A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of urinary symptoms after radiotherapy for prostate cancer.

PURPOSE:We identified single nucleotide polymorphisms associated with change in the AUA Symptom 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 A 2-stage genome-wide association study was performed with the primary end point of change in AUA Symptom duanyu1845 from baseline at each of 4 followup periods. Single nucleotide polymorphism associations were assessed using multivariable linear regression adjusting for pre-radiotherapy AUA Symptom duanyu1845 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 duanyu1845 (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 duanyu1845 after adjusting for clinical predictors including smoking history, hypertension, α-blocker use and pre-radiotherapy AUA Symptom duanyu1845. An additional 24 single nucleotide polymorphisms showed moderate significance for association with change in AUA Symptom duanyu1845. Several of these single nucleotide polymorphisms were more strongly associated with change in specific AUA Symptom duanyu1845 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.

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