Association between single nucleotide polymorphisms and the development of erectile dysfunction in African-American men treated with radiotherapy for prostate cancer

B79

The purpose of this study was to determine whether the possession of variants in genes that encode proteins associated with responses to radiation is correlated with the development of erectile (ED) dysfunction in African-American prostate cancer patients treated with radiotherapy. 144 patients with a median follow-up time of 28 months who self-identified as being African American and underwent definitive radiotherapy for prostate cancer were comprehensively screened for single nucleotide polymorphisms (SNPs) in ATM, TGFB1, SOD2, XRCC1, XRCC3, and RAD21 using either denaturing high performance liquid chromatography or the Surveyor nuclease assay. The Mount Sinai Erectile Function Scale was used to determine whether a patient developed ED after radiotherapy as defined by a prospective decline in erectile function. In this system, ED is physician assessed using a score of; 0-complete inability to achieve an erection, 1-able to achieve erections but insufficient for intercourse, 2-can achieve erections sufficient for intercourse but considered suboptimal and 3-normal erectile function. A drop of two points on this scale from the pre- to post-treatment score constituted a prospective decline in erectile function and represented ED. Using these criteria, 35 men exhibited ED following radiotherapy whereas the remaining 109 screened subjects did not. Odds ratios (ORs) ≥2 for the development of ED were obtained for patients possessing the following SNPs; 1254 A→G in ATM; 1625 T→C, IVS5+8 G→A or 1427 T→G in RAD21; 964 G→A or 1852 A→C in XRCC1; 1075 C→T (homozygous) or 634 G→A in XRCC3; 47 T→C (homozygous) in SOD2. Although these values did not reach statistical significance by themselves, it was found that patients possessing either 0, 1, 2 or ≥3 of these “radiosensitivity” SNPs had ORs (95% confidence interval) for a prospective decline in erectile function of 0.03 (0.01-0.12), 0.9 (0.3-3.0), 1.9 (0.8-4.5) and 4.4 (1.4-13.0). Although the results of this study will need to be validated through screening a second comparable group of subjects in a replication study, our results suggest that possession of multiple SNPs in the ATM, SOD2, XRCC1, XRCC3 and RAD21 genes is associated with the development of ED among African-American prostate cancer patients treated with radiotherapy. Most striking, patients that did not have any “radiosensitivty” SNPs, rarely developed ED following radiotherapy. In contrast, men that had ≥3 of these SNPs, displayed a substantially elevated risk for the development of ED following radiation treatment for prostate cancer. The results of this study may provide a basis for a predictive assay to identify which African-American men are at greatest risk for the development of ED following radiotherapy for prostate cancer. This work was supported by grant RSGT-05-200-01-CCE from the American Cancer Society.