Genetic Variants of the Copy Number Polymorphic β-Defensin Locus Are Associated with Sporadic Prostate CancerHuse K. · Taudien S. · Groth M. · Rosenstiel P. · Szafranski K. · Hiller M. · Hampe J. · Junker K. · Schubert J. · Schreiber S. · Birkenmeier G. · Krawczak M. · Platzer M.
aGenome Analysis, Leibniz Institute for Age Research, Fritz Lipmann Institute and bDepartment of Urology, Friedrich Schiller University, Jena, cInstitute of Biochemistry, University of Leipzig, Leipzig, dInstitute for Clinical Molecular Biology and eInstitute of Medical Informatics and Statistics, Christian Albrechts University, Kiel, and fInstitute of Computer Science, Bioinformatics Group, Albert Ludwigs University Freiburg, Freiburg, Germany
Background/Aims: Prostate cancer represents the cancer with the highest worldwide prevalence in men. Chromosome 8p23 has shown suggestive genetic linkage to early-onset familial prostate cancer and is frequently deleted in cancer cells of the urogenital tract. Within this locus some β-defensin genes (among them DEFB4, DEFB103, DEFB104) are localized, which are arranged in a gene cluster shown to exhibit an extensive copy number variation in the population. This structural variation considerably hampers genetic studies. In a new approach considering both sequence as well as copy number variations we aimed to compare the defensin locus at 8p23 in prostate cancer patients and controls. Methods: We apply PCR/cloning-based haplotyping and high-throughput copy number determination methods which allow assessment of both individual haplotypes and gene copy numbers not accessible to conventional SNP-based genotyping. Results: We demonstrate association of four common DEFB104 haplotypes with the risk of prostate cancer in two independent patient cohorts. Moreover, we show that high copy numbers (>9) of the defensin gene cluster are significantly underrepresented in both patient samples. Conclusions: Our findings imply a role of the antibacterial defensins in prostate cancerogenesis qualifying distinct gene variants and copy numbers as potential tumor markers.
Genome Analysis, Leibniz Institute for Age Research, Fritz Lipmann Institute
DE–07745 Jena (Germany)
Tel. +49 3641 656 241, Fax +49 3641 656 255, E-Mail firstname.lastname@example.org
Received: October 30, 2007
Accepted: April 2, 2008
Published online: June 2, 2008
Number of Print Pages : 10
Number of Figures : 3, Number of Tables : 2, Number of References : 44
Tumor Biology (Tumor Markers, Tumor Targeting and Translational Cancer Research)
Vol. 29, No. 2, Year 2008 (Cover Date: July 2008)
Journal Editor: Stigbrand T. (Umeå), Rye P.D. (Oslo)
ISSN: 1010–4283 (Print), eISSN: 1423–0380 (Online)
For additional information: http://www.karger.com/TBI