BACKGROUND: Prostate cancer is associated with defective DNA strand break repair after DNA damage leading to genetic instability and prostate cancer progression. The ATM (ataxia-telangiectasia mutated) gene product is known to play an important role in cell cycle regulation and maintenance of genomic integrity. We investigated whether the prevalence of the ATM missense substitution P1054R is increased in a hospital-based series of prostate cancer patients and whether carriers are at increased risk for treatment-related side effects. MATERIALS AND METHODS: A consecutive series of 261 patients treated for early-stage prostate cancer with I-125 brachytherapy (permanent seed implantation) between 10/2000 and 04/2006 at our institution and a comparison group of 460 male control individuals were screened for the presence of the P1054R variant. Outcome of therapy regarding morbidity was assessed prospectively and compared between carriers vs. non-carriers with the International Prostate Symptom Score (IPSS), a Quality-of-Life-index (QoL) and the International Index of Erectile Function (IIEF-15) with its subgroups (IIEF-5 and EF). RESULTS: The proportion of carriers of the P1054R variant was significantly higher among prostate cancer patients than in the general population (25 out of 261 vs. 22 out of 460; OR 2.1; 95% CI 1.2-3.8, p<0.01). A subgroup of the carriers additionally harboured the ATM missense variant F858L that was associated with a similar risk (OR=2.2; 95% CI 1.1-4.6; p=0.03). After a mean follow-up of 18 months there were no statistically significant differences regarding IPSS (p=0.48), QoL (p=0.61), IIEF-15 score (p=0.78), IIEF-5 score (p=0.83), and EF score (p=0.80), respectively. CONCLUSIONS: The ATM missense variant P1054R confers an about twofold increased risk for prostate cancer in our series. The subgroup of patients with the second-site variant F858L is not at significantly higher risk. After 18 months, there was no evidence for an increased adverse radiotherapy response in P1054R carriers.
BACKGROUND:Prostate cancer is associated with defective DNA strand break repair after DNA damage leading to genetic instability and prostate cancer progression. The ATM (ataxia-telangiectasia mutated) gene product is known to play an important role in cell cycle regulation and maintenance of genomic integrity. We investigated whether the prevalence of the ATM missense substitution P1054R is increased in a hospital-based series of prostate cancerpatients and whether carriers are at increased risk for treatment-related side effects. MATERIALS AND METHODS: A consecutive series of 261 patients treated for early-stage prostate cancer with I-125 brachytherapy (permanent seed implantation) between 10/2000 and 04/2006 at our institution and a comparison group of 460 male control individuals were screened for the presence of the P1054R variant. Outcome of therapy regarding morbidity was assessed prospectively and compared between carriers vs. non-carriers with the International Prostate Symptom Score (IPSS), a Quality-of-Life-index (QoL) and the International Index of Erectile Function (IIEF-15) with its subgroups (IIEF-5 and EF). RESULTS: The proportion of carriers of the P1054R variant was significantly higher among prostate cancerpatients than in the general population (25 out of 261 vs. 22 out of 460; OR 2.1; 95% CI 1.2-3.8, p<0.01). A subgroup of the carriers additionally harboured the ATM missense variant F858L that was associated with a similar risk (OR=2.2; 95% CI 1.1-4.6; p=0.03). After a mean follow-up of 18 months there were no statistically significant differences regarding IPSS (p=0.48), QoL (p=0.61), IIEF-15 score (p=0.78), IIEF-5 score (p=0.83), and EF score (p=0.80), respectively. CONCLUSIONS: The ATM missense variant P1054R confers an about twofold increased risk for prostate cancer in our series. The subgroup of patients with the second-site variant F858L is not at significantly higher risk. After 18 months, there was no evidence for an increased adverse radiotherapy response in P1054R carriers.
Authors: Li Xu; Elaine Cristina Morari; Qingyi Wei; Erich M Sturgis; Laura S Ward Journal: J Clin Endocrinol Metab Date: 2012-03-21 Impact factor: 5.958
Authors: Andreas Meyer; Thilo Dörk; Natalia Bogdanova; Maria-Jantje Brinkhaus; Birgitt Wiese; Jörn Hagemann; Jürgen Serth; Michael Bremer; Rolf Baumann; Johann H Karstens; Stefan Machtens Journal: World J Urol Date: 2008-11-28 Impact factor: 4.226
Authors: Jinyun Chen; Mala Pande; Yu-Jing Huang; Chongjuan Wei; Christopher I Amos; Bente A Talseth-Palmer; Cliff J Meldrum; Wei V Chen; Ivan P Gorlov; Patrick M Lynch; Rodney J Scott; Marsha L Frazier Journal: Carcinogenesis Date: 2012-11-03 Impact factor: 4.944
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: Veda N Giri; Karen E Knudsen; William K Kelly; Heather H Cheng; Kathleen A Cooney; Michael S Cookson; William Dahut; Scott Weissman; Howard R Soule; Daniel P Petrylak; Adam P Dicker; Saud H AlDubayan; Amanda E Toland; Colin C Pritchard; Curtis A Pettaway; Mary B Daly; James L Mohler; J Kellogg Parsons; Peter R Carroll; Robert Pilarski; Amie Blanco; Ashley Woodson; Alanna Rahm; Mary-Ellen Taplin; Thomas J Polascik; Brian T Helfand; Colette Hyatt; Alicia K Morgans; Felix Feng; Michael Mullane; Jacqueline Powers; Raoul Concepcion; Daniel W Lin; Richard Wender; James Ryan Mark; Anthony Costello; Arthur L Burnett; Oliver Sartor; William B Isaacs; Jianfeng Xu; Jeffrey Weitzel; Gerald L Andriole; Himisha Beltran; Alberto Briganti; Lindsey Byrne; Anne Calvaresi; Thenappan Chandrasekar; David Y T Chen; Robert B Den; Albert Dobi; E David Crawford; James Eastham; Scott Eggener; Matthew L Freedman; Marc Garnick; Patrick T Gomella; Nathan Handley; Mark D Hurwitz; Joseph Izes; R Jeffrey Karnes; Costas Lallas; Lucia Languino; Stacy Loeb; Ana Maria Lopez; Kevin R Loughlin; Grace Lu-Yao; S Bruce Malkowicz; Mark Mann; Patrick Mille; Martin M Miner; Todd Morgan; Jose Moreno; Lorelei Mucci; Ronald E Myers; Sarah M Nielsen; Brock O'Neil; Wayne Pinover; Peter Pinto; Wendy Poage; Ganesh V Raj; Timothy R Rebbeck; Charles Ryan; Howard Sandler; Matthew Schiewer; E Michael D Scott; Brittany Szymaniak; William Tester; Edouard J Trabulsi; Neha Vapiwala; Evan Y Yu; Charnita Zeigler-Johnson; Leonard G Gomella Journal: J Clin Oncol Date: 2020-06-09 Impact factor: 44.544