A 2-Stage Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms Associated With Development of Erectile Dysfunction Following Radiation Therapy for Prostate Cancer

作者：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^*

来源：International Journal of Radiation Oncology, Biology, Physics, 2013, 85(1): E21-E28.

DOI：10.1016/j.ijrobp.2012.08.003

Purpose: To identify single nucleotide polymorphisms (SNPs) associated with development of erectile dysED) among prostate cancer patients treated with radiation therapy. %26lt;br%26gt;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. %26lt;br%26gt;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 x 10(-5) to 6.2 x 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%26apos; D P value = 1.7 x 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 x 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. %26lt;br%26gt;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.

• 出版日期2013-1-1