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- ASO, allele specific oligonucleotide hybridisation
- BRCA1 and BRCA2, breast cancer predisposing genes
- HPC, hereditary prostate cancer
- PCR, polymerase chain reaction
- SIR, standardised incidence ratio
A fter lung cancer, prostate cancer is the second leading cause of death from cancer in men in developed countries.1 Despite the substantial impact on public health of prostate cancer, the cause of the disease has remained poorly understood, with ethnicity, diet, and family history considered as the major risk factors.2,3 A fraction of patients with prostate cancer belong to families with hereditary prostate cancer (HPC). Recently, several loci have been implicated in predisposing to prostate cancer by genetic linkage studies in cancer families, including HPC1 at 1q24–q25, HPC2 at 17p11, PCAP at 1q42.2–q43, HPCX at Xq27–q28, CAPB at 1p36, and HPC20 at 20q13.4 Only two genes have been identified from these chromosomal regions, ELAC2 (MIM 605367) from the HPC2, locus5 and RNASEL (MIM 180435) from the HPC1, locus6 but none has so far been definitively confirmed. In Finland, neither of these genes alone explains disease segregation in Finnish families with HPC but they seem to have some modifying role in predisposition to cancer.7,8
Breast cancer predisposing genes BRCA1 (MIM 113705) and BRCA2 (MIM 600185) are involved in repair of DNA damage and transcriptional regulation.9 Clustering of breast, ovarian, and prostate cancer has been reported,10–14 suggesting a role for BRCA1 and BRCA2 in predisposition to prostate cancer. Several epidemiological studies have discovered an increased risk of prostate cancer among BRCA1 and BRCA2 families.15–19 Consistent with this view, loss of heterozygosity at the BRCA1 and BRCA2 loci is commonly encountered in prostate cancer.20–22 Edwards et al23 implicated BRCA2 as a high risk gene for early onset prostate cancer. In a recent study in BRCA1 and BRCA2 mutation positive and mutation negative Finnish breast cancer families, the only increased standardised incidence ratio (SIR), besides breast and …