EURURO Vol. 71 No. 5

740 844

Platinum Priority – Prostate Cancer
Editorial by Declan G. Murphy, Gail P. Risbridger, Robert G. Bristow and Shahneen Sandhu on pp. 748–749 of this issue
Germline Mutations in ATM and BRCA1/2 Distinguish Risk
for Lethal and Indolent Prostate Cancer and are Associated
with Early Age at Death
Rong Na y, S. Lilly Zheng , Misop Han y, Hongjie Yu Deke Jiang Sameep Shah
Charles M. Ewing Liti Zhang Kristian Novakovic [5_TD$DIFF] Jacqueline Petkewicz [5_TD$DIFF]
Kamalakar Gulukota Donald L. Helseth Jr Margo Quinn Elizabeth Humphries
Kathleen E. Wiley [6_TD$DIFF] Sarah[7_TD$DIFF] D. Isaacs Yishuo Wu Xu Liu Ning Zhang Chi-Hsiung Wang
Janardan Khandekar Peter J. Hulick Daniel H. Shevrin Kathleen A. Cooney Zhoujun Shen
Alan W. Partin [8_TD$DIFF] H[1_TD$DIFF].[9_TD$DIFF] Ballentine Carter Michael A. Carducci [10_TD$DIFF] Mario[11_TD$DIFF] A. Eisenberger
Sam R. Denmeade [12_TD$DIFF] Michael McGuire Patrick C. Walsh Brian T. Helfand
Charles B. Brendler Qiang Ding Jianfeng Xu William B. Isaacs
a Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China; bProgram for Isaacs Personalized Cancer Care, IL, USA; c Department of
Surgery, NorthShore University HealthSystem, Evanston, IL, USA; dDepartment of Urology and the James Buchanan Brady Urologic Institute, Johns Hopkins
University School of Medicine, Baltimore, MD, USA; e State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China;
f Department of Medicine, NorthShore University HealthSystem, Evanston, IL, USA; g Department of Center for Molecular Medicine, NorthShore University
HealthSystem, Evanston, Illinois, USA; hDepartment of Internal Medicine, University of Utah, Salt Lake City, UT, USA; i Sidney Kimmel Comprehensive Cancer
Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA
available at
journal homepage:
Article info
Article history:
Accepted November 24, 2016
Associate Editor:
James Catto
Keywords:
Lethal prostate cancer
Germline
Mutation
DNA repair genes
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Abstract
Background: Germline mutations in BRCA1/2 and ATM have been associated with
prostate cancer (PCa) risk.
Objective: To directly assess whether germline mutations in these three genes distin-
guish lethal from indolent PCa and whether they confer any effect on age at death.
Design, setting, and participants: A retrospective case-case study of 313 patients who
died of PCa and 486 patients with low-risk localized PCa of European, African, and
Chinese descent. Germline DNA of each of the 799 patients was sequenced for these
three genes.
Outcome measurements and statistical analysis: Mutation carrier rates and their effect
on lethal PCa were analyzed using the Fisher’s exact test and Cox regression analysis,
respectively.
Results and limitations: The combined BRCA1/2 and ATM mutation carrier rate was
significantly higher in lethal PCa patients (6.07%) than localized PCa patients (1.44%),
p = 0.0007. The rate also differed significantly among lethal PCa patients as a function
of age at death (10.00%, 9.08%, 8.33%, 4.94%, and 2.97% in patients who died 60 yr,
61–65 yr, 66–70 yr, 71–75 yr, and over 75 yr, respectively, p = 0.046) and time to death
y These authors contribute equally to the study.
* Corresponding authors. 1001 University Place, Evanston, IL 60201, USA. Tel.+1 (224) 264-7501;
Fax: +1 (224) 364-7675 (J. Xu); 115 Marburg, Johns Hopkins Hospital, 600 North Wolfe Street,
Baltimore, MD 21187, USA. Tel. +1 (410)-955-2518; Fax: +1 (410)-955-2520 (W.B. Isaacs);
12 Mid-Wulumuqi Road, Shanghai 200040, China. Tel. +86-21-52888228 (Q. Ding).
E-mail addresses: (Q. Ding), (J. Xu),
(W.B. Isaacs).
0302-2838/# 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.