Genetic Sequence Variants Are Associated With Both Severity Of Lower Urinary Tract Symptoms And Prostate Cancer Susceptibility
Helfand BT, Hu Q, Loeb S, McVary KT, Catalona WJ. J Urol. 2012 Nov 13. pii: S0022-5347(12)05522-X. doi: 10.1016/j.juro.2012.11.044. [Epub ahead of print]


Division of Urology, Department of Surgery,NorthShore University Health System, Evanston, IL.


PURPOSE:: While there is a clear heritable component underlying lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH), few studies have identified specific genetic factors. In contrast, recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that increase prostate cancer (PCa) risk. Some of these SNPs may also predispose to surgical interventions for BPH. Our objective was to determine whether these SNPs also associate with LUTS severity and BPH medication use. METHODS AND MATERIALS:: The genotypes of 38 SNPs previously associated with PCa risk were determined for 1,168 healthy Caucasian male volunteers. Their AUA symptom index (AUA-SI) score and use of medications for BPH were documented prospectively. Statistical analyses compared the frequency of the SNPs with AUA-SI score and BPH medication use. RESULTS:: Several SNPs including rs2736098 on chromosome 5p15 showed a significant relationship with BPH medication use. After adjusting for the presence of the other genetic variants, age and medication use, rs1571801 on chromosome 9q33.2 (OR=1.31, 95% C.I.1.0-1.74) and rs5945572 on chromosome Xp11 (OR=1.28, 95% C.I. 1.04-1.59) were significantly associated with increased urinary symptoms. In comparison, rs445114 on chromosome 8q24 was marginally associated with decreased urinary symptoms (OR=0.83; 95% C.I. 0.66-1.01). CONCLUSIONS:: Using 38 SNPs that have been shown to predispose to PCa, we identified 3 SNPs that are additionally associated with a well-characterized LUTS phenotype. These SNPs may aid in the improved characterization of men with LUTS/BPH.