Weiqiang Li1, Mridu Middha1, Mesude Bicak1, Daniel D Sjoberg2, Emily Vertosick2, Anders Dahlin3, Christel Häggström4, Göran Hallmans5, Ann-Charlotte Rönn6, Pär Stattin7, Olle Melander3, David Ulmert8, Hans Lilja9, Robert J Klein10. 1. Icahn Institute for Genomics and Multiscale Biology and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 3. Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden. 4. Department of Biobank Research, Umeå University, Umeå, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. 5. Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden. 6. Clinical Research Center, Karolinska University Hospital, Huddinge, Sweden. 7. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. 8. Molecular Pharmacology Program, Sloan Kettering Institute, New York, NY, USA. 9. Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Department of Translational Medicine, Lund University, Malmö, Sweden. 10. Icahn Institute for Genomics and Multiscale Biology and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: robert.klein@mssm.edu.
Abstract
BACKGROUND: Most men diagnosed with prostate cancer have low-risk cancers. How to predict prostate cancer progression at the time of diagnosis remains challenging. OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) associated with death from prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Blood samples from 11 506 men in Sweden were collected during 1991-1996. Of these, 1053 men were diagnosed with prostate cancer and 245 died from the disease. Stage and grade at diagnosis and outcome information were obtained, and DNA from all cases was genotyped. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A total of 6 126 633 SNPs were tested for association with prostate-cancer-specific survival time using a Cox proportional hazard model, adjusted for age, stage, and grade at diagnosis. A value of 1×10-6 was used as suggestive significance threshold. Positive candidate SNPs were tested for association with gene expression using expression quantitative trait locus analysis. RESULTS AND LIMITATIONS: We found 12 SNPs at seven independent loci associated with prostate-cancer-specific survival time. One of 6 126 633 SNPs tested reached genome-wide significance (p<5×10-8) and replicated in an independent cohort: rs73055188 (p=5.27×10-9, per-allele hazard ratio [HR]=2.27, 95% confidence interval [CI] 1.72-2.98) in the AOX1 gene. A second SNP reached a suggestive level of significance (p<1×10-6) and replicated in an independent cohort: rs2702185 (p=7.1×10-7, per-allele HR=2.55, 95% CI=1.76-3.69) in the SMG7 gene. The SNP rs73055188 is correlated with AOX1 expression levels, which is associated with biochemical recurrence of prostate cancer in independent cohorts. This association is yet to be validated in other ethnic groups. CONCLUSIONS: The SNP rs73055188 at the AOX1 locus is associated with prostate-cancer-specific survival time, and AOX1 gene expression level is correlated with biochemical recurrence of prostate cancer. PATIENT SUMMARY: We identify two genetic markers that are associated with prostate-cancer-specific survival time.
BACKGROUND: Most men diagnosed with prostate cancer have low-risk cancers. How to predict prostate cancer progression at the time of diagnosis remains challenging. OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) associated with death from prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Blood samples from 11 506 men in Sweden were collected during 1991-1996. Of these, 1053 men were diagnosed with prostate cancer and 245 died from the disease. Stage and grade at diagnosis and outcome information were obtained, and DNA from all cases was genotyped. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A total of 6 126 633 SNPs were tested for association with prostate-cancer-specific survival time using a Cox proportional hazard model, adjusted for age, stage, and grade at diagnosis. A value of 1×10-6 was used as suggestive significance threshold. Positive candidate SNPs were tested for association with gene expression using expression quantitative trait locus analysis. RESULTS AND LIMITATIONS: We found 12 SNPs at seven independent loci associated with prostate-cancer-specific survival time. One of 6 126 633 SNPs tested reached genome-wide significance (p<5×10-8) and replicated in an independent cohort: rs73055188 (p=5.27×10-9, per-allele hazard ratio [HR]=2.27, 95% confidence interval [CI] 1.72-2.98) in the AOX1 gene. A second SNP reached a suggestive level of significance (p<1×10-6) and replicated in an independent cohort: rs2702185 (p=7.1×10-7, per-allele HR=2.55, 95% CI=1.76-3.69) in the SMG7 gene. The SNP rs73055188 is correlated with AOX1 expression levels, which is associated with biochemical recurrence of prostate cancer in independent cohorts. This association is yet to be validated in other ethnic groups. CONCLUSIONS: The SNP rs73055188 at the AOX1 locus is associated with prostate-cancer-specific survival time, and AOX1 gene expression level is correlated with biochemical recurrence of prostate cancer. PATIENT SUMMARY: We identify two genetic markers that are associated with prostate-cancer-specific survival time.
