
Female
Gene Expression Regulation
Gene Frequency
Genetic Variation
Genotype
Glutamic Acid - chemistry
Glutamine - chemistry
Glycine - chemistry
Haplotypes
Heart rate
Heterozygote
Humans
Hypertension - genetics
Isoleucine - chemistry
Linkage Disequilibrium
Male
Receptors, Adrenergic, beta-2 - genetics
Risk
Risk factors
Sequence Analysis, DNA
Sex Factors
Time Factors
Abstract
Since beta2-adrenergic receptors are important regulators of blood pressure, genetic variation in this receptor could explain risk of elevated blood pressure in selected individuals. We tested the hypothesis that Gly16Arg, Gln27Glu, and Thr164Ile in the beta2-adrenergic receptor gene associated with elevated blood pressure.
We genotyped 9185 individuals from the adult Danish general population.
Allele frequencies of 16Arg, 27Glu, and 164Ile were 0.38, 0.44, and 0.01, respectively. Among women never treated with antihypertensive medication those heterozygous for Thr164Ile versus non-carriers had increased diastolic blood pressure (P=0.02). Women heterozygous for Thr164Ile versus non-carriers had an odds ratio for elevated blood pressure of 1.93 (95% CI: 1.30-2.86). Finally, women double heterozygous for Thr164Ile and Gln27Glu or Gly16Arg versus non-carriers at all 3 loci had an odds ratio for elevated blood pressure of 2.49 (1.28-4.85) or 3.19 (1.46-6.97). In men, blood pressure was not influenced by this genetic variation.
In women Thr164Ile heterozygosity is associated with increased diastolic blood pressure, and represent a risk factor for elevated blood pressure in women in the general population. This was most pronounced in those women also heterozygous for Gln27Glu or Gly16Arg.
PubMed ID
16041242 View in PubMed
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The ABCG5/8 cholesterol transporter and myocardial infarction versus gallstone disease.

https://arctichealth.org/en/permalink/ahliterature104661
Source
J Am Coll Cardiol. 2014 May 27;63(20):2121-8
Publication Type
Article
Date
May-27-2014
Author
Stefan Stender
Ruth Frikke-Schmidt
Børge G Nordestgaard
Anne Tybjaerg-Hansen
Author Affiliation
Copenhagen University Hospitals and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
Source
J Am Coll Cardiol. 2014 May 27;63(20):2121-8
Date
May-27-2014
Language
English
Publication Type
Article
Keywords
ATP-Binding Cassette Transporters - blood - genetics
Aged
Denmark - epidemiology
Female
Gallstones - blood - epidemiology - genetics
Genetic Variation
Genotype
Humans
Lipoproteins - blood - genetics
Male
Middle Aged
Myocardial Infarction - blood - epidemiology - genetics
Prevalence
Abstract
The study sought to test the hypothesis that genetic variation in ABCG5/8, the transporter responsible for intestinal and hepatobiliary cholesterol efflux, may simultaneously influence plasma and biliary cholesterol levels, and hence risk of myocardial infarction (MI) and gallstone disease in opposite directions.
High plasma levels of low-density lipoprotein (LDL) cholesterol are a causal risk factor for MI, whereas high levels of biliary cholesterol promote gallstone formation.
A total of 60,239 subjects from Copenhagen were included, including 5,647 with MI and 3,174 with symptomatic gallstone disease. Subjects were genotyped for 6 common, nonsynonymous and functional variants in ABCG5/8, and a combined weighted genotype score was calculated.
Combined, weighted genotype scores were associated with stepwise decreases in LDL cholesterol of up to 5.9% (0.20 mmol/l) for individuals with a score =8.0 (prevalence = 11%) versus
Notes
Comment In: J Am Coll Cardiol. 2014 May 27;63(20):2129-3024657684
PubMed ID
24657701 View in PubMed
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ADH1B and ADH1C genotype, alcohol consumption and biomarkers of liver function: findings from a Mendelian randomization study in 58,313 European origin Danes.

