V. Nwosu et al., Heterogeneity of genetic alterations in prostate cancer: evidence of the complex nature of the disease, HUM MOL GEN, 10(20), 2001, pp. 2313-2318
Prostate cancer is a complex, multifactorial disease with genetic and envir
onmental factors involved in its etiology. The search for genetic determina
nts involved in the disease has proven to be challenging, in part because s
uch complex diseases are often not amenable to characterization by linkage
analysis and positional cloning as is the case for diseases with simple Men
delian genetic inheritance. Prostate cancer susceptibility loci that have b
een reported so far include HPC1 (1q24-q25), PCAP (1q42-q43), HPCX (Xq27-q2
8), CAPB (1p36), HPC20 (20q13), HPC2/ELAC2 (17p11) and 16q23. Prostate canc
er aggressiveness loci have also been reported (5q31-q33, 7q32 and 19q12).
Further complicating the process is the existence of polymorphisms in sever
al genes associated with prostate cancer including, AR, PSA, SRD5A2, VDR an
d CYP isoforms. These polymorphisms, however, are not thought to be highly
penetrant alleles in families at high risk for prostate cancer. It is clear
that prostate cancer etiology involves several genetic loci with no major
gene accounting for a large proportion of susceptibility to the disease.