Human Molecular Genetics Advance Access published online on January 28, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh072
© 2004 by Oxford University Press
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1 Department of Health Sciences Research, Harwick 775, Section of Biostatistics, Mayo Clinic College of Medicine, Rochester, MN 55905
* To whom correspondence should be addressed. E-mail: schaid{at}mayo.edu.
Prostate cancer is the most frequent cancer among men in most developed countries, yet little is known about its causes. Older age, African ancestry, and a positive family history of prostate cancer have long been recognized as important risk factors. The evidence that genetics likely plays a critical role is based on a variety of study designs, including case-control, cohort, twin, and family-based, all of which are reviewed in detail. The search for prostate cancer susceptibility genes by linkage studies offered early hope that finding genes would be as "easy" as finding genes for breast cancer and colon cancer susceptibilities. However, this hope has been dampened by the difficulty of replicating promising regions of linkage. This review provides updates on recent developments, and a broad view of the disparate findings from different linkage studies. Early linkage results have provided targeted candidate regions for prostate cancer susceptibility loci, including HPC1 on chromosome 1q23-25, PCAP on chromosome 1q42-43, CAPB on chromosome 1p36, linkage to chromosome 8p22-23, HPC2 on chromosome 17p, HPC20 on chromosome 20q13, and HPCX on chromosome Xq27-28. These linkage findings lead to refined mapping and mutation screening of several strong candidate genes, including ELAC2, RNASEL, and MSR1. Up to now, a total of 10 genome-wide linkage scans for prostate cancer susceptibility have been completed, and are reviewed. Furthermore, recent findings that Gleason's grade, a measure of aggressiveness of prostate cancer, is linked to several genomic regions are reviewed. Finally, the roles of environmental and dietary risk factors, and common genetic polymorphisms of genes likely to play a role in common forms of prostate cancer, are briefly discussed within in the context of searching for genes that influence prostate cancer risk. Key Words:
familial aggregation, segregation, linkage, twin studies, Gleason grade
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The Complex Genetic Epidemiology of Prostate Cancer
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