Individual and cumulative effect of prostate cancer risk-associated variants on clinicopathologic variables in 5,895 prostate cancer patients

A. Karim Kader, Jielin Sun, Sarah D. Isaacs, Kathleen E. Wiley, Guifang Yan, Seong Tae Kim, Helen Fedor, Angelo Michael Demarzo, Jonathan Ira Epstein, Patrick Walsh, Alan Wayne Partin, Bruce Trock, S. Lilly Zheng, Jianfeng Xu, William B Isaacs

Research output: Contribution to journalArticle

Abstract

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 ≥4+3, or stage ≥T3b, or N+) or less aggressive disease (Gleason scores ≤3+4, and stage ≤T2, and N0). For the two SNPs that had significant differences between more and less aggressive disease rs2735839 in KLK3 (P=8.4 × 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.

Original languageEnglish (US)
Pages (from-to)1195-1205
Number of pages11
JournalProstate
Volume69
Issue number11
DOIs
StatePublished - Aug 1 2009

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Prostatic Neoplasms
Single Nucleotide Polymorphism
Neoplasm Grading
Genome-Wide Association Study
Prostatectomy
Gene Frequency
Alleles
Neoplasms

Keywords

  • Aggressiveness
  • Association
  • Genetics
  • Gleason score
  • Prostate cancer
  • Stage

ASJC Scopus subject areas

  • Urology
  • Oncology
  • Medicine(all)

Cite this

Individual and cumulative effect of prostate cancer risk-associated variants on clinicopathologic variables in 5,895 prostate cancer patients. / Kader, A. Karim; Sun, Jielin; Isaacs, Sarah D.; Wiley, Kathleen E.; Yan, Guifang; Kim, Seong Tae; Fedor, Helen; Demarzo, Angelo Michael; Epstein, Jonathan Ira; Walsh, Patrick; Partin, Alan Wayne; Trock, Bruce; Zheng, S. Lilly; Xu, Jianfeng; Isaacs, William B.

In: Prostate, Vol. 69, No. 11, 01.08.2009, p. 1195-1205.

Research output: Contribution to journalArticle

Kader, A. Karim ; Sun, Jielin ; Isaacs, Sarah D. ; Wiley, Kathleen E. ; Yan, Guifang ; Kim, Seong Tae ; Fedor, Helen ; Demarzo, Angelo Michael ; Epstein, Jonathan Ira ; Walsh, Patrick ; Partin, Alan Wayne ; Trock, Bruce ; Zheng, S. Lilly ; Xu, Jianfeng ; Isaacs, William B. / Individual and cumulative effect of prostate cancer risk-associated variants on clinicopathologic variables in 5,895 prostate cancer patients. In: Prostate. 2009 ; Vol. 69, No. 11. pp. 1195-1205.
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abstract = "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 ≥4+3, or stage ≥T3b, or N+) or less aggressive disease (Gleason scores ≤3+4, and stage ≤T2, and N0). For the two SNPs that had significant differences between more and less aggressive disease rs2735839 in KLK3 (P=8.4 × 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.",
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T1 - Individual and cumulative effect of prostate cancer risk-associated variants on clinicopathologic variables in 5,895 prostate cancer patients

AU - Kader, A. Karim

AU - Sun, Jielin

AU - Isaacs, Sarah D.

AU - Wiley, Kathleen E.

AU - Yan, Guifang

AU - Kim, Seong Tae

AU - Fedor, Helen

AU - Demarzo, Angelo Michael

AU - Epstein, Jonathan Ira

AU - Walsh, Patrick

AU - Partin, Alan Wayne

AU - Trock, Bruce

AU - Zheng, S. Lilly

AU - Xu, Jianfeng

AU - Isaacs, William B

PY - 2009/8/1

Y1 - 2009/8/1

N2 - 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 ≥4+3, or stage ≥T3b, or N+) or less aggressive disease (Gleason scores ≤3+4, and stage ≤T2, and N0). For the two SNPs that had significant differences between more and less aggressive disease rs2735839 in KLK3 (P=8.4 × 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.

AB - 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 ≥4+3, or stage ≥T3b, or N+) or less aggressive disease (Gleason scores ≤3+4, and stage ≤T2, and N0). For the two SNPs that had significant differences between more and less aggressive disease rs2735839 in KLK3 (P=8.4 × 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.

KW - Aggressiveness

KW - Association

KW - Genetics

KW - Gleason score

KW - Prostate cancer

KW - Stage

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U2 - 10.1002/pros.20970

DO - 10.1002/pros.20970

M3 - Article

VL - 69

SP - 1195

EP - 1205

JO - Prostate

JF - Prostate

SN - 0270-4137

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