lunes, 5 de agosto de 2013

A Genetic Score Can Identify Men at High Risk for P... [Eur Urol. 2013] - PubMed - NCBI

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.

Nordström T, Aly M, Eklund M, Egevad L, Grönberg H.

Source

Department of Clinical Sciences at Danderyds Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Abstract

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.