Orestis A Panagiotou1, Ruth C Travis2, Daniele Campa3, Sonja I Berndt1, Sara Lindstrom4, Peter Kraft4, Fredrick R Schumacher5, Afshan Siddiq6, Stefania I Papatheodorou7, Janet L Stanford8, Demetrius Albanes1, Jarmo Virtamo9, Stephanie J Weinstein1, W Ryan Diver10, Susan M Gapstur10, Victoria L Stevens10, Heiner Boeing11, H Bas Bueno-de-Mesquita12, Aurelio Barricarte Gurrea13, Rudolf Kaaks14, Kay-Tee Khaw15, Vittorio Krogh16, Kim Overvad17, Elio Riboli18, Dimitrios Trichopoulos19, Edward Giovannucci20, Meir Stampfer4, Christopher Haiman5, Brian Henderson5, Loic Le Marchand21, J Michael Gaziano22, David J Hunter23, Stella Koutros1, Meredith Yeager24, Robert N Hoover1, Stephen J Chanock25, Sholom Wacholder1, Timothy J Key2, Konstantinos K Tsilidis26. 1. Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. 2. Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. 3. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 4. Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, MA, USA. 5. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 6. Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK. 7. Cyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Limassol, Cyprus. 8. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 9. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland. 10. Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA. 11. Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. 12. Department of Epidemiology and Biostatistics, Imperial College School of Public Health, London, UK; Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands; Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. 13. Navarre Public Health Institute, Pamplona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health, Madrid, Spain. 14. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. 15. Clinical Gerontology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. 16. Epidemiology and Prevention Unit, Department of Preventive & Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 17. Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. 18. Department of Epidemiology and Biostatistics, Imperial College School of Public Health, London, UK. 19. Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, MA, USA; Hellenic Health Foundation, Athens, Greece; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA. 20. Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, MA, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA. 21. University of Hawaii Cancer Center, Honolulu, HI, USA. 22. Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Aging, Brigham and Women's Hospital, Boston, MA, USA. 23. Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, MA, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA. 24. Core Genotyping Facility Frederick National Laboratory for Cancer Research, Gaithersburg, MD, USA. 25. Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Core Genotyping Facility Frederick National Laboratory for Cancer Research, Gaithersburg, MD, USA. 26. Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Department of Hygiene and Epidemiology, University of Ioannina, School of Medicine, Ioannina, Greece. Electronic address: kostas.tsilidis@ceu.ox.ac.uk.
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(-5)); 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.
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(-5)); 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.
Authors: So-Youn Shin; Ann-Kristin Petersen; Nicole Soranzo; Christian Gieger; Karsten Suhre; Robert P Mohney; David Meredith; Brigitte Wägele; Elisabeth Altmaier; Panos Deloukas; Jeanette Erdmann; Elin Grundberg; Christopher J Hammond; Martin Hrabé de Angelis; Gabi Kastenmüller; Anna Köttgen; Florian Kronenberg; Massimo Mangino; Christa Meisinger; Thomas Meitinger; Hans-Werner Mewes; Michael V Milburn; Cornelia Prehn; Johannes Raffler; Janina S Ried; Werner Römisch-Margl; Nilesh J Samani; Kerrin S Small; H-Erich Wichmann; Guangju Zhai; Thomas Illig; Tim D Spector; Jerzy Adamski Journal: Nature Date: 2011-08-31 Impact factor: 49.962
