umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Combining 33 genetic variants with prostate-specific antigen for prediction of prostate cancer: longitudinal study
International Agency for Research on Cancer (IARC-WHO), Lyon, France.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Show others and affiliations
2012 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 130, no 1, 129-137 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to investigate if a genetic risk score including 33 common genetic variants improves prediction of prostate cancer when added to measures of prostate-specific antigen (PSA). We conducted a case-control study nested within the Northern Sweden Health and Disease Cohort (NSHDC), a prospective cohort in northern Sweden. A total of 520 cases and 988 controls matched for age, and date of blood draw were identified by linkage between the regional cancer register and the NSHDC. Receiver operating characteristic curves with area under curve (AUC) estimates were used as measures of prostate cancer prediction. The AUC for the genetic risk score was 64.3% [95% confidence interval (CI) = 61.4-67.2], and the AUC for total PSA and the ratio of free to total PSA was 86.2% (95% CI = 84.4-88.1). A model including the genetic risk score, total PSA and the ratio of free to total PSA increased the AUC to 87.2% (95% CI = 85.4-89.0, p difference = 0.002). The addition of a genetic risk score to PSA resulted in a marginal improvement in prostate cancer prediction that would not seem useful for clinical risk assessment.

Place, publisher, year, edition, pages
2012. Vol. 130, no 1, 129-137 p.
Keyword [en]
early detection, prostate cancer, prostate-specific antigen, single-nucleotide polymorphism
National Category
Urology and Nephrology
Research subject
Urology
Identifiers
URN: urn:nbn:se:umu:diva-43005DOI: 10.1002/ijc.25986ISI: 000297851300014PubMedID: 21328341OAI: oai:DiVA.org:umu-43005DiVA: diva2:411081
Available from: 2011-04-15 Created: 2011-04-15 Last updated: 2016-03-07Bibliographically approved
In thesis
1. Early diagnosis and treatment of prostate cancer: observational studies in the National Prostate Cancer Register of Sweden and the Västerbotten Intervention Project
Open this publication in new window or tab >>Early diagnosis and treatment of prostate cancer: observational studies in the National Prostate Cancer Register of Sweden and the Västerbotten Intervention Project
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Tidig diagnostik och behandling av prostatacancer  : observationsstudier i Nationella Prostatacancerregistret och Västerbottens interventionsprojekt
Abstract [en]

Prostate-specific antigen (PSA) testing has caused a steep increase in the incidence of prostate cancer, especially the incidence of localised low risk disease. In order to decrease the overdiagnosis accompanied by PSA testing, analysis of inherited genetic variants have been suggested as potential tools for clinical assessment of disease risk. With the aim of minimizing overtreatment and postpone side-effects of curative treatment for low risk prostate cancer, active surveillance, a treatment strategy with initial surveillance and deferred radical prostatectomy at the time of progression has evolved. 

The aim of this thesis was to study the validity of PSA (paper I) and inherited genetic variants (paper II) for early diagnosis of prostate cancer, to assess the extent of PSA testing in Sweden (paper III), and to study the safety of deferred radical prostatectomy in localised low to intermediate risk prostate cancer (paper IV).

The study designs were i) case-control studies nested within the Västerbotten intervention project (paper I and II), ii) observational study in the Cancer Register of Sweden (paper III), and iii) observational study in the NPCR Follow-up study (paper IV).

PSA had a high validity in predicting a prostate cancer diagnosis with an area under the receiver operating characteristics (ROC) curve of 0.86 (95% CI, 0.84 to 0.88). A combined test, including PSA, the ratio of free to total PSA, and 33 single nucleotide polymorphisms (SNPs) in a genetic risk score, increased the area under curve to 0.87 (95% CI, 0.85 to 0.89). The estimated uptake of PSA testing among men aged 55 to 69 years increased from zero to 56% between 1997 and 2007 and there were large variations in the uptake of PSA testing between counties in Sweden. After a median follow-up time of eight years there was no significant difference in presence of any one or more adverse pathology features or prostate cancer specific mortality after primary compared to deferred radical prostatectomy in localised low to intermediate risk prostate cancer.

Results from these studies indicate that PSA and the hitherto identified SNPs are not suitable biomarkers in single-test prostate cancer screening. It is possible to estimate the uptake of PSA testing on a population level. Initial surveillance and deferred radical prostatectomy represent a feasible treatment strategy in localised low to intermediate risk prostate cancer.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2011. 58 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1397
Keyword
Prostate cancer, prostate-specific antigen, single nucleotide polymorphism
National Category
Urology and Nephrology
Research subject
Urology
Identifiers
urn:nbn:se:umu:diva-42843 (URN)978-91-7459-134-7 (ISBN)
Public defence
2011-05-13, Sal E04, Byggnad 6E, Norrlands universitetssjukhus, Umeå, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2011-04-21 Created: 2011-04-14 Last updated: 2011-04-21Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Johansson, MattiasHolmström, BennyBergh, AndersHallmans, GöranStattin, Pär

Search in DiVA

By author/editor
Johansson, MattiasHolmström, BennyBergh, AndersHallmans, GöranStattin, Pär
By organisation
Urology and AndrologyPathologyNutritional Research
In the same journal
International Journal of Cancer
Urology and Nephrology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 130 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf