A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of urinary symptoms after radiotherapy for prostate cancer. J Urol 2013 Jul;190(1):102-8
Date
02/05/2013Pubmed ID
23376709DOI
10.1016/j.juro.2013.01.096Scopus ID
2-s2.0-84878825562 (requires institutional sign-in at Scopus site) 52 CitationsAbstract
PURPOSE: We identified single nucleotide polymorphisms associated with change in the AUA Symptom Score after radiotherapy for prostate cancer.
MATERIALS AND METHODS: A total of 723 patients treated with brachytherapy with or without external beam radiation therapy were assessed at baseline and annually after radiotherapy using the AUA Symptom Score. A 2-stage genome-wide association study was performed with the primary end point of change in AUA Symptom Score from baseline at each of 4 followup periods. Single nucleotide polymorphism associations were assessed using multivariable linear regression adjusting for pre-radiotherapy AUA Symptom Score 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 single nucleotide polymorphisms showed the strongest association with change in AUA Symptom Score (combined p values 8.8×10(-6) to 6.5×10(-7) at 2 to 3 years after radiotherapy). These single nucleotide polymorphisms form a haplotype block that encompasses the inflammation signaling gene IFNK. These single nucleotide polymorphisms were independently associated with change in AUA Symptom Score after adjusting for clinical predictors including smoking history, hypertension, α-blocker use and pre-radiotherapy AUA Symptom Score. An additional 24 single nucleotide polymorphisms showed moderate significance for association with change in AUA Symptom Score. Several of these single nucleotide polymorphisms were more strongly associated with change in specific AUA Symptom Score items, including rs13035033 in the MYO3B gene, which was associated with straining (beta coefficient 0.9, 95% CI 0.6-1.2, p = 5.0×10(-9)).
CONCLUSIONS: If validated, these single nucleotide polymorphisms could provide insight into the biology underlying urinary symptoms following radiotherapy and could lead to development of an assay to identify patients at risk for experiencing these effects.
Author List
Kerns SL, Stone NN, Stock RG, Rath L, Ostrer H, Rosenstein BSAuthor
Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Age DistributionAged
Analysis of Variance
Brachytherapy
Chi-Square Distribution
Cohort Studies
Confidence Intervals
Follow-Up Studies
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Incidence
Male
Middle Aged
Neoplasm Invasiveness
Neoplasm Staging
Polymorphism, Single Nucleotide
Prostatic Neoplasms
Risk Assessment
Urologic Diseases