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The Metabolic Syndrome and the Risk of Prostate Cancer under Competing Risks of Death from Other Causes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2010 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, no 8, 2088-2096 p.Article in journal (Refereed) Published
Abstract [en]


Associations between metabolic syndrome (MetS) components and prostate cancer development have not been studied comprehensively; results have been divergent. Using the National Cholesterol Education Program Adult Treatment panel III (NCEP) and International Diabetes Federation (IDF) definitions of the MetS, we investigated such associations taking competing risks of death into consideration.


In the prospective Uppsala Longitudinal Study of Adult Men of 2,322 Caucasian men with 34 years of follow-up baseline, MetS measurements at age 50 years were used. Cumulative incidence of prostate cancer and death with/without the MetS were calculated. Competing risk of dying was taken into account by calculating the conditional probability of prostate cancer with/without the MetS.


Two hundred and thirty-seven prostate cancers were identified. Prostate cancer probability by age 80 years with baseline MetS compared with without MetS was nonsignificantly higher [5.2 percent units (confidence interval (CI), -0.8% to 11.3%; NCEP); 2.7 percent units (CI, -2.7% to 8.0%; IDF)]; cumulative incidence proportions of death was significantly higher [19.3 percent units (CI, 13.4-25.3%; NCEP); 15.3 percent units (CI, 9.5-21.1%; IDF)]; and conditional probability of prostate cancer considering death from other causes was significantly higher [7.3 percent-units (CI, 0.2-14.5%); odds ratio of 1.64 (CI, 1.03-2.23; NCEP)] and nonsignificantly higher [5.0 percent-units (CI, -1.6% to 11.6%); odds ratio of 1.43 (CI, 0.89-1.90; IDF].


The MetS by the NCEP definition is associated with prostate cancer, taking the competing risk of early death from other causes into account. Impact: The results further highlight the public health effect of the increasing prevalence of MetS and the importance of considering competing risks when studying risk factors for cancer.

Place, publisher, year, edition, pages
2010. Vol. 19, no 8, 2088-2096 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-135608DOI: 10.1158/1055-9965.EPI-10-0112ISI: 000280675000023PubMedID: 20647401OAI: oai:DiVA.org:uu-135608DiVA: diva2:375280
Available from: 2010-12-07 Created: 2010-12-07 Last updated: 2013-04-02Bibliographically approved
In thesis
1. Prostate Cancer; Metabolic Risk Factors, Drug Utilisation, Adverse Drug Reactions
Open this publication in new window or tab >>Prostate Cancer; Metabolic Risk Factors, Drug Utilisation, Adverse Drug Reactions
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Increased possibilities during the last decades for early detection of prostate cancer have sparked research on preventable or treatable risk factors and on improvements in therapy. Treatments of the disease still entail significant side effects potentially affecting men during the rest of their lives. The studies of the present thesis concern different aspects of prostate cancer from etiological risk factors and factors influencing treatment to an improved methodology for the detection of treatment side effects.

Papers I, II, both based in the population based cohort ULSAM (Uppsala Longitudinal Study of Adult Men), investigate possible risk factors of prostate cancer with options for intervention: selenium levels and the metabolic syndrome. The phenomenon of competing risk of death from other causes than prostate cancer and its impact on and importance for choice of statistical methods is also exemplified and discussed for the first time in prostate cancer research.

-Smokers with low selenium status have an increased future risk of later development of prostate cancer. Influence of genetic variability appears plausible.

-The metabolic syndrome and especially its increased waist circumference component are associated with later development of prostate cancer – taking competing risks of death from other causes into account.

Papers III and IV using pharmacoepidemiological methods investigate aspects of drug utilisation in prostate cancer using nationwide and international databases. In Paper III factors influencing anti-androgen use in prostate cancer are investigated, both from a prescriber- and patient perspective.  The age and disease risk group of the patient, unsupported scientifically, influence both the prescribers’ choice of dose and the patients’ adherence to treatment.

-Adherence, not previously investigated in male cancer patients, was considerably higher than reported for adjuvant breast cancer treatment. Subgroups of men suitable for intervention to increase adherence were identified.

Paper IV, investigates the feasibility of improving an established method for screening large adverse drug reactions databases, the proportional reporting ratio (PRR), this by using restricted sub-databases according to treatment area (TA), introducing the concept of PRR-TA.

-The PRR-TA method increases the signal-noise relationship of analyses; a finding highly relevant for possibly conserving manual resources in Pharmacovigilance work in a drug-authority setting.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 115 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 870
Prostate cancer, Epidemiology, Pharmacoepidemiology, Metabolic Syndrome, Selenium, Smoking, hOGG1, MnSOD, Competing Risk, Adherence, Persistance, Medical Possession Ratio, MPR, Signal Detection, PRR, proportional reporting ratio, ULSAM, PcBaSE, EudraVigilance, SPDR, Swedish Prescribe Drug Registry, NPCR, National Prostate Cancer Registry, SDR, Signal, disproportionality analysis, PRR-TA, EudraVigilance
National Category
Research subject
Epidemiology; Urology; Oncology; Geriatrics
urn:nbn:se:uu:diva-194297 (URN)978-91-554-8609-9 (ISBN)
Public defence
2013-04-25, Universitetshuset, Biskopsgatan 3, Uppsala, 09:00 (Swedish)
Available from: 2013-03-26 Created: 2013-02-12 Last updated: 2013-06-27

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Grundmark, BirgittaGarmo, HansBusch, ChristerHolmberg, LarsZethelius, Björn
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