Twelve genetic markers have been associated with the development of erectile dysfunction (ED) following radiation therapy (RT) for prostate cancer, according to a study published online Sept. 27 in the International Journal of Radiation Oncology• Biology• Physics.
Given the multitude of treatment options with excellent long-term survival rates for men with prostate cancer, morbidities and toxicities of various treatment strategies play a large role in the decision-making process. Although RT offers favorable maintenance of erectile function for many patients, there is significant variation in the development of ED among men treated with RT, which suggests genetic risk factors.
Sarah L. Kerns, PhD, MPH, of the department of radiation oncology at Mount Sinai School of Medicine in New York City, and colleagues designed a two-stage genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with the development of ED following RT for prostate cancer.
The researchers enrolled 233 patients in the Stage I discovery cohort, with 132 cases and 103 controls. The Stage II replication cohort consisted of 128 cases and 102 controls.
Kerns and colleagues administered the Sexual Health Inventory for Men or Mount Sinai Erectile Function questionnaires every three to six months. Patients were potent prior to treatment and had a minimum of one year follow-up. Cases were defined as “severe ED” by the survey instrument and controls were defined by “no” or “mild” ED.
The researchers genotyped DNA samples for more than 900,000 SNPs and found that 12 were associated with the development of ED after RT. “The ORs [odds ratios] for the individual SNPs ranges from 1.6 to 5.6 indicating that after controlling for clinical factors, the SNPs represent clinically relevant predictors of ED,” wrote Kerns et al.
Kerns and colleagues estimated a cumulative SNP score by combining the 12 SNPs. A one allele increase in the cumulative score raised the odds of developing ED by a factor of 2.2. They also stratified the cohort by age, using 62 years as a cutoff, and cumulative SNP, using nine as a cutoff. A total of 21.8 percent of younger men with nine or fewer alleles developed ED. Incidence of ED among younger men rose to 52.7 percent for those with more than nine alleles. The ED rate for older men with nine or fewer alleles was 54.8 percent and 92.5 percent for those with more than nine risk alleles.
The researchers tested the model in two independent, small cohorts, with results indicating the overall predictive power of the model.
Kerns and colleagues noted that future studies could identify additional predictive SNPs.