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Blood Biomarker Levels to Aid Discovery of Cancer-Related Single-Nucleotide Polymorphisms: Kallikreins and Prostate Cancer.

Klein, Robert J; Halldén, Christer LU ; Cronin, Angel M; Ploner, Alexander; Wiklund, Fredrik; Bjartell, Anders LU ; Stattin, Pär; Xu, Jianfeng; Scardino, Peter T and Offit, Kenneth, et al. (2010) In Cancer Prevention Research May 4. p.611-619
Abstract
Polymorphisms associated with prostate cancer include those in three genes encoding major secretory products of the prostate: KLK2 (encoding kallikrein-related peptidase 2; hK2), KLK3 (encoding prostate-specific antigen; PSA), and MSMB (encoding beta-microseminoprotein). PSA and hK2, members of the kallikrein family, are elevated in sera of men with prostate cancer. In a comprehensive analysis that included sequencing of all coding, flanking, and 2 kb of putative promoter regions of all 15 kallikrein (KLK) genes spanning approximately 280 kb on chromosome 19q, we identified novel single-nucleotide polymorphisms (SNP) and genotyped 104 SNPs in 1,419 cancer cases and 736 controls in Cancer Prostate in Sweden 1, with independent replication... (More)
Polymorphisms associated with prostate cancer include those in three genes encoding major secretory products of the prostate: KLK2 (encoding kallikrein-related peptidase 2; hK2), KLK3 (encoding prostate-specific antigen; PSA), and MSMB (encoding beta-microseminoprotein). PSA and hK2, members of the kallikrein family, are elevated in sera of men with prostate cancer. In a comprehensive analysis that included sequencing of all coding, flanking, and 2 kb of putative promoter regions of all 15 kallikrein (KLK) genes spanning approximately 280 kb on chromosome 19q, we identified novel single-nucleotide polymorphisms (SNP) and genotyped 104 SNPs in 1,419 cancer cases and 736 controls in Cancer Prostate in Sweden 1, with independent replication in 1,267 cases and 901 controls in Cancer Prostate in Sweden 2. This verified prior associations of SNPs in KLK2 and in MSMB (but not in KLK3) with prostate cancer. Twelve SNPs in KLK2 and KLK3 were associated with levels of PSA forms or hK2 in plasma of control subjects. Based on our comprehensive approach, this is likely to represent all common KLK variants associated with these phenotypes. A T allele at rs198977 in KLK2 was associated with increased cancer risk and a striking decrease of hK2 levels in blood. We also found a strong interaction between rs198977 genotype and hK2 levels in blood in predicting cancer risk. Based on this strong association, we developed a model for predicting prostate cancer risk from standard biomarkers, rs198977 genotype, and rs198977 x hK2 interaction; this model had greater accuracy than did biomarkers alone (area under the receiver operating characteristic curve, 0.874 versus 0.866), providing proof in principle to clinical application for our findings. Cancer Prev Res; 3(5); 611-9. (c)2010 AACR. (Less)
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Cancer Prevention Research
volume
May 4
pages
611 - 619
publisher
American Association for Cancer Research
external identifiers
  • wos:000277294000007
  • pmid:20424135
  • scopus:77952026425
ISSN
1940-6207
DOI
10.1158/1940-6207.CAPR-09-0206
language
English
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yes
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7c1c148a-fbaa-428a-9e64-9b0164200605 (old id 1594728)
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http://www.ncbi.nlm.nih.gov/pubmed/20424135?dopt=Abstract
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2010-05-04 23:07:52
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2018-06-03 04:29:45
@article{7c1c148a-fbaa-428a-9e64-9b0164200605,
  abstract     = {Polymorphisms associated with prostate cancer include those in three genes encoding major secretory products of the prostate: KLK2 (encoding kallikrein-related peptidase 2; hK2), KLK3 (encoding prostate-specific antigen; PSA), and MSMB (encoding beta-microseminoprotein). PSA and hK2, members of the kallikrein family, are elevated in sera of men with prostate cancer. In a comprehensive analysis that included sequencing of all coding, flanking, and 2 kb of putative promoter regions of all 15 kallikrein (KLK) genes spanning approximately 280 kb on chromosome 19q, we identified novel single-nucleotide polymorphisms (SNP) and genotyped 104 SNPs in 1,419 cancer cases and 736 controls in Cancer Prostate in Sweden 1, with independent replication in 1,267 cases and 901 controls in Cancer Prostate in Sweden 2. This verified prior associations of SNPs in KLK2 and in MSMB (but not in KLK3) with prostate cancer. Twelve SNPs in KLK2 and KLK3 were associated with levels of PSA forms or hK2 in plasma of control subjects. Based on our comprehensive approach, this is likely to represent all common KLK variants associated with these phenotypes. A T allele at rs198977 in KLK2 was associated with increased cancer risk and a striking decrease of hK2 levels in blood. We also found a strong interaction between rs198977 genotype and hK2 levels in blood in predicting cancer risk. Based on this strong association, we developed a model for predicting prostate cancer risk from standard biomarkers, rs198977 genotype, and rs198977 x hK2 interaction; this model had greater accuracy than did biomarkers alone (area under the receiver operating characteristic curve, 0.874 versus 0.866), providing proof in principle to clinical application for our findings. Cancer Prev Res; 3(5); 611-9. (c)2010 AACR.},
  author       = {Klein, Robert J and Halldén, Christer and Cronin, Angel M and Ploner, Alexander and Wiklund, Fredrik and Bjartell, Anders and Stattin, Pär and Xu, Jianfeng and Scardino, Peter T and Offit, Kenneth and Vickers, Andrew J and Grönberg, Henrik and Lilja, Hans},
  issn         = {1940-6207},
  language     = {eng},
  pages        = {611--619},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Prevention Research},
  title        = {Blood Biomarker Levels to Aid Discovery of Cancer-Related Single-Nucleotide Polymorphisms: Kallikreins and Prostate Cancer.},
  url          = {http://dx.doi.org/10.1158/1940-6207.CAPR-09-0206},
  volume       = {May 4},
  year         = {2010},
}