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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