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Susceptibility Loci...
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Gallagher, David J.
(author)
Susceptibility Loci Associated with Prostate Cancer Progression and Mortality
- Article/chapterEnglish2010
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LIBRIS-ID:oai:lup.lub.lu.se:a73045ed-0e50-437f-969a-5b2a38e5b1d3
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https://lup.lub.lu.se/record/1631469URI
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https://doi.org/10.1158/1078-0432.CCR-10-0028DOI
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Language:English
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Summary in:English
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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.
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Vijai, Joseph
(author)
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Cronin, Angel M.
(author)
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Bhatia, Jasmine
(author)
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Vickers, Andrew J.
(author)
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Gaudet, Mia M.
(author)
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Fine, Samson
(author)
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Reuter, Victor
(author)
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Scher, Howard I.
(author)
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Halldén, ChristerLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups(Swepub:lu)klke-cha
(author)
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Dutra-Clarke, Ana
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Klein, Robert J.
(author)
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Scardino, Peter T.
(author)
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Eastham, James A.
(author)
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Lilja, HansLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups(Swepub:lu)klke-hli
(author)
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Kirchhoff, Tomas
(author)
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Offit, Kenneth
(author)
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Klinisk kemi, MalmöForskargrupper vid Lunds universitet
(creator_code:org_t)
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In:Clinical Cancer Research16:10, s. 2819-28321078-0432
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Gallagher, David ...
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Vijai, Joseph
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Cronin, Angel M.
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Bhatia, Jasmine
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Vickers, Andrew ...
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Gaudet, Mia M.
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Fine, Samson
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Reuter, Victor
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Scher, Howard I.
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Halldén, Christe ...
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Dutra-Clarke, An ...
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Klein, Robert J.
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Scardino, Peter ...
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Eastham, James A ...
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Lilja, Hans
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Kirchhoff, Tomas
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Offit, Kenneth
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- MEDICAL AND HEALTH SCIENCES
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Clinical Cancer ...
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Lund University