title: Genetic sequence variants are associated with severity of lower urinary tract symptoms and prostate cancer susceptibility.
abstract: OBJECTIVE
  While a clear heritable component underlies lower urinary tract symptoms and benign prostatic hyperplasia, few studies have identified specific genetic factors. In contrast, recent genome-wide association studies identified single nucleotide polymorphisms that increase prostate cancer risk. Some of these single nucleotide polymorphisms may also predispose to surgical intervention for benign prostatic hyperplasia. We determined whether these single nucleotide polymorphisms are also associated with lower urinary tract symptom severity and benign prostatic hyperplasia medication use.
  
  
  METHODS
  The genotypes of 38 single nucleotide polymorphisms previously associated with prostate cancer risk were determined for 1,168 healthy white male volunteers. American Urological Association symptom index score and medication for benign prostatic hyperplasia were documented prospectively. Statistical analyses were done to compare the frequency of the single nucleotide polymorphisms with American Urological Association symptom index and benign prostatic hyperplasia medication use.
  
  
  RESULTS
  Several single nucleotide polymorphisms, including rs2736098 on chromosome 5p15, showed a significant relationship with benign prostatic hyperplasia medication. After adjusting for the other genetic variants, patient age and medication use, rs1571801 on chromosome 9q33.2 (OR 1.31, 95% CI 1.0-1.74) and rs5945572 on chromosome Xp11 (OR 1.28, 95% CI 1.04-1.59) were significantly associated with increased urinary symptoms. In contrast, rs445114 on chromosome 8q24 was marginally associated with decreased urinary symptoms (OR 0.83, 95% CI 0.66-1.01).
  
  
  CONCLUSIONS
  Of 38 single nucleotide polymorphisms that predispose to prostate cancer we identified 3 that are also associated with a well characterized lower urinary tract symptom phenotype. These single nucleotide polymorphisms may aid in the improved characterization of men with lower urinary tract symptoms/benign prostatic hyperplasia.
authors.affiliation: Division of Urology, Department of Surgery, NorthShore University Health System, Evanston, Illinois, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Helfand
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Hu
authors.forename: Stacy
authors.initials: S
authors.lastname: Loeb
authors.forename: Kevin T
authors.initials: KT
authors.lastname: McVary
authors.forename: William J
authors.initials: WJ
authors.lastname: Catalona
mesh_terms: D004273:DNA, Neoplasm / Q000032:analysis*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D059411:Lower Urinary Tract Symptoms / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011471:Prostatic Neoplasms / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D014481:United States / Q000453:epidemiology; D014563:Urodynamics
chemical_list: D004273:DNA, Neoplasm