Document Detail

Individual and cumulative effect of prostate cancer risk-associated variants on clinicopathologic variables in 5,895 prostate cancer patients.
MedLine Citation:
PMID:  19434657     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: More than a dozen single nucleotide polymorphisms (SNPs) have been associated with prostate cancer (PCa) risk from genome-wide association studies (GWAS). Their association with PCa aggressiveness and clinicopathologic variables is inconclusive.
METHODS: Twenty PCa risk SNPs implicated in GWAS and fine mapping studies were evaluated in 5,895 PCa cases treated by radical prostatectomy at Johns Hopkins Hospital, where each tumor was uniformly graded and staged using the same protocol.
RESULTS: For 18 of the 20 SNPs examined, no statistically significant differences (P > 0.05) were observed in risk allele frequencies between patients with more aggressive (Gleason scores > or =4 + 3, or stage > or =T3b, or N+) or less aggressive disease (Gleason scores < or =3 + 4, and stage < or =T2, and N0). For the two SNPs that had significant differences between more and less aggressive disease rs2735839 in KLK3 (P = 8.4 x 10(-7)) and rs10993994 in MSMB (P = 0.046), the alleles that are associated with increased risk for PCa were more frequent in patients with less aggressive disease. Since these SNPs are known to be associated with PSA levels in men without PCa diagnoses, these latter associations may reflect the enrichment of low grade, low stage cases diagnosed by contemporary disease screening with PSA.
CONCLUSIONS: The vast majority of PCa risk-associated SNPs are not associated with aggressiveness and clinicopathologic variables of PCa. Correspondingly, they have minimal utility in predicting the risk for developing more or less aggressive forms of PCa.
A Karim Kader; Jielin Sun; Sarah D Isaacs; Kathleen E Wiley; Guifang Yan; Seong-Tae Kim; Helen Fedor; Angelo M DeMarzo; Jonathan I Epstein; Patrick C Walsh; Alan W Partin; Bruce Trock; S Lilly Zheng; Jianfeng Xu; William Isaacs
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Prostate     Volume:  69     ISSN:  1097-0045     ISO Abbreviation:  Prostate     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-06-29     Completed Date:  2009-07-20     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  8101368     Medline TA:  Prostate     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1195-205     Citation Subset:  IM    
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MeSH Terms
Cohort Studies
Gene Frequency
Genetic Predisposition to Disease / genetics*
Middle Aged
Polymorphism, Single Nucleotide / genetics*
Predictive Value of Tests
Prostate-Specific Antigen / blood,  genetics
Prostatic Neoplasms / blood,  genetics*,  surgery
Prostatic Secretory Proteins / genetics*
Retrospective Studies
Risk Factors
Tumor Markers, Biological / blood,  genetics
Grant Support
CA105055/CA/NCI NIH HHS; CA106523/CA/NCI NIH HHS; CA112517/CA/NCI NIH HHS; CA129684/CA/NCI NIH HHS; CA58236/CA/NCI NIH HHS; CA95052/CA/NCI NIH HHS; P50 CA058236/CA/NCI NIH HHS; P50 CA058236-09A10002/CA/NCI NIH HHS; R01 CA095052/CA/NCI NIH HHS; R01 CA095052-05/CA/NCI NIH HHS; R01 CA105055/CA/NCI NIH HHS; R01 CA105055-05/CA/NCI NIH HHS; R01 CA106523/CA/NCI NIH HHS; R01 CA106523-05/CA/NCI NIH HHS; R01 CA112517/CA/NCI NIH HHS; R01 CA112517-05/CA/NCI NIH HHS; R01 CA129684/CA/NCI NIH HHS; R01 CA129684-02/CA/NCI NIH HHS
Reg. No./Substance:
0/Prostatic Secretory Proteins; 0/Tumor Markers, Biological; 0/beta-microseminoprotein; EC Antigen

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