title: Prostate cancer risk alleles are associated with prostate cancer volume and prostate size.
abstract: OBJECTIVE
  Genome-wide association studies have identified an increasing number of single nucleotide polymorphisms associated with prostate cancer risk. Some of these genetic variants are also associated with serum prostate specific antigen levels and lower urinary tract symptoms, raising the question of whether they are truly prostate cancer biomarkers or simply lead to detection bias. Therefore, we determined whether single nucleotide polymorphisms associated with prostate cancer risk are more strongly associated with tumor or prostate volume.
  
  
  METHODS
  The genotypes of 38 validated prostate cancer risk single nucleotide polymorphisms were determined in 1,321 white men who underwent radical prostatectomy. Univariate and multivariate analyses were performed to compare the relationship of single nucleotide polymorphism frequency with total prostate and tumor volumes.
  
  
  RESULTS
  On multivariate analysis 2 single nucleotide polymorphisms on chromosome 8q24, rs16901979 (A) and rs6983267 (G), were significantly associated with increased tumor volume (p=0.01 and 0.02, respectively). In contrast, rs17632542 (T) near the PSA gene on 19q13 was associated with significantly lower tumor volume and rs10788160 (A) on 10q26 was associated with significantly larger prostate volume (p=0.02 and 0.01, respectively).
  
  
  CONCLUSIONS
  Analysis of 38 single nucleotide polymorphisms associated with prostate cancer risk revealed a significant association between several on chromosome 8q24 and increased tumor volume but not prostate volume. This suggests that they are bona fide markers of prostate cancer susceptibility and possibly more aggressive disease. Other prostate cancer risk alleles are associated with prostate specific antigen and increased prostate or decreased tumor volume, suggesting detection bias due to their phenotypic influence.
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Daniel
authors.initials: D
authors.lastname: Reinhardt
authors.affiliation: Division of Urology, NorthShore University Healthcare System, Evanston, Illinois.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Helfand
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Cooper
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Roehl
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: William J
authors.initials: WJ
authors.lastname: Catalona
authors.affiliation: Department of Urology and Population Health, New York University and Manhattan Veterans Affairs, New York, New York. Electronic address: stacyloeb@gmail.com.
authors.forename: Stacy
authors.initials: S
authors.lastname: Loeb
mesh_terms: D000483:Alleles; D001706:Biopsy; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009929:Organ Size; D011110:Polymorphism, Genetic; D011467:Prostate / Q000473:pathology*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D012189:Retrospective Studies
chemical_list: D004273:DNA, Neoplasm
keywords: organ size; polymorphism; prostate; prostatic neoplasms; risk; single nucleotide