PT  - JOURNAL ARTICLE
AU  - Gallagher, David J.
AU  - Vijai, Joseph
AU  - Cronin, Angel M.
AU  - Bhatia, Jasmine
AU  - Vickers, Andrew J.
AU  - Gaudet, Mia M.
AU  - Fine, Samson
AU  - Reuter, Victor
AU  - Scher, Howard I.
AU  - Halldén, Christer
AU  - Dutra-Clarke, Ana
AU  - Klein, Robert J.
AU  - Scardino, Peter T.
AU  - Eastham, James A.
AU  - Lilja, Hans
AU  - Kirchhoff, Tomas
AU  - Offit, Kenneth
TI  - Susceptibility Loci Associated with Prostate Cancer Progression and Mortality
AID  - 10.1158/1078-0432.CCR-10-0028
DP  - 2010 May 15
TA  - Clinical Cancer Research
PG  - 2819--2832
VI  - 16
IP  - 10
4099  - http://clincancerres.aacrjournals.org/content/16/10/2819.short
4100  - http://clincancerres.aacrjournals.org/content/16/10/2819.full
SO  - Clin Cancer Res2010 May 15; 16
AB  - 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. Clin Cancer Res; 16(10); 2819–32. ©2010 AACR.