BACKGROUND: Prostate cancer (PCa) is characterized by its tendency to be multifocal. However, few studies have investigated the endogenous factors that explain the multifocal disease. The primary objective of the current study is to test whether inherited PCa risk is associated with multifocal tumors in PCa patients. METHODS: Subjects in this study were PCa patients of European ancestry undergoing active surveillance at Johns Hopkins Hospital (N = 805) and NorthShore University HealthSystem (N = 432). The inherited risk was measured by genetic risk score (GRS), an odds ratio-weighted and population-standardized polygenic risk score based on known risk-associated single nucleotide polymorphisms. PCa multifocality was indirectly measured by the number and laterality of positive tumor cores from a 12-core systematic biopsy. RESULTS: In the combined cohort, 35.7% and 66.3% of patients had ≥2 tumor cores at the initial diagnostic biopsy and on at least one subsequent surveillance biopsy, respectively. For tumor laterality, 7.8% and 47.8% of patients had bilateral tumor cores at diagnostic and surveillance biopsies, respectively. We found, for the first time, that patients with higher numbers of positive cores at diagnostic and surveillance biopsies, respectively, had significantly higher mean GRS values; p = .01 and p = 5.94E-04. Additionally, patients with bilateral tumors at diagnostic and surveillance biopsies, respectively, had significantly higher mean GRS values than those with unilateral tumors; p = .04 and p = .01. In contrast, no association was found between GRS and maximum core length of tumor or tumor grade at diagnostic/surveillance biopsies (all p > .05). Finally, we observed a modest trend that patients with higher GRS quartiles had a higher risk for tumor upgrading on surveillance biopsies. The trend, however, was not statistically significant (p > .05). CONCLUSIONS: The associations of GRS with two measurements of PCa multifocality (core numbers and laterality) provide novel and consistent evidence for the link between inherited PCa risk and multifocal tumors.
BACKGROUND: Prostate cancer (PCa) is characterized by its tendency to be multifocal. However, few studies have investigated the endogenous factors that explain the multifocal disease. The primary objective of the current study is to test whether inherited PCa risk is associated with multifocal tumors in PCa patients. METHODS: Subjects in this study were PCa patients of European ancestry undergoing active surveillance at Johns Hopkins Hospital (N = 805) and NorthShore University HealthSystem (N = 432). The inherited risk was measured by genetic risk score (GRS), an odds ratio-weighted and population-standardized polygenic risk score based on known risk-associated single nucleotide polymorphisms. PCa multifocality was indirectly measured by the number and laterality of positive tumor cores from a 12-core systematic biopsy. RESULTS: In the combined cohort, 35.7% and 66.3% of patients had ≥2 tumor cores at the initial diagnostic biopsy and on at least one subsequent surveillance biopsy, respectively. For tumor laterality, 7.8% and 47.8% of patients had bilateral tumor cores at diagnostic and surveillance biopsies, respectively. We found, for the first time, that patients with higher numbers of positive cores at diagnostic and surveillance biopsies, respectively, had significantly higher mean GRS values; p = .01 and p = 5.94E-04. Additionally, patients with bilateral tumors at diagnostic and surveillance biopsies, respectively, had significantly higher mean GRS values than those with unilateral tumors; p = .04 and p = .01. In contrast, no association was found between GRS and maximum core length of tumor or tumor grade at diagnostic/surveillance biopsies (all p > .05). Finally, we observed a modest trend that patients with higher GRS quartiles had a higher risk for tumor upgrading on surveillance biopsies. The trend, however, was not statistically significant (p > .05). CONCLUSIONS: The associations of GRS with two measurements of PCa multifocality (core numbers and laterality) provide novel and consistent evidence for the link between inherited PCa risk and multifocal tumors.
