title: Association of prostate cancer risk variants with clinicopathologic characteristics of the disease.
abstract: OBJECTIVE
  Fifteen independent genetic variants have been implicated in prostate cancer risk by recent genome-wide association studies. However, their association with clinicopathologic features of prostate cancer is uncertain.
  
  
  METHODS
  We systematically evaluated these 15 variants in 1,563 prostate cancer patients undergoing radical prostatectomy, taking advantage of the uniform tumor stage and grade information available for each of these cases. Associations of these variants with aggressiveness, pathologic Gleason scores, pathologic stage, age at diagnosis, or serum prostate-specific antigen (PSA) levels were tested.
  
  
  RESULTS
  After adjusting for multiple testing, none of the single nucleotide polymorphisms was individually or cumulatively associated with aggressiveness or individual clinicopathologic variables of prostate cancer such as Gleason scores, pathologic stage, or age at diagnosis of prostate cancer. The reported risk allele (G) for single nucleotide polymorphism rs2735839 in the KLK3 gene at 19q13 was more frequent in less aggressive prostate cancer patients (0.89) than in more aggressive prostate cancer patients (0.86; nominal P = 0.03) or in controls (0.86; nominal P = 0.04). Considering that this allele was also significantly associated with higher serum PSA levels among controls (nominal P = 0.003), the observed trend of higher frequency of this risk allele between less and more aggressive prostate cancer, or between less aggressive and controls may be due to detection bias of PSA screening.
  
  
  CONCLUSIONS
  Prostate cancer risk variants recently discovered from genome-wide case-control association studies are not associated with clinicopathologic variables in this population. Case-case studies are urgently needed to discover genetic variants that predict tumor aggressiveness.
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Isaacs
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Wiley
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Fang-Chi
authors.initials: FC
authors.lastname: Hsu
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.forename: Aubrey R
authors.initials: AR
authors.lastname: Turner
authors.forename: Tamara S
authors.initials: TS
authors.lastname: Adams
authors.forename: Wennuan
authors.initials: W
authors.lastname: Liu
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Trock
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.forename: Baoli
authors.initials: B
authors.lastname: Chang
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Walsh
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: William
authors.initials: W
authors.lastname: Isaacs
authors.forename: Siqun
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):610-2
references.pmid: 17372260
references.citation: Nat Genet. 2007 May;39(5):638-44
references.pmid: 17401364
references.citation: Cancer Res. 2007 Apr 1;67(7):2951-6
references.pmid: 17409400
references.citation: Genome Res. 2007 Dec;17(12):1717-22
references.pmid: 17978284
references.citation: Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R103-21
references.pmid: 14749351
references.citation: Nat Genet. 2007 Aug;39(8):977-83
references.pmid: 17603485
references.citation: Nat Genet. 2008 Mar;40(3):281-3
references.pmid: 18264098
references.citation: Prostate. 2008 May 15;68(7):691-7
references.pmid: 18361410
references.citation: Urol Clin North Am. 2001 Aug;28(3):567-94
references.pmid: 11590815
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):809-14
references.pmid: 17416775
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14068-73
references.pmid: 16945910
references.citation: Am J Surg Pathol. 2005 Sep;29(9):1228-42
references.pmid: 16096414
references.citation: Nat Genet. 2006 Jun;38(6):652-8
references.pmid: 16682969
references.citation: Cancer Res. 2007 Apr 1;67(7):2944-50
references.pmid: 17409399
references.citation: Nat Genet. 2007 May;39(5):631-7
references.pmid: 17401366
references.citation: Nat Genet. 2008 Mar;40(3):310-5
references.pmid: 18264096
references.citation: J Natl Cancer Inst. 2007 Dec 19;99(24):1836-44
references.pmid: 18073375
references.citation: J Natl Cancer Inst. 2007 Oct 17;99(20):1525-33
references.pmid: 17925536
references.citation: N Engl J Med. 2008 Feb 28;358(9):910-9
references.pmid: 18199855
references.citation: Nat Genet. 2007 May;39(5):645-9
references.pmid: 17401363
references.citation: Eur J Hum Genet. 2008 Apr;16(4):496-505
references.pmid: 18231127
references.citation: Nat Genet. 2008 Mar;40(3):316-21
references.pmid: 18264097
references.citation: Microsc Res Tech. 2000 Dec 1;51(5):423-9
references.pmid: 11074612
references.citation: Nat Genet. 2007 Jul;39(7):906-13
references.pmid: 17572673
references.citation: Urology. 2008 Jul;72(1):172-6
references.pmid: 18304619