Tobias Nordström1, Markus Aly2, Martin Eklund3, Lars Egevad4, Henrik Grönberg3. 1. Department of Clinical Sciences at Danderyds Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 2. Department of Clinical Sciences at Danderyds Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Electronic address: markus.aly@ki.se. 3. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 4. Department of Oncology-Pathology, 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.
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.
Authors: Stacy Loeb; Sarah B Peskoe; Corinne E Joshu; Wen-Yi Huang; Richard B Hayes; H Ballentine Carter; William B Isaacs; Elizabeth A Platz Journal: Cancer Epidemiol Biomarkers Prev Date: 2014-10-23 Impact factor: 4.254
Authors: Jan Chandra Engel; Thorgerdur Palsdottir; Donna Ankerst; Sebastiaan Remmers; Ashkan Mortezavi; Venkatesh Chellappa; Lars Egevad; Henrik Grönberg; Martin Eklund; Tobias Nordström Journal: Eur Urol Open Sci Date: 2022-05-19
Authors: Elena Castro; Christos Mikropoulos; Elizabeth K Bancroft; Tokhir Dadaev; Chee Goh; Natalie Taylor; Edward Saunders; Nigel Borley; Diana Keating; Elizabeth C Page; Sibel Saya; Stephen Hazell; Naomi Livni; Nandita deSouza; David Neal; Freddie C Hamdy; Pardeep Kumar; Antonis C Antoniou; Zsofia Kote-Jarai; Rosalind A Eeles Journal: Oncologist Date: 2016-05-05