NDLI: Blood biomarker levels to aid discovery of cancer-related single-nucleotide polymorphisms: kallikreins and prostate cancer.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Klein, Robert J. Halldén, Christer Cronin, Angel M. Ploner, Alexander Wiklund, Fredrik Bjartell, Anders S. Stattin, Pär Xu, Jianfeng Scardino, Peter T. Offit, Kenneth Vickers, Andrew J. Grönberg, Henrik Lilja, Hans
Description	Country affiliation: United States Author Affiliation: Klein RJ ( Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.)
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.
File Format	HTM / HTML
ISSN	19406207
e-ISSN	19406215
DOI	10.1158/1940-6207.CAPR-09-0206
Journal	Cancer Prevention Research
Issue Number	5
Volume Number	3
Language	English
Publisher	American Association for Cancer Research
Publisher Date	2010-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Oncology Tumor Markers, Biological Genetic Predisposition To Disease Kallikreins Genetics Prostatic Neoplasms Area Under Curve Case-control Studies Genotype Polymerase Chain Reaction Polymorphism, Single Nucleotide Prostate-specific Antigen Blood Roc Curve Risk Factors Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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Blood biomarker levels to aid discovery of cancer-related single nucleotide polymorphisms: kallikreins and prostate cancer

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