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Title: A genome-wide pleiotropy scan for prostate cancer risk
Authors: Panagiotou, Orestis A. 
Travis, Ruth C. 
Campa, Daniele 
Berndt, Sonja I. 
Lindstrom, Sara 
Kraft, Peter 
Schumacher, Fredrick R. 
Siddiq, Afshan 
Papatheodorou, Stefania 
Stanford, Janet L. 
Albanes, Demetrius 
Virtamo, Jarmo R K 
Weinstein, Stephanie J. 
Diver, William Ryan 
Gapstur, Susan M. 
Stevens, Victoria L. 
Boeing, Heiner 
Bueno-de-Mesquita, H. Bas 
Barricarte Gurrea, Aurelio 
Kaaks, Rudolf J. 
Khaw, Kay Tee 
Krogh, Vittorio 
Overvad, Kim 
Riboli, Elio B. 
Trichopoulos, Dimitrios V. 
Giovannucci, Edward L. 
Stampfer, Meir J. 
Haiman, Christopher A. 
Henderson, Brian 
Le Marchand, Loic 
Gaziano, John Michael 
Hunter, David John 
Koutros, Stella 
Yeager, Meredith 
Hoover, Robert N. 
Chanock, Stephen J. 
Wacholder, Sholom 
Key, Timothy J. 
Tsilidis, Konstantinos K. 
Major Field of Science: Medical and Health Sciences
Field Category: Clinical Medicine
Keywords: Aggressive prostate cancer;Genome-wide association study;Glycine;Pleiotropy;Single-nucleotide polymorphism
Issue Date: 1-Apr-2015
Source: European Urology, 2015, Volume 67, Issue 4, Pages 649-657
Abstract: Background No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS). Objective To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer. Design, setting, and participants SNPs implicated in any phenotype other than prostate cancer (p ≤ 10-7) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24 534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Outcome measurements and statistical analysis Odds ratios (ORs) and 95% confidence intervals (CIs) for aggressive prostate cancer were estimated. Results and limitations A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p = 1.6 × 10-6), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95% CI 1.16-1.27; p = 3.22 × 10-18). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95% CI 0.86-0.94; p = 2.5 × 10-6). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12, 95% CI 1.06-1.19; p = 4.67 × 10;bsupesup it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL. Conclusions We did not identify new SNPs for aggressive prostate cancer. However, rs16844874 may provide preliminary genetic evidence on the role of the glycine pathway in prostate cancer etiology. Patient summary We evaluated whether genetic variants associated with several traits are linked to the risk of aggressive prostate cancer. No new such variants were identified.
ISSN: 0302-2838
Rights: © European Association of Urology
Type: Article
Affiliation : National Institutes of Health 
University of Oxford 
German Cancer Research Center 
Harvard School of Public Health 
University of Southern California 
Imperial College London 
Cyprus University of Technology 
Fred Hutchinson Cancer Research Center 
National Institute for Health and Welfare 
American Cancer Society 
German Institute of Human Nutrition Potsdam-Rehbrücke 
National Institute for Public Health and the Environment 
University Medical Center 
University of Malaya 
Navarre Public Health Institute 
Consortium for Biomedical Research in Epidemiology and Public Health 
University of Cambridge 
Fondazione IRCCS Istituto Nazionale dei Tumori 
Aarhus University 
Hellenic Health Foundation 
Academy of Athens 
University of Hawaii 
Brigham and Women's Hospital 
Core Genotyping Facility Frederick National Laboratory for Cancer Research 
University of Ioannina 
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