Authors: Laurent Briollais; Hilmi Ozcelik; Jingxiong Xu; Maciej Kwiatkowski; Emilie Lalonde; Dorota H Sendorek; Neil E Fleshner; Franz Recker; Cynthia Kuk; Ekaterina Olkhov-Mitsel; Sevtap Savas; Sally Hanna; Tristan Juvet; Geoffrey A Hunter; Matt Friedlander; Hong Li; Karen Chadwick; Ioannis Prassas; Antoninus Soosaipillai; Marco Randazzo; John Trachtenberg; Ants Toi; Yu-Jia Shiah; Michael Fraser; Theodorus van der Kwast; Robert G Bristow; Bharati Bapat; Eleftherios P Diamandis; Paul C Boutros; Alexandre R Zlotta Journal: J Natl Cancer Inst Date: 2017-04-01 Impact factor: 13.506
Authors: Mieke Van Hemelrijck; Annette Wigertz; Fredrik Sandin; Hans Garmo; Karin Hellström; Per Fransson; Anders Widmark; Mats Lambe; Jan Adolfsson; Eberhard Varenhorst; Jan-Erik Johansson; Pär Stattin Journal: Int J Epidemiol Date: 2012-05-04 Impact factor: 7.196
Authors: Ali Amin Al Olama; Zsofia Kote-Jarai; Fredrick R Schumacher; Fredrik Wiklund; Sonja I Berndt; Sara Benlloch; Graham G Giles; Gianluca Severi; David E Neal; Freddie C Hamdy; Jenny L Donovan; David J Hunter; Brian E Henderson; Michael J Thun; Michael Gaziano; Edward L Giovannucci; Afshan Siddiq; Ruth C Travis; David G Cox; Federico Canzian; Elio Riboli; Timothy J Key; Gerald Andriole; Demetrius Albanes; Richard B Hayes; Johanna Schleutker; Anssi Auvinen; Teuvo L J Tammela; Maren Weischer; Janet L Stanford; Elaine A Ostrander; Cezary Cybulski; Jan Lubinski; Stephen N Thibodeau; Daniel J Schaid; Karina D Sorensen; Jyotsna Batra; Judith A Clements; Suzanne Chambers; Joanne Aitken; Robert A Gardiner; Christiane Maier; Walther Vogel; Thilo Dörk; Hermann Brenner; Tomonori Habuchi; Sue Ingles; Esther M John; Joanne L Dickinson; Lisa Cannon-Albright; Manuel R Teixeira; Radka Kaneva; Hong-Wei Zhang; Yong-Jie Lu; Jong Y Park; Kathleen A Cooney; Kenneth R Muir; Daniel A Leongamornlert; Edward Saunders; Malgorzata Tymrakiewicz; Nadiya Mahmud; Michelle Guy; Koveela Govindasami; 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 Dudderidge; Chris Ogden; Colin S Cooper; Artitaya Lophatonanon; Melissa C Southey; John L Hopper; Dallas English; Jarmo Virtamo; Loic Le Marchand; Daniele Campa; Rudolf Kaaks; Sara Lindstrom; W Ryan Diver; Susan Gapstur; Meredith Yeager; Angela Cox; Mariana C Stern; Roman Corral; Markus Aly; William Isaacs; Jan Adolfsson; Jianfeng Xu; S Lilly Zheng; Tiina Wahlfors; Kimmo Taari; Paula Kujala; Peter Klarskov; Børge G Nordestgaard; M Andreas Røder; Ruth Frikke-Schmidt; Stig E Bojesen; Liesel M FitzGerald; Suzanne Kolb; Erika M Kwon; Danielle M Karyadi; Torben Falck Orntoft; Michael Borre; Antje Rinckleb; Manuel Luedeke; Kathleen Herkommer; Andreas Meyer; Jürgen Serth; James R Marthick; Briony Patterson; Dominika Wokolorczyk; Amanda Spurdle; Felicity Lose; Shannon K McDonnell; Amit D Joshi; Ahva Shahabi; Pedro Pinto; Joana Santos; Ana Ray; Thomas A Sellers; Hui-Yi Lin; Robert A Stephenson; Craig Teerlink; Heiko Muller; Dietrich Rothenbacher; Norihiko Tsuchiya; Shintaro Narita; Guang-Wen Cao; Chavdar Slavov; Vanio Mitev; Stephen Chanock; Henrik Gronberg; Christopher A Haiman; Peter Kraft; Douglas F Easton; Rosalind A Eeles Journal: Hum Mol Genet Date: 2012-10-12 Impact factor: 6.150
Authors: Xiaoyu Song; Meng Ru; Zoe Steinsnyder; Kaitlyn Tkachuk; Ryan P Kopp; John Sullivan; Zeynep H Gümüş; Kenneth Offit; Vijai Joseph; Robert J Klein Journal: Cancer Epidemiol Biomarkers Prev Date: 2022-07-01 Impact factor: 4.090
Authors: Weiqiang Li; Mesude Bicak; Daniel D Sjoberg; Emily Vertosick; Anders Dahlin; Olle Melander; David Ulmert; Hans Lilja; Robert J Klein Journal: Prostate Date: 2020-09-11 Impact factor: 4.104