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Title: A 2-Stage Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms Associated With Development of Erectile Dysfunction Following Radiation Therapy for Prostate Cancer
Authors: Kerns, Sarah L ×
Stock, Richard
Stone, Nelson
Buckstein, Michael
Shao, Yongzhao
Campbell, Christopher
Rath, Lynda
De Ruysscher, Dirk
Lammering, Guido
Hixson, Rosetta
Cesaretti, Jamie
Terk, Mitchell
Ostrer, Harry
Rosenstein, Barry S #
Issue Date: Jan-2013
Publisher: Pergamon Press
Series Title: International Journal of Radiation Oncology, Biology, Physics vol:85 issue:1 pages:E21-E28
Article number: S0360-3016(12)03389-5
Abstract: PURPOSE: To identify single nucleotide polymorphisms (SNPs) associated with development of erectile dysfunction (ED) among prostate cancer patients treated with radiation therapy. METHODS AND MATERIALS: A 2-stage genome-wide association study was performed. Patients were split randomly into a stage I discovery cohort (132 cases, 103 controls) and a stage II replication cohort (128 cases, 102 controls). The discovery cohort was genotyped using Affymetrix 6.0 genome-wide arrays. The 940 top ranking SNPs selected from the discovery cohort were genotyped in the replication cohort using Illumina iSelect custom SNP arrays. RESULTS: Twelve SNPs identified in the discovery cohort and validated in the replication cohort were associated with development of ED following radiation therapy (Fisher combined P values 2.1 × 10(-5) to 6.2 × 10(-4)). Notably, these 12 SNPs lie in or near genes involved in erectile function or other normal cellular functions (adhesion and signaling) rather than DNA damage repair. In a multivariable model including nongenetic risk factors, the odds ratios for these SNPs ranged from 1.6 to 5.6 in the pooled cohort. There was a striking relationship between the cumulative number of SNP risk alleles an individual possessed and ED status (Sommers' D P value = 1.7 × 10(-29)). A 1-allele increase in cumulative SNP score increased the odds for developing ED by a factor of 2.2 (P value = 2.1 × 10(-19)). The cumulative SNP score model had a sensitivity of 84% and specificity of 75% for prediction of developing ED at the radiation therapy planning stage. CONCLUSIONS: This genome-wide association study identified a set of SNPs that are associated with development of ED following radiation therapy. These candidate genetic predictors warrant more definitive validation in an independent cohort.
ISSN: 0360-3016
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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