August Blackburn1, Desiree Wilson1, Jonathan Gelfond2,3, Li Yao4, Javier Hernandez5,3, Ian M Thompson5,3, Robin J Leach1,5,3, Donna M Lehman4,3. 1. University of Texas Health Science Center at San Antonio, Department of Cellular and Structural Biology. 2. University of Texas Health Science Center at San Antonio, Department of Epidemiology and Biostatistics. 3. University of Texas Health Science Center at San Antonio, Cancer Therapy and Research Center. 4. University of Texas Health Science Center at San Antonio, Department of Medicine - Division of Clinical Epidemiology. 5. University of Texas Health Science Center at San Antonio, Department of Urology.
Abstract
OBJECTIVE: Two recent studies have reported novel heritable copy number variants on chromosomes 2p, 15q, and 12q to be associated with prostate cancer (PCa) risk in non-Hispanic Caucasians. The goal of this study was to determine whether these findings could be independently confirmed in the Caucasian population from the South Texas area. METHODS AND MATERIALS: The study subjects consisted of participants of the San Antonio Biomarkers of Risk for PCa cohort and additional cases ascertained in the same metropolitan area. We genotyped all 7 of the reported copy number variants using real-time quantitative polymerase chain reaction in 1,536 (317 cases and 1,219 controls) non-Hispanic Caucasian men, and additionally, we genotyped 632 (191 cases and 441 controls) Hispanic Caucasian men for one of these variants, a deletion on 2p24.3. RESULTS: Association of the deletion on 2p24.3 with overall PCa risk did not meet our significance criteria but was consistent with previous reports (odds ratio, 1.40; 95% confidence interval 0.99-2.00; P = 0.06). Among Hispanic Caucasians, this deletion is much less prevalent (minor allele frequencies of 0.059 and 0.024 in non-Hispanic and Hispanic Caucasians, respectively) and did not show evidence of association with risk for PCa. Interestingly, among non-Hispanic Caucasians, carrying a homozygous deletion of 2p24.3 was significantly associated with high-grade PCa as defined by Gleason score sum ≥8 (odds ratio, 27.99; 95% confidence interval 1.99-392.6; P = 0.007 [the Fisher exact test]). The remaining 6 copy number variable regions either were not polymorphic in our cohort of non-Hispanic Caucasians or showed no evidence of association. CONCLUSIONS: Our findings are consistent with the reported observation that a heritable deletion on 2p24.3 is associated with PCa risk in non-Hispanic Caucasians. Additionally, our observations indicate that the 2p24.3 variant is associated with risk for high-grade PCa in a recessive manner. We were unable to replicate any association with PCa for the variants on chromosomes 15q and 12q, which may be explained by regional population differences in low frequency variants and disease heterogeneity. Published by Elsevier Inc.
OBJECTIVE: Two recent studies have reported novel heritable copy number variants on chromosomes 2p, 15q, and 12q to be associated with prostate cancer (PCa) risk in non-Hispanic Caucasians. The goal of this study was to determine whether these findings could be independently confirmed in the Caucasian population from the South Texas area. METHODS AND MATERIALS: The study subjects consisted of participants of the San Antonio Biomarkers of Risk for PCa cohort and additional cases ascertained in the same metropolitan area. We genotyped all 7 of the reported copy number variants using real-time quantitative polymerase chain reaction in 1,536 (317 cases and 1,219 controls) non-Hispanic Caucasian men, and additionally, we genotyped 632 (191 cases and 441 controls) Hispanic Caucasian men for one of these variants, a deletion on 2p24.3. RESULTS: Association of the deletion on 2p24.3 with overall PCa risk did not meet our significance criteria but was consistent with previous reports (odds ratio, 1.40; 95% confidence interval 0.99-2.00; P = 0.06). Among Hispanic Caucasians, this deletion is much less prevalent (minor allele frequencies of 0.059 and 0.024 in non-Hispanic and Hispanic Caucasians, respectively) and did not show evidence of association with risk for PCa. Interestingly, among non-Hispanic Caucasians, carrying a homozygous deletion of 2p24.3 was significantly associated with high-grade PCa as defined by Gleason score sum ≥8 (odds ratio, 27.99; 95% confidence interval 1.99-392.6; P = 0.007 [the Fisher exact test]). The remaining 6 copy number variable regions either were not polymorphic in our cohort of non-Hispanic Caucasians or showed no evidence of association. CONCLUSIONS: Our findings are consistent with the reported observation that a heritable deletion on 2p24.3 is associated with PCa risk in non-Hispanic Caucasians. Additionally, our observations indicate that the 2p24.3 variant is associated with risk for high-grade PCa in a recessive manner. We were unable to replicate any association with PCa for the variants on chromosomes 15q and 12q, which may be explained by regional population differences in low frequency variants and disease heterogeneity. Published by Elsevier Inc.
