Faculty Collaboration Database

A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of erectile dysfunction following radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys 2013 Jan 01;85(1):e21-8

Date

10/02/2012

Pubmed ID

23021708

Pubmed Central ID

PMC3616619

DOI

10.1016/j.ijrobp.2012.08.003

Scopus ID

2-s2.0-84871377389 (requires institutional sign-in at Scopus site)   52 Citations

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.

Author List

Kerns SL, Stock R, Stone N, Buckstein M, Shao Y, Campbell C, Rath L, De Ruysscher D, Lammering G, Hixson R, Cesaretti J, Terk M, Ostrer H, Rosenstein BS

Author

Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Age Factors
Aged
Brachytherapy
Erectile Dysfunction
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Iodine Radioisotopes
Male
Middle Aged
Palladium
Polymorphism, Single Nucleotide
Prospective Studies
Prostatic Neoplasms
Radioisotopes
Radiotherapy, Conformal