Genetic variants of the copy number polymorphic beta-defensin locus are associated with sporadic prostate cancer.

Authors:
Klaus Huse, Stefan Taudien, Marco Groth, Philip Rosenstiel, Karol Szafranski, Michael Hiller, Jochen Hampe, Kerstin Junker, Jorg Schubert, Stefan Schreiber, Gerd Birkenmeier, Michael Krawczak, Matthias Platzer
Year of publication:
2008
Volume:
29
Issue:
2
Issn:
1010-4283
Journal title abbreviated:
TUMOR BIOL
Journal title long:
Tumor biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (ISOBM)
Impact factor:
2.926
Abstract:
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 beta-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.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.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.Our findings imply a role of the antibacterial defensins in prostate cancerogenesis qualifying distinct gene variants and copy numbers as potential tumor markers.