Susceptibility loci associated with prostate cancer progression and mortality Journal Article


Authors: Gallagher, D. J.; Vijai, J.; Cronin, A. M.; Bhatia, J.; Vickers, A. J.; Gaudet, M. M.; Fine, S.; Reuter, V.; Scher, H. I.; Halldén, C.; Dutra Clarke, A.; Klein, R. J.; Scardino, P. T.; Eastham, J. A.; Lilja, H.; Kirchhoff, T.; Offit, K.
Article Title: Susceptibility loci associated with prostate cancer progression and mortality
Abstract: 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. ©2010 AACR.
Keywords: adult; cancer survival; aged; middle aged; major clinical study; single nucleotide polymorphism; polymorphism, single nucleotide; cancer growth; neoplasm staging; prospective study; prostate specific antigen; cancer susceptibility; genetic predisposition to disease; neoplasm recurrence, local; proportional hazards models; gene locus; genotype; genome-wide association study; cancer mortality; prostate cancer; kaplan-meiers estimate; gleason score; prostatic neoplasms; oncogene; blood sampling; disease progression; genetic susceptibility; jew; 7jazf1 gene; klk3 gene
Journal Title: Clinical Cancer Research
Volume: 16
Issue: 10
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2010-05-15
Start Page: 2819
End Page: 2832
Language: English
DOI: 10.1158/1078-0432.ccr-10-0028
PUBMED: 20460480
PROVIDER: scopus
PMCID: PMC3732009
DOI/URL:
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: CCREF" - "Source: Scopus"
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MSK Authors
  1. Kenneth Offit
    509 Offit
  2. Peter T Scardino
    621 Scardino
  3. Hans Gosta Lilja
    286 Lilja
  4. Andrew J Vickers
    556 Vickers
  5. Angel M Cronin
    145 Cronin
  6. James Eastham
    426 Eastham
  7. Robert J. Klein
    59 Klein
  8. Vijai Joseph
    117 Joseph
  9. Samson W Fine
    315 Fine
  10. Victor Reuter
    901 Reuter
  11. Howard Scher
    818 Scher
  12. Jasmine Bhatia
    11 Bhatia