Authors: Michael C Haffner; Wilbert Zwart; Martine P Roudier; Lawrence D True; William G Nelson; Jonathan I Epstein; Angelo M De Marzo; Peter S Nelson; Srinivasan Yegnasubramanian Journal: Nat Rev Urol Date: 2020-12-16 Impact factor: 14.432
Authors: Chee L Goh; Edward J Saunders; Daniel A Leongamornlert; Malgorzata Tymrakiewicz; Karen Thomas; Elizabeth D Selvadurai; Ruth Woode-Amissah; Tokhir Dadaev; Nadiya Mahmud; Elena Castro; David Olmos; Michelle Guy; Koveela Govindasami; Lynne T O'Brien; Amanda L Hall; Rosemary A Wilkinson; Emma J Sawyer; Ali Amin Al Olama; Douglas F Easton; Zsofia Kote-Jarai; Chris C Parker; Rosalind A Eeles Journal: BJU Int Date: 2013-01-15 Impact factor: 5.588
Authors: A Karim Kader; Jielin Sun; Sarah D Isaacs; Kathleen E Wiley; Guifang Yan; Seong-Tae Kim; Helen Fedor; Angelo M DeMarzo; Jonathan I Epstein; Patrick C Walsh; Alan W Partin; Bruce Trock; S Lilly Zheng; Jianfeng Xu; William Isaacs Journal: Prostate Date: 2009-08-01 Impact factor: 4.104
Authors: Haitao Chen; Rong Na; Vignesh T Packiam; Carly A Conran; Deke Jiang; Sha Tao; Hongjie Yu; Xiaoling Lin; Wei Meng; S Lilly Zheng; Charles B Brendler; Brian T Helfand; Jianfeng Xu Journal: Prostate Date: 2017-07-02 Impact factor: 4.104
Authors: Fredrick R Schumacher; Ali Amin Al Olama; Sonja I Berndt; Sara Benlloch; Mahbubl Ahmed; Edward J Saunders; Tokhir Dadaev; Daniel Leongamornlert; Ezequiel Anokian; Clara Cieza-Borrella; Chee Goh; Mark N Brook; Xin Sheng; Laura Fachal; Joe Dennis; Jonathan Tyrer; Kenneth Muir; Artitaya Lophatananon; Victoria L Stevens; Susan M Gapstur; Brian D Carter; Catherine M Tangen; Phyllis J Goodman; Ian M Thompson; Jyotsna Batra; Suzanne Chambers; Leire Moya; Judith Clements; Lisa Horvath; Wayne Tilley; Gail P Risbridger; Henrik Gronberg; Markus Aly; Tobias Nordström; Paul Pharoah; Nora Pashayan; Johanna Schleutker; Teuvo L J Tammela; Csilla Sipeky; Anssi Auvinen; Demetrius Albanes; Stephanie Weinstein; Alicja Wolk; Niclas Håkansson; Catharine M L West; Alison M Dunning; Neil Burnet; Lorelei A Mucci; Edward Giovannucci; Gerald L Andriole; Olivier Cussenot; Géraldine Cancel-Tassin; Stella Koutros; Laura E Beane Freeman; Karina Dalsgaard Sorensen; Torben Falck Orntoft; Michael Borre; Lovise Maehle; Eli Marie Grindedal; David E Neal; Jenny L Donovan; Freddie C Hamdy; Richard M Martin; Ruth C Travis; Tim J Key; Robert J Hamilton; Neil E Fleshner; Antonio Finelli; Sue Ann Ingles; Mariana C Stern; Barry S Rosenstein; Sarah L Kerns; Harry Ostrer; Yong-Jie Lu; Hong-Wei Zhang; Ninghan Feng; Xueying Mao; Xin Guo; Guomin Wang; Zan Sun; Graham G Giles; Melissa C Southey; Robert J MacInnis; Liesel M FitzGerald; Adam S Kibel; Bettina F Drake; Ana Vega; Antonio Gómez-Caamaño; Robert Szulkin; Martin Eklund; Manolis Kogevinas; Javier Llorca; Gemma Castaño-Vinyals; Kathryn L Penney; Meir Stampfer; Jong Y Park; Thomas A Sellers; Hui-Yi Lin; Janet