DNA Patterns May Predict ED After Radiation (CME/CE)

Authors: MedPage Today

By Michael Smith, North American Correspondent, MedPage Today
Published: September 27, 2012
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

A suite of 12 genetic variations may help doctors determine who will have erectile dysfunction after radiation therapy for prostate cancer, researchers reported.

In a two-step genome-wide association study, the 12 variants were found to lie in or near genes involved in erectile function and other normal cellular functions, according to Barry Rosenstein, PhD, of Mount Sinai Medical School in New York City, and colleagues.

And the risk of erectile dysfunction rose significantly in men with more of the 12 variants, Rosenstein and colleagues reported online in the Oct. 1 issue of International Journal of Radiation Oncology - Biology - Physics.

The researchers cautioned that further validation is needed, because none of the variants – single-nucleotide polymorphisms (SNPs) – reached the usual benchmark for genome-wide statistical significance.

But if they are validated in future studies, Rosenstein said in a statement "these SNPs could provide the basis for a blood test that would enable radiation oncologists to predict more accurately which men are most likely to develop erectile dysfunction after prostate cancer radiation therapy."

The findings come from analysis of outcomes for 593 men treated at two centers with radiation – either brachytherapy, brachytherapy combined with external-beam radiation, or external-beam radiation alone.

The patients were divided into a discovery and a validation cohort and again into cases and controls, based on scores on the Sexual Health Inventory for Men (or SHIM) questionnaire.

All 593 men were potent, defined as a SHIM score of at least 16, before the radiation treatment and they were followed every 3 to 6 months afterward.

For this analysis, cases were those with at least one SHIM score of 7 or lower – defined as "severe" erectile dysfunction – between 1 and 5 years after therapy, while controls were those whose SHIM scores were always 16 or higher.

In total, there were 260 cases and 205 controls, Rosenstein and colleagues reported. The discovery cohort included 132 cases and 103 controls, while the validation cohort had 128 cases and 102 controls.

Analysis showed that patients in the case cohort were older, more likely to have undergone androgen deprivation therapy, had a larger prostate volume at the time of radiation treatment, and were more likely to have had combined brachytherapy and external-beam radiation.

In the discovery cohort, genetic analysis found 940 SNPs that were significantly different between cases and controls (P-values ranging from 8x10-4 to 2x10-6).

In the validation cohort, that number was reduced to the 12 SNPs that were most "robustly associated" with increased risk of erectile dysfunction, the authors reported.

In the full cohort, a multivariate analysis showed that after controlling for clinical factors, all 12 SNPs had odds ratios for increased risk ranging from 1.6 to 5.6, suggesting they "represent clinically relevant predictors," Rosenstein and colleagues argued.

After controlling for clinical factors and ancestry, each additional risk allele carried by one of the participants increased his risk of erectile dysfunction by a factor of 2.2 (95% CI 1.9 to 2.6, P=2.1x10-19).

The researchers cautioned that data on comorbidities was limited, adding it's possible that worsening comorbidities could have accounted for some of the risk of erectile dysfunction.

The study had support from the American Cancer Society, the U.S. Department of Defense, and the NIH. The journal said Rosenstein had no financial conflicts of interest.

Primary source: International Journal of Radiation Oncology - Biology - Physics
Source reference:

Kerns SL, et al "A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of erectile dysfunction following radiation therapy for prostate cancer" Int J Radiation Oncol Biol Phys 2012; DOI: 10.1016/j.ijrobp.2012.08.003.

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