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Evaluation of Multiple Risk-Associated Single Nucleotide Polymorphisms Versus Prostate-Specific Antigen at Baseline to Predict Prostate Cancer in Unscreened Men

Klein, Robert J.; Halldén, Christer LU ; Gupta, Amit; Savage, Caroline J.; Dahlin, Anders LU ; Bjartell, Anders LU ; Manjer, Jonas LU ; Scardino, Peter T.; Ulmert, David LU and Wallström, Peter LU , et al. (2012) In European Urology 61(3). p.471-477
Abstract
Background: Although case-control studies have identified numerous single nucleotide polymorphisms (SNPs) associated with prostate cancer, the clinical role of these SNPs remains unclear. Objective: Evaluate previously identified SNPs for association with prostate cancer and accuracy in predicting prostate cancer in a large prospective population-based cohort of unscreened men. Design, setting, and participants: This study used a nested case-control design based on the Malmo Diet and Cancer cohort with 943 men diagnosed with prostate cancer and 2829 matched controls. Blood samples were collected between 1991 and 1996, and follow-up lasted through 2005. Measurements: We genotyped 50 SNPs, analyzed prostate-specific antigen (PSA) in blood... (More)
Background: Although case-control studies have identified numerous single nucleotide polymorphisms (SNPs) associated with prostate cancer, the clinical role of these SNPs remains unclear. Objective: Evaluate previously identified SNPs for association with prostate cancer and accuracy in predicting prostate cancer in a large prospective population-based cohort of unscreened men. Design, setting, and participants: This study used a nested case-control design based on the Malmo Diet and Cancer cohort with 943 men diagnosed with prostate cancer and 2829 matched controls. Blood samples were collected between 1991 and 1996, and follow-up lasted through 2005. Measurements: We genotyped 50 SNPs, analyzed prostate-specific antigen (PSA) in blood from baseline, and tested for association with prostate cancer using the Cochran-Mantel-Haenszel test. We further developed a predictive model using SNPs nominally significant in univariate analysis and determined its accuracy to predict prostate cancer. Results and limitations: Eighteen SNPs at 10 independent loci were associated with prostate cancer. Four independent SNPs at four independent loci remained significant after multiple test correction (p < 0.001). Seven SNPs at five independent loci were associated with advanced prostate cancer defined as clinical stage >= T3 or evidence of metastasis at diagnosis. Four independent SNPs were associated with advanced or aggressive cancer defined as stage >= T3, metastasis, Gleason score >= 8, or World Health Organization grade 3 at diagnosis. Prostate cancer risk prediction with SNPs alone was less accurate than with PSA at baseline (area under the curve of 0.57 vs 0.79), with no benefit from combining SNPs with PSA. This study is limited by our reliance on clinical diagnosis of prostate cancer; there are likely undiagnosed cases among our control group. Conclusions: Only a few previously reported SNPs were associated with prostate cancer risk in the large prospective Diet and Cancer cohort in Malmo, Sweden. SNPs were less useful in predicting prostate cancer risk than PSA at baseline. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. (Less)
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keywords
Prostate cancer, Biomarkers, SNPs, PSA, Sensitivity and specificity
in
European Urology
volume
61
issue
3
pages
471 - 477
publisher
Elsevier
external identifiers
  • wos:000300194000018
  • scopus:84856380174
ISSN
1873-7560
DOI
10.1016/j.eururo.2011.10.047
language
English
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yes
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24d00963-a1f8-4eee-bfd8-1be31f14b38a (old id 2403354)
date added to LUP
2012-04-02 09:29:02
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2017-09-10 04:22:03
@article{24d00963-a1f8-4eee-bfd8-1be31f14b38a,
  abstract     = {Background: Although case-control studies have identified numerous single nucleotide polymorphisms (SNPs) associated with prostate cancer, the clinical role of these SNPs remains unclear. Objective: Evaluate previously identified SNPs for association with prostate cancer and accuracy in predicting prostate cancer in a large prospective population-based cohort of unscreened men. Design, setting, and participants: This study used a nested case-control design based on the Malmo Diet and Cancer cohort with 943 men diagnosed with prostate cancer and 2829 matched controls. Blood samples were collected between 1991 and 1996, and follow-up lasted through 2005. Measurements: We genotyped 50 SNPs, analyzed prostate-specific antigen (PSA) in blood from baseline, and tested for association with prostate cancer using the Cochran-Mantel-Haenszel test. We further developed a predictive model using SNPs nominally significant in univariate analysis and determined its accuracy to predict prostate cancer. Results and limitations: Eighteen SNPs at 10 independent loci were associated with prostate cancer. Four independent SNPs at four independent loci remained significant after multiple test correction (p &lt; 0.001). Seven SNPs at five independent loci were associated with advanced prostate cancer defined as clinical stage &gt;= T3 or evidence of metastasis at diagnosis. Four independent SNPs were associated with advanced or aggressive cancer defined as stage &gt;= T3, metastasis, Gleason score &gt;= 8, or World Health Organization grade 3 at diagnosis. Prostate cancer risk prediction with SNPs alone was less accurate than with PSA at baseline (area under the curve of 0.57 vs 0.79), with no benefit from combining SNPs with PSA. This study is limited by our reliance on clinical diagnosis of prostate cancer; there are likely undiagnosed cases among our control group. Conclusions: Only a few previously reported SNPs were associated with prostate cancer risk in the large prospective Diet and Cancer cohort in Malmo, Sweden. SNPs were less useful in predicting prostate cancer risk than PSA at baseline. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.},
  author       = {Klein, Robert J. and Halldén, Christer and Gupta, Amit and Savage, Caroline J. and Dahlin, Anders and Bjartell, Anders and Manjer, Jonas and Scardino, Peter T. and Ulmert, David and Wallström, Peter and Vickers, Andrew J. and Lilja, Hans},
  issn         = {1873-7560},
  keyword      = {Prostate cancer,Biomarkers,SNPs,PSA,Sensitivity and specificity},
  language     = {eng},
  number       = {3},
  pages        = {471--477},
  publisher    = {Elsevier},
  series       = {European Urology},
  title        = {Evaluation of Multiple Risk-Associated Single Nucleotide Polymorphisms Versus Prostate-Specific Antigen at Baseline to Predict Prostate Cancer in Unscreened Men},
  url          = {http://dx.doi.org/10.1016/j.eururo.2011.10.047},
  volume       = {61},
  year         = {2012},
}