https://arctichealth.org/en/permalink/ahliterature268417
Source
PLoS One. 2014;9(12):e114294
Publication Type
Article
Date
2014
Author
Debbie A Lawlor
Marianne Benn
Luisa Zuccolo
N Maneka G De Silva
Anne Tybjaerg-Hansen
George Davey Smith
Børge G Nordestgaard
Source
PLoS One. 2014;9(12):e114294
Date
2014
Language
English
Publication Type
Article
Keywords
Adult
Aged
Alcohol Dehydrogenase - genetics
Alcohol Drinking - epidemiology - genetics - physiopathology
Denmark - epidemiology
Female
Genetic Variation
Genotype
Humans
Liver - metabolism - physiopathology
Male
Mendelian Randomization Analysis
Middle Aged
Abstract
The effect of alcohol consumption on liver function is difficult to determine because of reporting bias and potential residual confounding. Our aim was to determine this effect using genetic variants to proxy for the unbiased effect of alcohol.
We used variants in ADH1B and ADH1C genes as instrumental variables (IV) to estimate the causal effect of long-term alcohol consumption on alanine aminotransferase (ALT), ?-glutamyl-transferase (?-GT), alkaline phosphatase (ALP), bilirubin and prothrombin action. Analyses were undertaken on 58,313 Danes (mean age 56).
In both confounder adjusted multivariable and genetic-IV analyses greater alcohol consumption, amongst those who drank any alcohol, was associated with higher ALT [mean difference per doubling of alcohol consumption: 3.4% (95% CI: 3.1, 3.7) from multivariable analyses and 3.7% (-4.5, 11.9) from genetic-IV analyses] and ?-GT [8.2% (7.8, 8.5) and 6.8% (-2.8, 16.5)]. The point estimates from the two methods were very similar and statistically the results from the two methods were consistent with each other for effects with ALT and ?-GT (both pdiff>0.3). Results from the multivariable analyses suggested a weak inverse association of alcohol with ALP [-1.5% (-1 .7, -1.3)], which differed from the strong positive effect found in genetic-IV analyses [11.6% (6.8, 16.4)] (p diff
Notes
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PubMed ID
25503943 View in PubMed
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Alcohol intake, myocardial infarction, biochemical risk factors, and alcohol dehydrogenase genotypes.

https://arctichealth.org/en/permalink/ahliterature98530
Source
Circ Cardiovasc Genet. 2009 Oct;2(5):507-14
Publication Type
Article
Date
Oct-2009
Author
Janne S Tolstrup
Morten Grønbaek
Børge G Nordestgaard
Author Affiliation
Center for Alcohol Research, National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark. jst@niph.dk
Source
Circ Cardiovasc Genet. 2009 Oct;2(5):507-14
Date
Oct-2009
Language
English
Publication Type
Article
Keywords
Adult
Aged
Alcohol Dehydrogenase - genetics
Alcohol Drinking - adverse effects
Biological Markers - blood - metabolism
Cholesterol, HDL - blood
Cholesterol, LDL - blood
Denmark - epidemiology
Female
Fibrinogen - metabolism
Follow-Up Studies
Genotype
Humans
Male
Middle Aged
Myocardial Infarction - enzymology - epidemiology - genetics - metabolism
Risk factors
Abstract
BACKGROUND: The risk of myocardial infarction is lower among light-to-moderate alcohol drinkers compared with abstainers. We tested associations between alcohol intake and risk of myocardial infarction and risk factors and whether these associations are modified by variations in alcohol dehydrogenases. METHODS AND RESULTS: We used information on 9584 men and women from the Danish general population in the Copenhagen City Heart Study. During follow-up, from 1991 to 2007, 663 incident cases of myocardial infarction occurred. We observed that increasing alcohol intake was associated with decreasing risk of myocardial infarction, decreasing low-density lipoprotein cholesterol and fibrinogen, increasing diastolic and systolic blood pressure and high-density lipoprotein cholesterol, and with U-shaped nonfasting triglycerides. In contrast, ADH1B and ADH1C genotypes were not associated with risk of myocardial infarction or with any of the cardiovascular biochemical risk factors, and there was no indication that associations between alcohol intake and myocardial infarction and between alcohol intake and risk factors were modified by genotypes. CONCLUSIONS: Increasing alcohol intake is associated with decreasing risk of myocardial infarction, decreasing low-density lipoprotein cholesterol and fibrinogen, increasing diastolic and systolic blood pressure and high-density lipoprotein cholesterol, and U-shaped nonfasting triglycerides. These associations were not modified by ADH1B and ADH1C are genotypes.
PubMed ID
20031627 View in PubMed
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Antihypertensive treatment and risk of atrial fibrillation: a nationwide study.

