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Susceptibility Loci Associated with Prostate Cancer Progression and Mortality

Gallagher, David J. (författare)
Vijai, Joseph (författare)
Cronin, Angel M. (författare)
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Bhatia, Jasmine (författare)
Vickers, Andrew J. (författare)
Gaudet, Mia M. (författare)
Fine, Samson (författare)
Reuter, Victor (författare)
Scher, Howard I. (författare)
Halldén, Christer, 1957- (författare)
Memorial Sloan-Kettering Cancer Center, Biomedicin
Dutra-Clarke, Ana (författare)
Klein, Robert J. (författare)
Scardino, Peter T. (författare)
Eastham, James A. (författare)
Lilja, Hans (författare)
Kirchhoff, Tomas (författare)
Offit, Kenneth (författare)
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Lunds universitet Klinisk kemi, Malmö. (creator_code:org_t)
Lunds universitet EpiHealth: Epidemiology for Health. (creator_code:org_t)
Ingår i: Clinical Cancer Research. - American Association for Cancer Research. - 1078-0432. ; 16:10, s. 2819-2832
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
  • 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. (C) 2010 AACR.


MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)



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