Selected aspects of inherited susceptibility to prostate cancer and tumours of different site of origin

Research conducted over the last two decades has led us to believe that inherited factors play an important role in the aetiology of cancer [1-8]. Prostate cancer is among the leading causes of morbidity and mortality in men. Relatively little is known about the genetic determinants of this disease, but epidemiologic data suggest that dominant susceptibility genes may be responsible for up to 5% of all of cases [9,10]. Through linkage analysis, numerous chromosomal loci have been identified, but no clear prostate susceptibility gene has emerged. Three candidate susceptibility genes have been positionally cloned – HPC1, HPC2/ELAC2 and MSR1 – but a clear role for any of these genes in hereditary prostate cancer has not been established [11,12]. There is evidence that rare mutations of genes in the DNA damage signalling pathway and cell cycle control pathway (BRCA2, CHEK2 and NBS1) predispose to prostate cancer, but the contribution of these two genes to prostate cancer aetiology is relatively small [13]. Common variants in the genes in these pathways (CDKN1B, CDKN1A, ATMATM, XRCC1, ERCC2) also have been associated with an increased risk of prostate cancer [14-16]. The DNA damage signalling and cell cycle control pathways play a crucial role in the maintenance of the integrity of the genome in response to DNA damage and has been implicated in the pathogenesis of prostate cancer and of cancers at other sites. This paper reviews a range of studies which have been performed in Polish population with the following objectives:1) to investigate the association between inherited variation in RNASEL, MSR1, NBS1 and BRCA1 genes and prostate cancer risk in the Polish population;2) to investigate the role of CHEK2 mutations in inherited susceptibility to prostate cancer and malignancies of other sites in the Polish population.(based on: Cybulski C, Woko？orczyk D, Jakubowska A, Gliniewicz B, Sikorski A, Huzarski T, Debniak T, Narod SA, Lubiński J. DNA variation in MSR1, RNASEL and