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

Abstract

Epidemiologic research conducted over the last two decades has led us to believe that inherited factors play an important role in the aetiology of prostate cancer, but the genes which underlie the inherited susceptibility are elusive. The most compelling associations to date are with genes involved in DNA damage repair, including BRCA2. In Poland we have initiated a programme to identify DNA variants which confer an increased risk of prostate cancer and other cancers. Here we review our recent results. We found that germline mutations in BRCA1, CHEK2 and NBS1 confer an increased prostate cancer risk in Polish men. We provide evidence that CHEK2 is a multi-organ cancer susceptibility gene. We show that inherited variation in RNASEL and MSR1 genes do not contribute to prostate cancer development in Poland.

Figure 1

Pedigrees of NBS1 mutation positive cases with familial prostate cancer.

Figure 2

Pedigrees of BRCA1 mutation positive cases with familial prostate cancer.

Figure 3

A 5395 bp deletion of exons 9 and 10 of CHEK2 detected in the Polish population: A – sequencing chromatogram of PCR product containing the deletion; B – location of deletion breakpoints on chromosome 22 in Alu-repeats (shown in bold).