L Stanford; Cezary Cybulski; Dominika Wokolorczyk; Jan Lubinski; Elaine A Ostrander; Milan S Geybels; Børge G Nordestgaard; Sune F Nielsen; Maren Weischer; Rasmus Bisbjerg; Martin Andreas Røder; Peter Iversen; Hermann Brenner; Katarina Cuk; Bernd Holleczek; Christiane Maier; Manuel Luedeke; Thomas Schnoeller; Jeri Kim; Christopher J Logothetis; Esther M John; Manuel R Teixeira; Paula Paulo; Marta Cardoso; Susan L Neuhausen; Linda Steele; Yuan Chun Ding; Kim De Ruyck; Gert De Meerleer; Piet Ost; Azad Razack; Jasmine Lim; Soo-Hwang Teo; Daniel W Lin; Lisa F Newcomb; Davor Lessel; Marija Gamulin; Tomislav Kulis; Radka Kaneva; Nawaid Usmani; Sandeep Singhal; Chavdar Slavov; Vanio Mitev; Matthew Parliament; Frank Claessens; Steven Joniau; Thomas Van den Broeck; Samantha Larkin; Paul A Townsend; Claire Aukim-Hastie; Manuela Gago-Dominguez; Jose Esteban Castelao; Maria Elena Martinez; Monique J Roobol; Guido Jenster; Ron H N van Schaik; Florence Menegaux; Thérèse Truong; Yves Akoli Koudou; Jianfeng Xu; Kay-Tee Khaw; Lisa Cannon-Albright; Hardev Pandha; Agnieszka Michael; Stephen N Thibodeau; Shannon K McDonnell; Daniel J Schaid; Sara Lindstrom; Constance Turman; Jing Ma; David J Hunter; Elio Riboli; Afshan Siddiq; Federico Canzian; Laurence N Kolonel; Loic Le Marchand; Robert N Hoover; Mitchell J Machiela; Zuxi Cui; Peter Kraft; Christopher I Amos; David V Conti; Douglas F Easton; Fredrik Wiklund; Stephen J Chanock; Brian E Henderson; Zsofia Kote-Jarai; Christopher A Haiman; Rosalind A Eeles Journal: Nat Genet Date: 2018-06-11 Impact factor: 38.330
Authors: H Ballentine Carter; Brian Helfand; Mufaddal Mamawala; Yishuo Wu; Patricia Landis; Hongjie Yu; Kathleen Wiley; Rong Na; Zhuqing Shi; Jacqueline Petkewicz; Sameep Shah; Richard J Fantus; Kristian Novakovic; Charles B Brendler; S Lilly Zheng; William B Isaacs; Jianfeng Xu Journal: Eur Urol Date: 2018-10-08 Impact factor: 20.096
Authors: A Karim Kader; Jielin Sun; Brian H Reck; Paul J Newcombe; Seong-Tae Kim; Fang-Chi Hsu; Ralph B D'Agostino; Sha Tao; Zheng Zhang; Aubrey R Turner; Greg T Platek; Colin F Spraggs; John C Whittaker; Brian R Lane; William B Isaacs; Deborah A Meyers; Eugene R Bleecker; Frank M Torti; Jeffery M Trent; John D McConnell; S Lilly Zheng; Lynn D Condreay; Roger S Rittmaster; Jianfeng Xu Journal: Eur Urol Date: 2012-05-12 Impact factor: 20.096
Authors: David V Conti; Burcu F Darst; Lilit C Moss; Edward J Saunders; Xin Sheng; Alisha Chou; Fredrick R Schumacher; Ali Amin Al Olama; Sara Benlloch; Tokhir Dadaev; Mark N Brook; Ali Sahimi; Thomas J Hoffmann; Atushi Takahashi; Koichi Matsuda; Yukihide Momozawa; Masashi Fujita; Kenneth Muir; Artitaya Lophatananon; Peggy Wan; Loic Le Marchand; Lynne R Wilkens; Victoria L Stevens; Susan M Gapstur; Brian D Carter; Johanna Schleutker; Teuvo L J Tammela; Csilla Sipeky; Anssi Auvinen; Graham G Giles; Melissa C Southey; Robert