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SNPs identified for radiation-associated erectile dysfunction
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Twelve single nucleotide polymorphisms were associated with erectile dysfunction in a cohort of men with prostate cancer treated with radiation, according to study results.
The two-stage genome-wide association study included a stage 1 discovery cohort that involved 132 patients and 103 controls. The stage 2 replication cohort involved 128 cases and 102 controls.
The researchers selected 940 top-ranking SNPs from the discovery group and replicated them in the replication cohort.
Twelve SNPs identified in the discovery stage and validated in the replication stage demonstrated links to radiation-associated erectile dysfunction (Fisher combined P=2.1×10−5 to 6.2×10−4).
“Thankfully, current treatments for prostate cancer offer excellent rates of long-term survival, so patients and their physicians have a choice about which treatment path to take,” Barry Rosenstein, PhD, professor of radiation oncology at Mount Sinai School of Medicine, said in a press release. “However, the risk of developing erectile dysfunction after radiation treatment is highly variable, suggesting there may be a genetic component to determining that risk. Our study confirms that specific markers make certain patients more susceptible to this side effect.”
The 12 SNPs lie in or near genes involved in erectile function or other normal cellular functions such as adhesion and signaling, according to researchers. They do not lie near DNA damage repair.
Results of a multivariate analysis that included non-genetic risk factors demonstrated an OR for these SNPs of 1.6 to 5.6 in a pooled cohort.
The cumulative number of SNP risk alleles in individual patients was strongly associated with erectile dysfunction status (Sommers’ D P=1.7×10−29).
The risk for erectile dysfunction increased by a factor of 2.2 with a one-allele increase in cumulative SNP score (P=2.1×10−19).
Researchers observed a sensitivity of 84% and a specificity of 75% for the cumulative SNP score model as a prognostic factor for the development of erectile dysfunction during radiation.
Harry Ostrer
These candidate genetic predictors warrant more definitive validation in an independent cohort, the researchers concluded.
“Prostate cancer screening and treatment are undergoing major shifts,” Harry Ostrer, MD, professor of pathology and genetics at Albert Einstein College of Medicine and director of genetic and genomic testing at Montefiore Medical Center, said in a press release. “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.”