Clinical genetics of prostate cancer
Journal Title: Postępy Nauk Medycznych - Year 2010, Vol 23, Issue 11
Abstract
Epidemiologic research conducted over the last two decades has led us to believe that inherited factors play an important role in the etiology of prostate cancer, but the genes, which underlie the inherited susceptibility are elusive. Through linkage analysis, numerous prostate cancer susceptibility chromosomal loci have been identified including HPC1 (1q25-25), PCaP (1q42-43), HPCX (Xq27-28), CAPB (1p36), HPC2 (17p12), HPC20 (20q13) and 8p22-23. Three candidate susceptibility genes have been positionally cloned. HPC1, HPC2/ELAC2, and MSR1, but any of these is not a high-risk prostate cancer susceptibility gene. The most compelling associations for prostate cancer described to date are with genes involved in the DNA damage repair including, including BRCA2. In Poland, we have initiated a program to identify DNA variants, which confer an increased risk of prostate cancer. We found that germline mutations in BRCA1, CHEK2, NBS1confer an increased prostate cancer risk in Polish men. Our studies provide evidence that the list of known genetic markers of high risk of prostate cancer can be extended by specific mutations in NBS1, BRCA1 and CHEK2 genes in men with a positive family history of prostate cancer in at least one first or second degree relative (the risk increased about 5-15 fold). Identification of genetic markers of prostate cancer susceptibility will improve prevention, diagnosis and management with prostate cancer in Poland. In the past year, the results of several genome-wide searches for loci for cancer susceptibility prostate cancer have been reported. Several chromosomal regions of interest have been identified, including loci on chromosomes 2, 3, 6, 7, 8, 10, 11, 17, 19 and X. Identification of genetic markers of prostate cancer susceptibility will improve prevention, diagnosis and management with prostate cancer. These DNA variants may be included in the panel of markers designed to estimate the risk of prostate cancer in a given population.
Authors and Affiliations
Cezary Cybulski, Bartosz Gliniewicz, Adam Gołąb, Andrzej Sikorski, Jan Lubiński
Keywords
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