Susceptibility loci associated with prostate cancer progression and mortality

David J. Gallagher, Joseph Vijai, Angel M. Cronin, Jasmine Bhatia, Andrew J. Vickers, Mia M. Gaudet, Samson Fine, Victor Reuter, Howard I. Scher, Christer Halldén, Ana Dutra-Clarke, Robert J. Klein, Peter T. Scardino, James A. Eastham, Hans Lilja, Tomas Kirchhoff, Kenneth Offit

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


Purpose: Prostate cancer is a heterogenous disease with a variable natural history that is not accurately predicted by currently used prognostic tools. Experimental Design: We genotyped 798 prostate cancer cases of Ashkenazi Jewish ancestry treated for localized prostate cancer between June 1988 and December 2007. Blood samples were prospectively collected and de-identified before being genotyped and matched to clinical data. The survival analysis was adjusted for Gleason score and prostate-specific antigen. We investigated associations between 29 single nucleotide polymorphisms (SNP) and biochemical recurrence, castration-resistant metastasis, and prostate cancer-specific survival. Subsequently, we did an independent analysis using a high-resolution panel of 13 SNPs. Results: On univariate analysis, two SNPs were associated (P < 0.05) with biochemical recurrence, three SNPs were associated with clinical metastases, and one SNP was associated with prostate cancer-specific mortality. Applying a Bonferroni correction (P < 0.0017), one association with biochemical recurrence (P = 0.0007) was significant. Three SNPs showed associations on multivariable analysis, although not after correcting for multiple testing. The secondary analysis identified an additional association with prostate cancer-specific mortality in KLK3 (P < 0.0005 by both univariate and multivariable analysis). Conclusions: We identified associations between prostate cancer susceptibility SNPs and clinical end points. The rs61752561 in KLK3 and rs2735839 in the KLK2-KLK3 intergenic region were strongly associated with prostate cancer-specific survival, and rs10486567 in the 7JAZF1 gene were associated with biochemical recurrence. A larger study will be required to independently validate these findings and determine the role of these SNPs in prognostic models.

Original languageEnglish
Pages (from-to)2819-2832
Number of pages14
JournalClinical Cancer Research
Issue number10
StatePublished - 15 May 2010
Externally publishedYes


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