Authors: Mark I McCarthy; Gonçalo R Abecasis; Lon R Cardon; David B Goldstein; Julian Little; John P A Ioannidis; Joel N Hirschhorn Journal: Nat Rev Genet Date: 2008-05 Impact factor: 53.242
Authors: David M Altshuler; Richard A Gibbs; Leena Peltonen; David M Altshuler; Richard A Gibbs; Leena Peltonen; Emmanouil Dermitzakis; Stephen F Schaffner; Fuli Yu; Leena Peltonen; Emmanouil Dermitzakis; Penelope E Bonnen; David M Altshuler; Richard A Gibbs; Paul I W de Bakker; Panos Deloukas; Stacey B Gabriel; Rhian Gwilliam; Sarah Hunt; Michael Inouye; Xiaoming Jia; Aarno Palotie; Melissa Parkin; Pamela Whittaker; Fuli Yu; Kyle Chang; Alicia Hawes; Lora R Lewis; Yanru Ren; David Wheeler; Richard A Gibbs; Donna Marie Muzny; Chris Barnes; Katayoon Darvishi; Matthew Hurles; Joshua M Korn; Kati Kristiansson; Charles Lee; Steven A McCarrol; James Nemesh; Emmanouil Dermitzakis; Alon Keinan; Stephen B Montgomery; Samuela Pollack; Alkes L Price; Nicole Soranzo; Penelope E Bonnen; Richard A Gibbs; Claudia Gonzaga-Jauregui; Alon Keinan; Alkes L Price; Fuli Yu; Verneri Anttila; Wendy Brodeur; Mark J Daly; Stephen Leslie; Gil McVean; Loukas Moutsianas; Huy Nguyen; Stephen F Schaffner; Qingrun Zhang; Mohammed J R Ghori; Ralph McGinnis; William McLaren; Samuela Pollack; Alkes L Price; Stephen F Schaffner; Fumihiko Takeuchi; Sharon R Grossman; Ilya Shlyakhter; Elizabeth B Hostetter; Pardis C Sabeti; Clement A Adebamowo; Morris W Foster; Deborah R Gordon; Julio Licinio; Maria Cristina Manca; Patricia A Marshall; Ichiro Matsuda; Duncan Ngare; Vivian Ota Wang; Deepa Reddy; Charles N Rotimi; Charmaine D Royal; Richard R Sharp; Changqing Zeng; Lisa D Brooks; Jean E McEwen Journal: Nature Date: 2010-09-02 Impact factor: 49.962
Authors: P Lichtenstein; N V Holm; P K Verkasalo; A Iliadou; J Kaprio; M Koskenvuo; E Pukkala; A Skytthe; K Hemminki Journal: N Engl J Med Date: 2000-07-13 Impact factor: 91.245
Authors: Francesca Demichelis; Sunita R Setlur; Samprit Banerjee; Dimple Chakravarty; Jin Yun Helen Chen; Chen X Chen; Julie Huang; Himisha Beltran; Derek A Oldridge; Naoki Kitabayashi; Birgit Stenzel; Georg Schaefer; Wolfgang Horninger; Jasmin Bektic; Arul M Chinnaiyan; Sagit Goldenberg; Javed Siddiqui; Meredith M Regan; Michale Kearney; T David Soong; David S Rickman; Olivier Elemento; John T Wei; Douglas S Scherr; Martin A Sanda; Georg Bartsch; Charles Lee; Helmut Klocker; Mark A Rubin Journal: Proc Natl Acad Sci U S A Date: 2012-04-10 Impact factor: 11.205
Authors: Gonçalo R Abecasis; David Altshuler; Adam Auton; Lisa D Brooks; Richard M Durbin; Richard A Gibbs; Matt E Hurles; Gil A McVean Journal: Nature Date: 2010-10-28 Impact factor: 49.962
Authors: Nick Craddock; Matthew E Hurles; Niall Cardin; Richard D Pearson; Vincent Plagnol; Samuel Robson; Damjan Vukcevic; Chris Barnes; Donald F Conrad; Eleni Giannoulatou; Chris Holmes; Jonathan L Marchini; Kathy Stirrups; Martin D Tobin; Louise V Wain; Chris Yau; Jan Aerts; Tariq Ahmad; T Daniel Andrews; Hazel Arbury; Anthony Attwood; Adam Auton; Stephen G Ball; Anthony J Balmforth; Jeffrey C Barrett; Inês Barroso; Anne Barton; Amanda J Bennett; Sanjeev Bhaskar; Katarzyna Blaszczyk; John Bowes; Oliver J Brand; Peter S Braund; Francesca Bredin; Gerome Breen; Morris J Brown; Ian N Bruce; Jaswinder Bull; Oliver S Burren; John Burton; Jake Byrnes; Sian Caesar; Chris M Clee; Alison J Coffey; John M C Connell; Jason D Cooper; Anna F Dominiczak; Kate Downes; Hazel E Drummond; Darshna