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Eur Urol. 2011 Jul;60(1):21-8. doi: 10.1016/j.eururo.2011.01.017. Epub 2011 Jan 18.

Polygenic risk score improves prostate cancer risk prediction: results from the Stockholm-1 cohort study.

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1
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.

Abstract

BACKGROUND:

More than 1 million prostate biopsies are conducted yearly in the United States. The low specificity of prostate-specific antigen (PSA) results in diagnostic biopsies in men without prostate cancer (PCa). Additional information, such as genetic markers, could be used to avoid unnecessary biopsies.

OBJECTIVE:

To determine whether single nucleotide polymorphisms (SNPs) associated with PCa can be used to determine whether biopsy of the prostate is necessary.

DESIGN, SETTINGS, AND PARTICIPANTS:

The Stockholm-1 cohort (n = 5241) consisted of men who underwent a prostate biopsy during 2005 to 2007. PSA levels were retrieved from databases and family histories were obtained using a questionnaire. Thirty-five validated SNPs were analysed and converted into a genetic risk score that was implemented in a risk-prediction model.

RESULTS AND LIMITATIONS:

When comparing the nongenetic model (based on age, PSA, free-to-total PSA, and family history) with the genetic model and using a fixed number of detected PCa cases, it was found that the genetic model required significantly fewer biopsies than the nongenetic model, with 480 biopsies (22.7%) avoided, at a cost of missing a PCa diagnosis in 3% of patients characterised as having an aggressive disease. However, the overall genetic model does not discriminate between aggressive and nonaggressive cases.

CONCLUSION:

Although the genetic model reduced the number of biopsies more than the nongenetic model, the clinical significance of this finding requires further evaluation.

PMID:
21295399
PMCID:
PMC4417350
DOI:
10.1016/j.eururo.2011.01.017
[Indexed for MEDLINE]
Free PMC Article
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