Eur Urol. 2013 Jul 19. pii: S0302-2838(13)00720-3. doi: 10.1016/j.eururo.2013.07.005. [Epub ahead of print]
A Genetic Score Can Identify Men at High Risk for Prostate Cancer Among Men With Prostate-Specific Antigen of 1-3 ng/ml.
SourceDepartment of Clinical Sciences at Danderyds Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
BACKGROUND:The diagnostic performance of a genetic score based on single nucleotide polymorphisms (SNPs) is unknown in the prostate-specific antigen (PSA) range of 1-3 ng/ml. A substantial proportion of men in this PSA span have prostate cancer (PCa), but biomarkers to determine who should undergo a prostate biopsy are lacking.
OBJECTIVE:To evaluate whether a genetic risk score identifies men in the PSA range of 1-3 ng/ml who are at higher risk for PCa.
DESIGN, SETTING, AND PARTICIPANTS:Men aged 50-69 yr with PSA 1-3 ng/ml and without a previous prostate biopsy were selected from the STHLM2 cohort. Of 2696 men, 49 SNPs were genotyped, and a polygenic risk score was calculated. Of these men, 860 were invited according to risk score, and 172 underwent biopsy.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The risk of PCa was assessed using univariate and multivariate logistic regression analysis.
RESULTS AND LIMITATIONS:PCa was diagnosed in 47 of 172 participants (27%), with Gleason sum 6 in 36 of 47 men (77%) and Gleason sum ≥7 in 10 of 47 men (21%); one man had intraductal cancer. The genetic score was a significant predictor of a positive biopsy (p=0.028), even after adjusting for PSA, ratio of free to total PSA, prostate volume, age, and family history. There was an increase in the odds ratio of 1.60 (95% confidence interval, 1.05-2.45) with increasing genetic risk score. The absolute risk difference of positive biopsy was 19 percentage points, comparing the high and low genetic risk group (37% vs 18%).
CONCLUSIONS:A risk score based on SNPs predicts biopsy outcome in previously unbiopsied men with PSA 1-3 ng/ml. Introducing a genetic-based risk stratification tool can increase the proportion of men being classified in line with their true risk of PCa.
Copyright © 2013. Published by Elsevier B.V.
KEYWORDS:Cancer, Genetic risk, PSA, Prostate, Risk stratification, SNP
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