J MacInnis; Cezary Cybulski; Dominika Wokołorczyk; Jan Lubiński; David E Neal; Jenny L Donovan; Freddie C Hamdy; Richard M Martin; Børge G Nordestgaard; Sune F Nielsen; Maren Weischer; Stig E Bojesen; Martin Andreas Røder; Peter Iversen; Jyotsna Batra; Suzanne Chambers; Leire Moya; Lisa Horvath; Judith A Clements; Wayne Tilley; Gail P Risbridger; Henrik Gronberg; Markus Aly; Robert Szulkin; Martin Eklund; Tobias Nordström; Nora Pashayan; Alison M Dunning; Maya Ghoussaini; Ruth C Travis; Tim J Key; Elio Riboli; Jong Y Park; Thomas A Sellers; Hui-Yi Lin; Demetrius Albanes; Stephanie J Weinstein; Lorelei A Mucci; Edward Giovannucci; Sara Lindstrom; Peter Kraft; David J Hunter; Kathryn L Penney; Constance Turman; Catherine M Tangen; Phyllis J Goodman; Ian M Thompson; Robert J Hamilton; Neil E Fleshner; Antonio Finelli; Marie-Élise Parent; Janet L Stanford; Elaine A Ostrander; Milan S Geybels; Stella Koutros; Laura E Beane Freeman; Meir Stampfer; Alicja Wolk; Niclas Håkansson; Gerald L Andriole; Robert N Hoover; Mitchell J Machiela; Karina Dalsgaard Sørensen; Michael Borre; William J Blot; Wei Zheng; Edward D Yeboah; James E Mensah; Yong-Jie Lu; Hong-Wei Zhang; Ninghan Feng; Xueying Mao; Yudong Wu; Shan-Chao Zhao; Zan Sun; Stephen N Thibodeau; Shannon K McDonnell; Daniel J Schaid; Catharine M L West; Neil Burnet; Gill Barnett; Christiane Maier; Thomas Schnoeller; Manuel Luedeke; Adam S Kibel; Bettina F Drake; Olivier Cussenot; Géraldine Cancel-Tassin; Florence Menegaux; Thérèse Truong; Yves Akoli Koudou; Esther M John; Eli Marie Grindedal; Lovise Maehle; Kay-Tee Khaw; Sue A Ingles; Mariana C Stern; Ana Vega; Antonio Gómez-Caamaño; Laura Fachal; Barry S Rosenstein; Sarah L Kerns; Harry Ostrer; Manuel R Teixeira; Paula Paulo; Andreia Brandão; Stephen Watya; Alexander Lubwama; Jeannette T Bensen; Elizabeth T H Fontham; James Mohler; Jack A Taylor; Manolis Kogevinas; Javier Llorca; Gemma Castaño-Vinyals; Lisa Cannon-Albright; Craig C Teerlink; Chad D Huff; Sara S Strom; Luc Multigner; Pascal Blanchet; Laurent Brureau; Radka Kaneva; Chavdar Slavov; Vanio Mitev; Robin J Leach; Brandi Weaver; Hermann Brenner; Katarina Cuk; Bernd Holleczek; Kai-Uwe Saum; Eric A Klein; Ann W Hsing; Rick A Kittles; Adam B Murphy; Christopher J Logothetis; Jeri Kim; Susan L Neuhausen; Linda Steele; Yuan Chun Ding; William B Isaacs; Barbara Nemesure; Anselm J M Hennis; John Carpten; Hardev Pandha; Agnieszka Michael; Kim De Ruyck; Gert De Meerleer; Piet Ost; Jianfeng Xu; Azad Razack; Jasmine Lim; Soo-Hwang Teo; Lisa F Newcomb; Daniel W Lin; Jay H Fowke; Christine Neslund-Dudas; Benjamin A Rybicki; Marija Gamulin; Davor Lessel; Tomislav Kulis; Nawaid Usmani; Sandeep Singhal; Matthew Parliament; Frank Claessens; Steven Joniau; Thomas Van den Broeck; Manuela Gago-Dominguez; Jose Esteban Castelao; Maria Elena Martinez; Samantha Larkin; Paul A Townsend; Claire