Authors: Zsofia Kote-Jarai; Ali Amin Al Olama; Graham G Giles; Gianluca Severi; Johanna Schleutker; Maren Weischer; Daniele Campa; Elio Riboli; Tim Key; Henrik Gronberg; David J Hunter; Peter Kraft; Michael J Thun; Sue Ingles; Stephen Chanock; Demetrius Albanes; Richard B Hayes; David E Neal; Freddie C Hamdy; Jenny L Donovan; Paul Pharoah; Fredrick Schumacher; Brian E Henderson; Janet L Stanford; Elaine A Ostrander; Karina Dalsgaard Sorensen; Thilo Dörk; Gerald Andriole; Joanne L Dickinson; Cezary Cybulski; Jan Lubinski; Amanda Spurdle; Judith A Clements; Suzanne Chambers; Joanne Aitken; R A Frank Gardiner; Stephen N Thibodeau; Dan Schaid; Esther M John; Christiane Maier; Walther Vogel; Kathleen A Cooney; Jong Y Park; Lisa Cannon-Albright; Hermann Brenner; Tomonori Habuchi; Hong-Wei Zhang; Yong-Jie Lu; Radka Kaneva; Ken Muir; Sara Benlloch; Daniel A Leongamornlert; Edward J Saunders; Malgorzata Tymrakiewicz; Nadiya Mahmud; Michelle Guy; Lynne T O'Brien; Rosemary A Wilkinson; Amanda L Hall; Emma J Sawyer; Tokhir Dadaev; Jonathan Morrison; David P Dearnaley; Alan Horwich; Robert A Huddart; Vincent S Khoo; Christopher C Parker; Nicholas Van As; Christopher J Woodhouse; Alan Thompson; Tim Christmas; Chris Ogden; Colin S Cooper; Aritaya Lophatonanon; Melissa C Southey; John L Hopper; Dallas R English; Tiina Wahlfors; Teuvo L J Tammela; Peter Klarskov; Børge G Nordestgaard; M Andreas Røder; Anne Tybjærg-Hansen; Stig E Bojesen; Ruth Travis; Federico Canzian; Rudolf Kaaks; Fredrik Wiklund; Markus Aly; Sara Lindstrom; W Ryan Diver; Susan Gapstur; Mariana C Stern; Roman Corral; Jarmo Virtamo; Angela Cox; Christopher A Haiman; Loic Le Marchand; Liesel Fitzgerald; Suzanne Kolb; Erika M Kwon; Danielle M Karyadi; Torben Falck Orntoft; Michael Borre; Andreas Meyer; Jürgen Serth; Meredith Yeager; Sonja I Berndt; James R Marthick; Briony Patterson; Dominika Wokolorczyk; Jyotsna Batra; Felicity Lose; Shannon K McDonnell; Amit D Joshi; Ahva Shahabi; Antje E Rinckleb; Ana Ray; Thomas A Sellers; Hui-Yi Lin; Robert A Stephenson; James Farnham; Heiko Muller; Dietrich Rothenbacher; Norihiko Tsuchiya; Shintaro Narita; Guang-Wen Cao; Chavdar Slavov; Vanio Mitev; Douglas F Easton; Rosalind A Eeles Journal: Nat Genet Date: 2011-07-10 Impact factor: 38.330
Authors: N Pashayan; S W Duffy; S Chowdhury; T Dent; H Burton; D E Neal; D F Easton; R Eeles; P Pharoah Journal: Br J Cancer Date: 2011-04-05 Impact factor: 7.640
Authors: Orestis A Panagiotou; Cristen J Willer; Joel N Hirschhorn; John P A Ioannidis Journal: Annu Rev Genomics Hum Genet Date: 2013-05-24 Impact factor: 8.929
Authors: Jonine D Figueroa; Yuanqing Ye; Afshan Siddiq; Montserrat Garcia-Closas; Nilanjan Chatterjee; Ludmila Prokunina-Olsson; Victoria K Cortessis; Charles Kooperberg; Olivier Cussenot; Simone Benhamou; Jennifer Prescott; Stefano Porru; Colin P Dinney; Núria Malats; Dalsu Baris; Mark Purdue; Eric J Jacobs; Demetrius Albanes; Zhaoming Wang; Xiang Deng; Charles C Chung; Wei Tang; H Bas Bueno-de-Mesquita; Dimitrios Trichopoulos; Börje Ljungberg; Françoise Clavel-Chapelon; Elisabete Weiderpass; Vittorio Krogh; Miren Dorronsoro; Ruth Travis; Anne Tjønneland; Paul Brenan; Jenny Chang-Claude; Elio Riboli; David Conti; Manuela Gago-Dominguez; Mariana C Stern; Malcolm C Pike; David Van Den Berg; Jian-Min Yuan; Chancellor Hohensee; Rebecca Rodabough; Geraldine Cancel-Tassin; Morgan Roupret; Eva Comperat; Constance Chen; Immaculata De Vivo; Edward Giovannucci; David J Hunter; Peter Kraft; Sara Lindstrom; Angela Carta; Sofia Pavanello; Cecilia Arici; Giuseppe Mastrangelo; Ashish M Kamat; Seth P Lerner; H Barton Grossman; Jie Lin; Jian Gu; Xia Pu; Amy Hutchinson; Laurie Burdette; William Wheeler; Manolis Kogevinas; Adonina Tardón; Consol Serra; Alfredo Carrato; Reina García-Closas; Josep Lloreta; Molly Schwenn; Margaret R Karagas; Alison Johnson; Alan Schned; Karla R Armenti; G M Hosain; Gerald Andriole; Robert Grubb; Amanda Black; W Ryan Diver; Susan M Gapstur; Stephanie J Weinstein; Jarmo Virtamo; Chris A Haiman; Maria T Landi; Neil Caporaso; Joseph F Fraumeni; Paolo Vineis; Xifeng Wu; Debra T Silverman; Stephen Chanock; Nathaniel Rothman Journal: Hum Mol Genet Date: 2013-10-24 Impact factor: 6.150