Dudakia; Andrew Dunham; Bernadette Ebbs; Diana Eccles; Sarah Edkins; Cathryn Edwards; Anna Elliot; Paul Emery; David M Evans; Gareth Evans; Steve Eyre; Anne Farmer; I Nicol Ferrier; Lars Feuk; Tomas Fitzgerald; Edward Flynn; Alistair Forbes; Liz Forty; Jayne A Franklyn; Rachel M Freathy; Polly Gibbs; Paul Gilbert; Omer Gokumen; Katherine Gordon-Smith; Emma Gray; Elaine Green; Chris J Groves; Detelina Grozeva; Rhian Gwilliam; Anita Hall; Naomi Hammond; Matt Hardy; Pile Harrison; Neelam Hassanali; Husam Hebaishi; Sarah Hines; Anne Hinks; Graham A Hitman; Lynne Hocking; Eleanor Howard; Philip Howard; Joanna M M Howson; Debbie Hughes; Sarah Hunt; John D Isaacs; Mahim Jain; Derek P Jewell; Toby Johnson; Jennifer D Jolley; Ian R Jones; Lisa A Jones; George Kirov; Cordelia F Langford; Hana Lango-Allen; G Mark Lathrop; James Lee; Kate L Lee; Charlie Lees; Kevin Lewis; Cecilia M Lindgren; Meeta Maisuria-Armer; Julian Maller; John Mansfield; Paul Martin; Dunecan C O Massey; Wendy L McArdle; Peter McGuffin; Kirsten E McLay; Alex Mentzer; Michael L Mimmack; Ann E Morgan; Andrew P Morris; Craig Mowat; Simon Myers; William Newman; Elaine R Nimmo; Michael C O'Donovan; Abiodun Onipinla; Ifejinelo Onyiah; Nigel R Ovington; Michael J Owen; Kimmo Palin; Kirstie Parnell; David Pernet; John R B Perry; Anne Phillips; Dalila Pinto; Natalie J Prescott; Inga Prokopenko; Michael A Quail; Suzanne Rafelt; Nigel W Rayner; Richard Redon; David M Reid; Susan M Ring; Neil Robertson; Ellie Russell; David St Clair; Jennifer G Sambrook; Jeremy D Sanderson; Helen Schuilenburg; Carol E Scott; Richard Scott; Sheila Seal; Sue Shaw-Hawkins; Beverley M Shields; Matthew J Simmonds; Debbie J Smyth; Elilan Somaskantharajah; Katarina Spanova; Sophia Steer; Jonathan Stephens; Helen E Stevens; Millicent A Stone; Zhan Su; Deborah P M Symmons; John R Thompson; Wendy Thomson; Mary E Travers; Clare Turnbull; Armand Valsesia; Mark Walker; Neil M Walker; Chris Wallace; Margaret Warren-Perry; Nicholas A Watkins; John Webster; Michael N Weedon; Anthony G Wilson; Matthew Woodburn; B Paul Wordsworth; Allan H Young; Eleftheria Zeggini; Nigel P Carter; Timothy M Frayling; Charles Lee; Gil McVean; Patricia B Munroe; Aarno Palotie; Stephen J Sawcer; Stephen W Scherer; David P Strachan; Chris Tyler-Smith; Matthew A Brown; Paul R Burton; Mark J Caulfield; Alastair Compston; Martin Farrall; Stephen C L Gough; Alistair S Hall; Andrew T Hattersley; Adrian V S Hill; Christopher G Mathew; Marcus Pembrey; Jack Satsangi; Michael R Stratton; Jane Worthington; Panos Deloukas; Audrey Duncanson; Dominic P Kwiatkowski; Mark I McCarthy; Willem Ouwehand; Miles Parkes; Nazneen Rahman; John A Todd; Nilesh J Samani; Peter Donnelly Journal: Nature Date: 2010-04-01 Impact factor: 49.962
Authors: Donald F Conrad; Dalila Pinto; Richard Redon; Lars Feuk; Omer Gokcumen; Yujun Zhang; Jan Aerts; T Daniel Andrews; Chris Barnes; Peter Campbell; Tomas Fitzgerald; Min Hu; Chun Hwa Ihm; Kati Kristiansson; Daniel G Macarthur; Jeffrey R Macdonald; Ifejinelo Onyiah; Andy Wing Chun Pang; Sam Robson; Kathy Stirrups; Armand Valsesia; Klaudia Walter; John Wei; Chris Tyler-Smith; Nigel P Carter; Charles Lee; Stephen W Scherer; Matthew E Hurles Journal: Nature Date: 2009-10-07 Impact factor: 49.962
Authors: Chris Barnes; Vincent Plagnol; Tomas Fitzgerald; Richard Redon; Jonathan Marchini; David Clayton; Matthew E Hurles Journal: Nat Genet Date: 2008-09-07 Impact factor: 38.330