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PURPOSE: Prostate cancer is a heterogeneous 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 publication

DOI

10.1158/1078-0432.CCR-10-0028

Type

Journal article

Journal

Clin Cancer Res

Publication Date

15/05/2010

Volume

16

Pages

2819 - 2832

Keywords

Aged, Disease Progression, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Polymorphism, Single Nucleotide, Prognosis, Proportional Hazards Models, Prostatic Neoplasms