Aukim-Hastie; William S Bush; Melinda C Aldrich; Dana C Crawford; Shiv Srivastava; Jennifer C Cullen; Gyorgy Petrovics; Graham Casey; Monique J Roobol; Guido Jenster; Ron H N van Schaik; Jennifer J Hu; Maureen Sanderson; Rohit Varma; Roberta McKean-Cowdin; Mina Torres; Nicholas Mancuso; Sonja I Berndt; Stephen K Van Den Eeden; Douglas F Easton; Stephen J Chanock; Michael B Cook; Fredrik Wiklund; Hidewaki Nakagawa; John S Witte; Rosalind A Eeles; Zsofia Kote-Jarai; Christopher A Haiman Journal: Nat Genet Date: 2021-01-04 Impact factor: 38.330
Authors: Jianfeng Xu; W Kyle Resurreccion; Zhuqing Shi; Jun Wei; Chi-Hsiung Wang; S Lilly Zheng; Peter J Hulick; Ashley E Ross; Christian P Pavlovich; Brian T Helfand; William B Isaacs Journal: Prostate Cancer Prostatic Dis Date: 2022-03-28 Impact factor: 5.455
Authors: Yu Jiang; Travis J Meyers; Adaeze A Emeka; Lauren Folgosa Cooley; Phillip R Cooper; Nicola Lancki; Irene Helenowski; Linda Kachuri; Daniel W Lin; Janet L Stanford; Lisa F Newcomb; Suzanne Kolb; Antonio Finelli; Neil E Fleshner; Maria Komisarenko; James A Eastham; Behfar Ehdaie; Nicole Benfante; Christopher J Logothetis; Justin R Gregg; Cherie A Perez; Sergio Garza; Jeri Kim; Leonard S Marks; Merdie Delfin; Danielle Barsa; Danny Vesprini; Laurence H Klotz; Andrew Loblaw; Alexandre Mamedov; S Larry Goldenberg; Celestia S Higano; Maria Spillane; Eugenia Wu; H Ballentine Carter; Christian P Pavlovich; Mufaddal Mamawala; Tricia Landis; Peter R Carroll; June M Chan; Matthew R Cooperberg; Janet E Cowan; Todd M Morgan; Javed Siddiqui; Rabia Martin; Eric A Klein; Karen Brittain; Paige Gotwald; Daniel A Barocas; Jeremiah R Dallmer; Jennifer B Gordetsky; Pam Steele; Shilajit D Kundu; Jazmine Stockdale; Monique J Roobol; Lionne D F Venderbos; Martin G Sanda; Rebecca Arnold; Dattatraya Patil; Christopher P Evans; Marc A Dall'Era; Anjali Vij; Anthony J Costello; Ken Chow; Niall M Corcoran; Soroush Rais-Bahrami; Courtney Phares; Douglas S Scherr; Thomas Flynn; R Jeffrey Karnes; Michael Koch; Courtney Rose Dhondt; Joel B Nelson; Dawn McBride; Michael S Cookson; Kelly L Stratton; Stephen Farriester; Erin Hemken; Walter M Stadler; Tuula Pera; Deimante Banionyte; Fernando J Bianco; Isabel H Lopez; Stacy Loeb; Samir S Taneja; Nataliya Byrne; Christopher L Amling; Ann Martinez; Luc Boileau; Franklin D Gaylis; Jacqueline Petkewicz; Nicholas Kirwen; Brian T Helfand; Jianfeng Xu; Denise M Scholtens; William J Catalona; John S Witte Journal: HGG Adv Date: 2021-11-19
Authors: Rocco S Flammia; Benedikt Hoeh; Lukas Hohenhorst; Gabriele Sorce; Francesco Chierigo; Andrea Panunzio; Zhe Tian; Fred Saad; Costantino Leonardo; Alberto Briganti; Alessandro Antonelli; Carlo Terrone; Shahrokh F Shariat; Umberto Anceschi; Markus Graefen; Felix K H Chun; Francesco Montorsi; Michele Gallucci; Pierre I Karakiewicz Journal: Int Urol Nephrol Date: 2022-07-15 Impact factor: 2.266