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A 2-Stage Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms Associated with Development of Urinary Symptoms After Radiotherapy for Prostate Cancer

2013; Lippincott Williams & Wilkins; Volume: 190; Issue: 1 Linguagem: Inglês

10.1016/j.juro.2013.01.096

1527-3792

Sarah L. Kerns, Nelson N. Stone, Richard G. Stock, Lynda Rath, Harry Ostrer, Barry S. Rosenstein,

Liver Disease Diagnosis and Treatment

No AccessJournal of UrologyAdult Urology1 Jul 2013A 2-Stage Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms Associated with Development of Urinary Symptoms After Radiotherapy for Prostate Cancer Sarah L. Kerns, Nelson N. Stone, Richard G. Stock, Lynda Rath, Harry Ostrer, and Barry S. Rosenstein Sarah L. KernsSarah L. Kerns Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York Departments of Pathology and Genetics, Albert Einstein College of Medicine, New York, New York , Nelson N. StoneNelson N. Stone Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York Department of Urology, Mount Sinai School of Medicine, New York, New York , Richard G. StockRichard G. Stock Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York , Lynda RathLynda Rath Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York , Harry OstrerHarry Ostrer Departments of Pathology and Genetics, Albert Einstein College of Medicine, New York, New York , and Barry S. RosensteinBarry S. Rosenstein Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York Department of Dermatology and Preventive Medicine, Mount Sinai School of Medicine, New York, New York Department of Radiation Oncology, New York University School of Medicine, New York, New York View All Author Informationhttps://doi.org/10.1016/j.juro.2013.01.096AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We identified single nucleotide polymorphisms associated with change in the AUA Symptom Score after radiotherapy for prostate cancer. Materials and Methods: A total of 723 patients treated with brachytherapy with or without external beam radiation therapy were assessed at baseline and annually after radiotherapy using the AUA Symptom Score. A 2-stage genome-wide association study was performed with the primary end point of change in AUA Symptom Score from baseline at each of 4 followup periods. Single nucleotide polymorphism associations were assessed using multivariable linear regression adjusting for pre-radiotherapy AUA Symptom Score severity category and clinical variables. Fisher's trend method was used to calculate combined p values from the discovery and replication cohorts. Results: A region on chromosome 9p21.2 containing 8 single nucleotide polymorphisms showed the strongest association with change in AUA Symptom Score (combined p values 8.8×10−6 to 6.5×10−7 at 2 to 3 years after radiotherapy). These single nucleotide polymorphisms form a haplotype block that encompasses the inflammation signaling gene IFNK. These single nucleotide polymorphisms were independently associated with change in AUA Symptom Score after adjusting for clinical predictors including smoking history, hypertension, α-blocker use and pre-radiotherapy AUA Symptom Score. An additional 24 single nucleotide polymorphisms showed moderate significance for association with change in AUA Symptom Score. Several of these single nucleotide polymorphisms were more strongly associated with change in specific AUA Symptom Score items, including rs13035033 in the MYO3B gene, which was associated with straining (beta coefficient 0.9, 95% CI 0.6–1.2, p = 5.0×10−9). Conclusions: If validated, these single nucleotide polymorphisms could provide insight into the biology underlying urinary symptoms following radiotherapy and could lead to development of an assay to identify patients at risk for experiencing these effects. 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Google Scholar 21 : Urinary symptom flare following I-125 prostate brachytherapy. Int J Radiat Oncol Biol Phys2003; 56: 1085. Google Scholar © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited bySteers W (2018) This Month in Adult UrologyJournal of Urology, VOL. 190, NO. 1, (1-2), Online publication date: 1-Jul-2013. Volume 190Issue 1July 2013Page: 102-108Supplementary Materials Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Keywordsgenome-wide association studyprostatic neoplasmsmorbidityradiotherapyMetricsAuthor Information Sarah L. Kerns Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York Departments of Pathology and Genetics, Albert Einstein College of Medicine, New York, New York More articles by this author Nelson N. Stone Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York Department of Urology, Mount Sinai School of Medicine, New York, New York Financial interest and/or other relationship with Myriad Genetics, Amgen, DCMI and PCEC. More articles by this author Richard G. Stock Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York Financial interest and/or other relationship with Bard. More articles by this author Lynda Rath Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York More articles by this author Harry Ostrer Departments of Pathology and Genetics, Albert Einstein College of Medicine, New York, New York Equal study contribution. More articles by this author Barry S. Rosenstein Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York Department of Dermatology and Preventive Medicine, Mount Sinai School of Medicine, New York, New York Department of Radiation Oncology, New York University School of Medicine, New York, New York Equal study contribution. More articles by this author Expand All Advertisement PDF downloadLoading ...