PD56-07 STATISTICAL EVIDENCE FOR GUIDELINE-RECOMMENDED GENES FOR PREDICTING PROSTATE CANCER RISK IN A LARGE POPULATION-BASED COHORT

Abstract

You have accessJournal of UrologyProstate Cancer: Detection & Screening VI (PD56)1 Sep 2021PD56-07 STATISTICAL EVIDENCE FOR GUIDELINE-RECOMMENDED GENES FOR PREDICTING PROSTATE CANCER RISK IN A LARGE POPULATION-BASED COHORT Jun Wei, Wancai Yang, Zhuqing Shi, W. Kyle Resurreccion, Yasin Bhanji, Christian Pavlovich, S. Lilly Zheng, Kathleen Cooney, William Isaacs, Brian Helfand, Jim Lu, and Jianfeng Xu Jun WeiJun Wei More articles by this author , Wancai YangWancai Yang More articles by this author , Zhuqing ShiZhuqing Shi More articles by this author , W. Kyle ResurreccionW. Kyle Resurreccion More articles by this author , Yasin BhanjiYasin Bhanji More articles by this author , Christian PavlovichChristian Pavlovich More articles by this author , S. Lilly ZhengS. Lilly Zheng More articles by this author , Kathleen CooneyKathleen Cooney More articles by this author , William IsaacsWilliam Isaacs More articles by this author , Brian HelfandBrian Helfand More articles by this author , Jim LuJim Lu More articles by this author , and Jianfeng XuJianfeng Xu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002090.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Germline testing for prostate cancer (PCa) is now recommended by clinical guidelines for PCa risk assessment. Ten genes involved in hereditary cancer syndromes (ATM, BRCA1, BRCA2, CHEK2, MLH1, MSH2, MSH6, PALB2, PMS2 and RAD51D) and HOXB13 have been recommended. However, their roles in predicting PCa risk are inconsistent among studies, largely due to low mutation frequencies and small sample sizes in individual studies. The objective of this study is to systematically evaluate statistical evidence for these genes for predicting PCa risk in a large population-based cohort. METHODS: A total of 84,270 Caucasian men with whole exome sequencing data from the UK Biobank (UKB) were included, including 4,197 and 80,073 men with and without a PCa diagnosis at recruitment or during follow-up, respectively. Pathogenic/likely pathogenic (P/LP) variants were annotated using a recommended five-tier variant classification protocol. Association tests were performed using the Fisher’s exact test (due to rarity of mutation carriers) and logistic regression model adjusting for genetic background ( top 10 genetic principal components). RESULTS: Among 11 guideline recommended genes and NBN, significantly higher P/LP mutation carrier rates in PCa cases than controls were found for 4 genes at P<0.05 (Fisher’s exact test): odds ratio (95%) for PCa risk was 4.23 (3.11-5.68) for HOXB13, 2.62 (1.82-3.67) for BRCA2, 2.45 (1.71-3.44) for ATM, and 1.71 (1.3-2.23) for CHEK2 (Table 1). No significant difference was found for the remaining 8 genes, P>0.05. Similar findings were obtained after adjusting for genetic background. However, it is noted that mutation carriers in each gene did not have significantly different age at diagnosis than non-carriers (Table 2). CONCLUSIONS: In this first systematic evaluation of statistical evidence for guideline-recommended genes in predicting PCa risk from a population-based cohort, only four genes were implicated. Caution needs to be exercised when interpreting results from germline testing. Source of Funding: This study was partially supported by grants from Department of Defense (W81XWH-16-1-0764, W81XWH-16-1-0765, and W81XWH-16-1-0766) and GoPath Laboratories LLC © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1006-e1006 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jun Wei More articles by this author Wancai Yang More articles by this author Zhuqing Shi More articles by this author W. Kyle Resurreccion More articles by this author Yasin Bhanji More articles by this author Christian Pavlovich More articles by this author S. Lilly Zheng More articles by this author Kathleen Cooney More articles by this author William Isaacs More articles by this author Brian Helfand More articles by this author Jim Lu More articles by this author Jianfeng Xu More articles by this author Expand All Advertisement Loading ...