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  • Title: Genetic variants of the copy number polymorphic beta-defensin locus are associated with sporadic prostate cancer.
    Author: Huse 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.
    Journal: Tumour Biol; 2008; 29(2):83-92. PubMed ID: 18515986.
    Abstract:
    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 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. 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.
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