Schaid Daniel J
Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R103-21. doi: 10.1093/hmg/ddh072. Epub 2004 Jan 28.
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 probably 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.
在大多数发达国家，前列腺癌是男性中最常见的癌症，但对其病因却知之甚少。老年、非洲裔血统以及前列腺癌家族史阳性长期以来一直被认为是重要的风险因素。遗传学可能起关键作用的证据基于多种研究设计，包括病例对照研究、队列研究、双胞胎研究和基于家族的研究，所有这些都将详细回顾。通过连锁研究寻找前列腺癌易感基因，早期曾寄希望于找到这些基因会像找到乳腺癌和结肠癌易感基因一样“容易”。然而，由于难以复制有希望的连锁区域，这种希望破灭了。本综述提供了近期进展的最新情况，以及对不同连锁研究中不同结果的广泛看法。早期的连锁研究结果为前列腺癌易感基因座提供了有针对性的候选区域，包括1号染色体1q23 - 25上的HPC1、1号染色体1q42 - 43上的PCAP、1号染色体1p36上的CAPB、与8号染色体8p22 - 23的连锁、17号染色体17p上的HPC2、20号染色体20q13上的HPC20以及X号染色体Xq27 - 28上的HPCX。这些连锁研究结果促使对几个强有力的候选基因进行精细定位和突变筛查，包括ELAC2、RNASEL和MSR1。到目前为止，总共完成了10项针对前列腺癌易感性的全基因组连锁扫描，并进行了综述。此外，还综述了近期关于 Gleason分级（一种衡量前列腺癌侵袭性的指标）与几个基因组区域相关的研究结果。最后，在寻找影响前列腺癌风险基因的背景下，简要讨论了环境和饮食风险因素以及可能在常见前列腺癌形式中起作用基因的常见基因多态性的作用。
