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Individual and cumulative effect of prostate cancer risk‐associated variants on clinicopathologic variables in 5,895 prostate cancer patients
Author(s) -
Kader A. Karim,
Sun Jielin,
Isaacs Sarah D.,
Wiley Kathleen E.,
Yan Guifang,
Kim SeongTae,
Fedor Helen,
DeMarzo Angelo M.,
Epstein Jonathan I.,
Walsh Patrick C.,
Partin Alan W.,
Trock Bruce,
Zheng S. Lilly,
Xu Jianfeng,
Isaacs William
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20970
Subject(s) - prostate cancer , single nucleotide polymorphism , medicine , prostatectomy , oncology , prostate , genome wide association study , cancer , genotype , biology , genetics , gene
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. Prostate 69:1195–1205, 2009. © 2009 Wiley‐Liss, Inc.