Authors: Dana B Hancock; María Soler Artigas; Sina A Gharib; Amanda Henry; Ani Manichaikul; Adaikalavan Ramasamy; Daan W Loth; Medea Imboden; Beate Koch; Wendy L McArdle; Albert V Smith; Joanna Smolonska; Akshay Sood; Wenbo Tang; Jemma B Wilk; Guangju Zhai; Jing Hua Zhao; Hugues Aschard; Kristin M Burkart; Ivan Curjuric; Mark Eijgelsheim; Paul Elliott; Xiangjun Gu; Tamara B Harris; Christer Janson; Georg Homuth; Pirro G Hysi; Jason Z Liu; Laura R Loehr; Kurt Lohman; Ruth J F Loos; Alisa K Manning; Kristin D Marciante; Ma'en Obeidat; Dirkje S Postma; Melinda C Aldrich; Guy G Brusselle; Ting-hsu Chen; Gudny Eiriksdottir; Nora Franceschini; Joachim Heinrich; Jerome I Rotter; Cisca Wijmenga; O Dale Williams; Amy R Bentley; Albert Hofman; Cathy C Laurie; Thomas Lumley; Alanna C Morrison; Bonnie R Joubert; Fernando Rivadeneira; David J Couper; Stephen B Kritchevsky; Yongmei Liu; Matthias Wjst; Louise V Wain; Judith M Vonk; André G Uitterlinden; Thierry Rochat; Stephen S Rich; Bruce M Psaty; George T O'Connor; Kari E North; Daniel B Mirel; Bernd Meibohm; Lenore J Launer; Kay-Tee Khaw; Anna-Liisa Hartikainen; Christopher J Hammond; Sven Gläser; Jonathan Marchini; Peter Kraft; Nicholas J Wareham; Henry Völzke; Bruno H C Stricker; Timothy D Spector; Nicole M Probst-Hensch; Deborah Jarvis; Marjo-Riitta Jarvelin; Susan R Heckbert; Vilmundur Gudnason; H Marike Boezen; R Graham Barr; Patricia A Cassano; David P Strachan; Myriam Fornage; Ian P Hall; Josée Dupuis; Martin D Tobin; Stephanie J London Journal: PLoS Genet Date: 2012-12-20 Impact factor: 5.917
Authors: Carissa C Jones; Yuki Bradford; Christopher I Amos; William J Blot; Stephen J Chanock; Curtis C Harris; Ann G Schwartz; Margaret R Spitz; John K Wiencke; Margaret R Wrensch; Xifeng Wu; Melinda C Aldrich Journal: Cancer Epidemiol Biomarkers Prev Date: 2019-03-20 Impact factor: 4.254
Authors: Yi-Hsuan Wu; Rebecca E Graff; Michael N Passarelli; Joshua D Hoffman; Elad Ziv; Thomas J Hoffmann; John S Witte Journal: Cancer Epidemiol Biomarkers Prev Date: 2017-11-17 Impact factor: 4.254
Authors: Eunjung Lee; Daniel O Stram; Weronica E Ek; Lynn E Onstad; Stuart MacGregor; Puya Gharahkhani; Weimin Ye; Jesper Lagergren; Nicholas J Shaheen; Liam J Murray; Laura J Hardie; Marilie D Gammon; Wong-Ho Chow; Harvey A Risch; Douglas A Corley; David M Levine; David C Whiteman; Leslie Bernstein; Nigel C Bird; Thomas L Vaughan; Anna H Wu Journal: Cancer Epidemiol Biomarkers Prev Date: 2015-09-12 Impact factor: 4.254
Authors: Inga Peter; Marla Dubinsky; Susan Bressman; Andrew Park; Changyue Lu; Naijun Chen; Anthony Wang Journal: JAMA Neurol Date: 2018-08-01 Impact factor: 18.302
Authors: Antonio Di Narzo; Itziar Frades; Heidi M Crane; Paul K Crane; Jean-Sebastian Hulot; Andrew Kasarskis; Amy Hart; Carmen Argmann; Marla Dubinsky; Inga Peter; Ke Hao Journal: Hum Genet Date: 2021-01-16 Impact factor: 5.881
Authors: Vasiliki I Dimitrakopoulou; Konstantinos K Tsilidis; Philip C Haycock; Niki L Dimou; Kawthar Al-Dabhani; Richard M Martin; Sarah J Lewis; Marc J Gunter; Alison Mondul; Irene M Shui; Evropi Theodoratou; Katharina Nimptsch; Sara Lindström; Demetrius Albanes; Tilman Kühn; Timothy J Key; Ruth C Travis; Karani Santhanakrishnan Vimaleswaran; Peter Kraft; Brandon L Pierce; Joellen M Schildkraut Journal: BMJ Date: 2017-10-31