https://arctichealth.org/en/permalink/ahliterature259079
Source
Eur Heart J. 2014 May;35(18):1205-14
Publication Type
Article
Date
May-2014
Author
Sarah C W Marott
Sune F Nielsen
Marianne Benn
Børge G Nordestgaard
Source
Eur Heart J. 2014 May;35(18):1205-14
Date
May-2014
Language
English
Publication Type
Article
Keywords
Adrenergic beta-Antagonists - therapeutic use
Aged
Angiotensin Receptor Antagonists - therapeutic use
Angiotensin-Converting Enzyme Inhibitors - therapeutic use
Antihypertensive Agents - therapeutic use
Atrial Fibrillation - epidemiology - prevention & control
Calcium Channel Blockers - therapeutic use
Denmark - epidemiology
Diuretics - therapeutic use
Female
Humans
Hypertension - drug therapy - epidemiology
Incidence
Male
Middle Aged
Retrospective Studies
Risk factors
Stroke - epidemiology - prevention & control
Abstract
To examine the associations between antihypertensive treatment with angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs), ß-blockers, diuretics, or calcium-antagonists, and risk of atrial fibrillation. We examined these associations using the entire Danish population from 1995 through 2010.
Excluding medication used in atrial fibrillation, we matched individuals on ACEi monotherapy 1:1 with individuals on ß-blocker (n = 48 658), diuretic (n = 69 630), calcium-antagonist (n = 57 646), and ARB monotherapy (n = 20 158). Likewise, individuals on ARB monotherapy were matched 1:1 with individuals on ß-blocker (n = 20 566), diuretic (n = 20 832), calcium-antagonist (n = 20 232), and ACEi monotherapy (n = 20 158). All were free of atrial fibrillation and of predisposing diseases like heart failure, ischaemic heart disease, diabetes mellitus, and hyperthyroidism at baseline and none received any other antihypertensive medication. We studied risk of atrial fibrillation, and used risk of stroke, influenced by lowering blood pressure rather than renin-angiotensin system blockade per se, as an indicator of the importance of blood pressure lowering per se. Hazard ratios of atrial fibrillation for ACEi and ARB monotherapy were 0.12 (95% CI: 0.10-0.15) and 0.10 (0.07-0.14) compared with ß-blocker, 0.51 (0.44-0.59) and 0.43 (0.32-0.58) compared with diuretic, and 0.97 (0.81-1.16) and 0.78 (0.56-1.08) compared with calcium-antagonist monotherapy. Risk of stroke did not differ among the five antihypertensive medications.
Use of ACEis and ARBs compared with ß-blockers and diuretics associates with a reduced risk of atrial fibrillation, but not stroke, within the limitations of a retrospective study reporting associations. This suggests that controlling activation of the renin-angiotensin system in addition to controlling blood pressure is associated with a reduced risk of atrial fibrillation.
Notes
Comment In: Eur Heart J. 2014 May;35(18):1169-7124566798
PubMed ID
24347316 View in PubMed
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Assessment of coronary calcification using calibrated mass score with two different multidetector computed tomography scanners in the Copenhagen General Population Study.

https://arctichealth.org/en/permalink/ahliterature282425
Source
Eur J Radiol. 2017 Mar;88:21-25
Publication Type
Article
Date
Mar-2017
Author
Andreas Fuchs
Jaap M Groen
Ben A Arnold
Sasho Nikolovski
Andreas D Knudsen
J Tobias Kühl
Børge G Nordestgaard
Marcel J W Greuter
Klaus F Kofoed
Source
Eur J Radiol. 2017 Mar;88:21-25
Date
Mar-2017
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Calcinosis - complications - diagnostic imaging
Calibration
Coronary Artery Disease - complications - diagnostic imaging
Denmark
Female
Humans
Male
Middle Aged
Multidetector Computed Tomography - instrumentation - methods
Phantoms, Imaging
Reproducibility of Results
Tomography Scanners, X-Ray Computed
Abstract
Population studies have shown coronary calcium score to improve risk stratification in subjects suspected for cardiovascular disease. The aim of this work was to assess the validity of multidetector computed tomography (MDCT) for measurement of calibrated mass scores (MS) in a phantom study, and to investigate inter-scanner variability for MS and Agaston score (AS) recorded in a population study on two different high-end MDCT scanners.
A calcium phantom was scanned by a first (A) and second (B) generation 320-MDCT. MS was measured for each calcium deposit from repeated measurements in each scanner and compared to known physical phantom mass. Random samples of human subjects from the Copenhagen General Population Study were scanned with scanner A (N=254) and scanner B (N=253) where MS and AS distributions of these two groups were compared.
