PURPOSE: To identify SNPs associated with change in American Urological Association Symptom Score (AUASS) following radiotherapy (RT) for prostate cancer.
MATERIALS AND METHODS: 723 patients treated with brachytherapy with or without external beam radiation therapy were assessed at baseline and annually after RT using the AUASS. A two-stage genome-wide association study was performed with the primary endpoint of change in AUASS from baseline at each of four follow-up periods. SNP associations were assessed using multivariable linear regression adjusting for pre-RT AUASS severity category and clinical variables. Fisher's trend method was used to calculate combined p-values from the discovery and replication cohorts.
RESULTS: A region on chromosome 9p21.2 containing 8 SNPs showed the strongest association with change in AUASS (combined p-values 8.8x10-6 to 6.5x10-7 at 2-3 years post-RT). These SNPs form a haplotype block that is associated with change in AUASS and encompasses the inflammation signaling gene IFNK. These SNPs were independently associated with change in AUASS after adjusting for clinical predictors including smoking history, hypertension, alpha-blocker use, and pre-RT AUASS. An additional 24 SNPs showed moderate significance for association with change in AUASS. Several of these SNPs were more strongly associated with change in specific AUASS items, including rs13035033 in the MYO3B gene, which was associated with straining (beta coefficient = 0.9, 95%CI 0.6-1.2; p-value = 5.0x10-9).
CONCLUSIONS: If validated, these SNPs could provide insight into the biology underlying urinary symptoms following RT and could lead to development of an assay to identify patients at risk for experiencing these effects.
Written by:
Kerns SL, Stone NN, Stock RG, Rath L, Ostrer H, Rosenstein BS. Are you the author?
Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY; Departments of Pathology and Genetics, Albert Einstein College of Medicine, Bronx, NY.
Reference: J Urol. 2013 Jan 31. pii: S0022-5347(13)00240-1.
doi: 10.1016/j.juro.2013.01.096
PubMed Abstract
PMID: 23376709
UroToday.com Investigative Urology Section
