A Genetic Score Can Identify Men at High Risk for Prostate Cancer Among Men With Prostate-Specific Antigen of 1-3 ng/ml
Menée auprès d'une cohorte de 2 696 hommes âgés de 50 à 69 ans et dont le niveau du PSA est compris entre 1 et 3 ng/ml, puis menée à partir de biopsies prélevées sur 172 d'entre eux, cette étude montre qu'un système de score, reposant sur la présence de 49 polymorphismes à simple nucléotide, peut permettre d'identifier les patients présentant un risque élevé de cancer de la prostate et devant subir une biospie
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, 840 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.
Take Home Message : A genetic score based on single nucleotide polymorphisms can be used in men with prostate-specific antigen of 1–3 ng/ml to identify those at higher risk for prostate cancer.
European urology , résumé, 2012