MP69-12 ADDED VALUE OF GENETIC RISK SCORE TO THE PROSTATE CANCER PREVENTION TRIAL (PCPT) RISK CALCULATOR: FINDINGS FROM THE PCPT STUDY

Abstract

You have accessJournal of UrologyProstate Cancer: Detection & Screening V1 Apr 2014MP69-12 ADDED VALUE OF GENETIC RISK SCORE TO THE PROSTATE CANCER PREVENTION TRIAL (PCPT) RISK CALCULATOR: FINDINGS FROM THE PCPT STUDY Haitao Chen, Jielin Sun, Donna Ankerst, Robin Leach, Phyllis Goodman, Scott Lucia, Catherine Tangen, William Isaacs, S. Lilly Zheng, Ian Thompson, Elizabeth Platz, and Jianfeng Xu Haitao ChenHaitao Chen More articles by this author , Jielin SunJielin Sun More articles by this author , Donna AnkerstDonna Ankerst More articles by this author , Robin LeachRobin Leach More articles by this author , Phyllis GoodmanPhyllis Goodman More articles by this author , Scott LuciaScott Lucia More articles by this author , Catherine TangenCatherine Tangen More articles by this author , William IsaacsWilliam Isaacs More articles by this author , S. Lilly ZhengS. Lilly Zheng More articles by this author , Ian ThompsonIan Thompson More articles by this author , Elizabeth PlatzElizabeth Platz More articles by this author , and Jianfeng XuJianfeng Xu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2231AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To determine whether a genetic risk score (GRS) derived from multiple prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) provided added value to the Prostate Cancer Prevention Trial (PCPT) risk calculator in discriminating biopsy outcomes. METHODS We calculated PCa risk score using the PCPT calculator for men in the PCPT placebo arm and classified them into three risk groups based on its quartile (Q): low (Q1), intermediate (Q2-Q3), and high (Q4). We also calculated GRS based on 24 PCa risk-associated SNPs identified through genome-wide association studies for each Caucasian man whose DNA sample was available (N=4,528). Because GRS of 1.0 by definition represents an average inherited risk in the general population, men were classified as low, intermediate, and high inherited risk group if their GRS <0.5, 0.5-1.5, and >1.5, respectively. High-grade PCa was defined as Gleason score >=7. RESULTS The median GRS was significantly higher in men with a positive biopsy (1.14) than negative biopsy (0.97), P=3.24x10-19. When both the PCPT risk score and GRS were included in a multiple logistic regression model, GRS remained significantly associated with PCa (P=1.10x10-16) and high-grade PCa (P=0.03). When not considering GRS, the difference in the PCa detection rate between men in the low (11.8%) and high (41.8%) PCPT risk groups was 29.9% (Table). When GRS was added to the PCPT risk calculator, the difference in the PCa detection rate between the lowest (4% in low PCPT score and low GRS) and highest (49.2% in high PCPT score and high GRS) groups was 45.2%. The added value of GRS was also found within each PCPT risk group. For example, for men in the intermediate PCPT risk group, the PCa detection rate differed widely, from 13.2%, 25.6% to 31.7% if they had a low, intermediate or high GRS, respectively, Ptrend=1.02x10-7. A similar but not statistically significant trend was found for high-grade PCa in the low and intermediate PCPT risk groups. A new PCPT score incorporating GRS (PCPT-G) was developed. CONCLUSIONS GRS is independently associated with PCa and high-grade PCa. It provides an added value to the PCPT risk calculator for better discriminating biopsy outcomes. Table. Added value of genetic risk score (GRS) derived from 24 SNPs to the PCPT risk calculator in the placebo arm of the PCPT study Risk based on PCPT calculator All subjects Low (GRS < 0.5) Mid (GRS=0.5-1.5) High (GRS >1.5) P-trend # (%) of subjects # (%) of subjects # (%) of subjects Low (Q1), N=1,064 175 (16.4%) 738 (69.4%) 151 (14.3%) Mid (Q2-Q3), N=2,130 303 (14.3%) 1502 (70.5%) 325 (15.3%) High (Q4), N=1,063 125 (11.8%) 753 (70.8%) 185 (17.4%) Detection rate of any prostate cancer, Mean (95% CI) Detection rate of any prostate cancer, Mean (95% CI) Detection rate of any prostate cancer, Mean (95% CI) Low (Q1), N=1,064 11.8 (9.9-13.8) 4.0 (1.1-6.9) 12.9 (10.5-15.3) 15.9 (10.1-21.7) 7.00E-04 Mid (Q2-Q3), N=2,130 24.7 (22.9-26.6) 13.2 (9.4-17.0) 25.6 (23.4-27.8) 31.7 (26.6-36.8) 1.02E-07 High (Q4), N=1,063 41.8 (38.1-44.7) 35.2 (26.8-43.6) 41.0 (37.5-44.6) 49.2 (42.0-56.4) 1.11E-02 Detection rate of high-grade prostate cancer, Mean (95% CI) Detection rate of high-grade prostate cancer, Mean (95% CI) Detection rate of high-grade prostate cancer, Mean (95% CI) Low (Q1), N=1,064 1.7 (0.9-2.5) 0.6 (-0.5-1.7) 1.9 (0.9-2.9) 2.0 (-0.2-4.2) 2.98E-01 Mid (Q2-Q3), N=2,130 4.0 (3.2-4.8) 3.0 (1.1-5.0) 3.8 (2.8-4.8) 5.8 (3.3-8.3) 7.32E-02 High (Q4), N=1,063 10.7 (8.9-12.6) 7.0 (2.6-11.5) 11.9 (9.6-14.2) 8.3 (4.3-12.3) 9.52E-01 Q stands for Quartile; high-grade prostate cancer is defined as Gleason score 4+3 or worse © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e819 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Haitao Chen More articles by this author Jielin Sun More articles by this author Donna Ankerst More articles by this author Robin Leach More articles by this author Phyllis Goodman More articles by this author Scott Lucia More articles by this author Catherine Tangen More articles by this author William Isaacs More articles by this author S. Lilly Zheng More articles by this author Ian Thompson More articles by this author Elizabeth Platz More articles by this author Jianfeng Xu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...