The mean total MS of the phantom was 32.9?0.8mg and 33.1?0.9mg (p=0.43) assessed by scanner A and B respectively - the physical calcium mass was 34.0mg. Correlation between measured MS and physical calcium mass was R(2)=0.99 in both scanners. In the population study the median total MS was 16.8mg (interquartile range (IQR): 3.5-81.1) and 15.8mg (IQR: 3.8-63.4) in scanner A and B (p=0.88). The corresponding median total AS were 92 (IQR: 23-471) and 89 (IQR: 40-384) (p=0.64).
Calibrated calcium mass score may be assessed with very high accuracy in a calcium phantom by different generations of 320-MDCT scanners. In population studies, it appears acceptable to pool calcium scores acquired on different 320-MDCT scanners.
PubMed ID
28189204 View in PubMed
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Association of clinical benign prostate hyperplasia with prostate cancer incidence and mortality revisited: a nationwide cohort study of 3,009,258 men.

https://arctichealth.org/en/permalink/ahliterature133435
Source
Eur Urol. 2011 Oct;60(4):691-8
Publication Type
Article
Date
Oct-2011
Author
David D Ørsted
Stig E Bojesen
Sune F Nielsen
Børge G Nordestgaard
Author Affiliation
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark.
Source
Eur Urol. 2011 Oct;60(4):691-8
Date
Oct-2011
Language
English
Publication Type
Article
Keywords
5-alpha Reductase Inhibitors - therapeutic use
Adrenergic alpha-Antagonists - therapeutic use
Adult
Aged
Aged, 80 and over
Cohort Studies
Denmark - epidemiology
Humans
Incidence
Male
Middle Aged
Prostate - drug effects - surgery
Prostatectomy - statistics & numerical data
Prostatic Hyperplasia - drug therapy - mortality - surgery
Prostatic Neoplasms - drug therapy - mortality - surgery
Registries - statistics & numerical data
Treatment Outcome
Abstract
Although benign prostate hyperplasia (BPH) and prostate cancer (PCa) share features such as hormone-dependent growth and response to treatment with antiandrogen therapy, BPH is generally not considered a premalignant lesion.
To determine whether clinical BPH is associated with an increased risk of PCa incidence and mortality.
Using designs with individual participant data from five national registries, we studied the entire Danish male population from 1980 through 2006, a total of 3,009,258 Danish men. We collected PCa diagnoses (n=53,315), information on PCa mortality (n=25,459), and ascertained clinical BPH (not histologically proven BPH) through hospitalization (n=187,591) and/or surgery (n=77,698) from 1980 to 2006 and the use of a-adrenergic receptor antagonists (n=143,365) and/or the use of 5a-reductase inhibitors (5-ARIs) (n=47,465) from 1995 to 2006.
PCa incidence and mortality was assessed for each category of clinical BPH using Kaplan-Meier plots of cumulative incidence and Cox proportional hazard ratios (HRs) adjusted for potential confounders.
For the entire cohort studies, multivariate-adjusted HRs for PCa incidence were 2.22 (95% confidence interval, 2.13-2.31) in men hospitalized and 3.26 (3.03-3.50) in men operated on for clinical BPH versus general population controls. Corresponding HRs for PCa mortality were 2.00 (1.91-2.08) for hospitalization and 7.85 (7.40-8.32) for surgery. For age-matched cohort studies, corresponding HRs for PCa incidence were 3.04 (2.96-3.13) for hospitalization, 2.60 (2.47-2.73) for surgery, 4.49 (4.33-4.65) for a-adrenergic receptor antagonist use, and 2.54 (2.40-2.68) for 5-ARI use. Each category of clinical BPH has limitations, but limitations differ between the categories and therefore are unlikely to explain the results.
In Danish men followed for up to 27 yr, clinical BPH was associated with a two- to three-fold increased risk of PCa incidence and with a two- to eight-fold increased risk of PCa mortality. These data should not be used to infer causality.
Notes
Comment In: J Urol. 2012 Sep;188(3):89822883790
Comment In: J Urol. 2012 Jan;187(1):14222153426
Comment In: Eur Urol. 2011 Oct;60(4):699-700; discussion 701-221802829
PubMed ID
21705134 View in PubMed
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156 records – page 1 of 16.