(ChemotherapyAdvisor) – The first large-scale Genome-Wide Association Study to identify single nucleotide polymorphisms (SNPs) associated with development for erectile dysfunction (ED) among prostate cancer patients treated with radiation therapy has identified 12 genetic markers of risk, investigators reported in the International Journal of Radiation Oncology • Biology • Physics online September 26.
“Prostate cancer screening and treatment are undergoing major shifts,” said Harry Ostrer, MD, of Albert Einstein College of Medicine of Yeshiva University and Director of Genetic and Genomic Testing at Montefiore Medical Center and coprincipal investigator of the study, which included a research team from Mount Sinai School of Medicine, New York.
“This is part of our ongoing effort to identify men at highest risk for disease, identify the aggressive tumors that would be responsive to therapy, and to improve quality of life for men with indolent prostate cancers who might benefit from active surveillance, rather than therapy.”
The study randomly split patients into a discovery cohort of 132 cases (men with prostate cancer who developed ED following radiation therapy) and 103 controls. The 940 top-ranking SNPs genotyped from this cohort were regenotyped and validated in a replication cohort of 128 cases and 102 controls.
Of the 940 SNPs, 12 were associated with development of ED following radiation therapy. “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,” they reported. “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.”
To determine which SNPs to include as part of a screening test to identify men with prostate cancer at greatest risk for developing ED following radiation therapy, “these candidate genetic predictors warrant more definitive validation in an independent cohort,” they stated.
The study was supported by the American Cancer Society, the US Department of Defense, and the National Institutes of Health.