Cunningham Julie M, McDonnell Shannon K, Marks Angela, Hebbring Scott, Anderson Sarah A, Peterson Brett J, Slager Susan, French Amy, Blute Michael L, Schaid Daniel J, Thibodeau Stephen N
Department of Laboratory Medicine and Pathology, Mayo Clinic/Foundation, Rochester, Minnesota 55905, USA.
Prostate. 2003 Dec 1;57(4):335-46. doi: 10.1002/pros.10308.
Prostate cancer is one of the most common cancers among men and has long been recognized to occur in familial clusters. Brothers and sons of affected men have a twofold to threefold increased risk of developing prostate cancer. However, identification of genetic susceptibility loci for prostate cancer has been extremely difficult. Several putative loci identified by genetic linkage have been reported to exist on chromosomes 1 (HPC1, PCAP, and CAPB), X (HPCX), 17 (HPC2), and 20 (HPC20), with genes RNASEL (HPC1) and ELAC2 (HPC2) tentatively defined. In this study, we report our genome linkage scan in 160 prostate cancer families, using the ABI Prism Linkage Mapping Set Version 2 with 402 microsatellite markers. The most significant linkage was found for chromosome 20, with a recessive model heterogeneity LOD score (HLOD) of 4.77, and a model-free LOD score (LOD - ZLR) of 3.46 for the entire group of pedigrees. Linkage for chromosome 20 was most prominent among families with a late age of diagnosis (average age at diagnosis >/= 66 years; maximum LOD - ZLR = 2.82), with <5 affected family members (LOD - ZLR = 3.02), with presence of hereditary prostate cancer (LOD - ZLR = 2.81), or with no male-to-male transmission of disease (LOD - ZLR = 3.84). No other chromosome showed significant evidence for linkage. However, chromosomes 6 and X showed suggestive results, with maximum LOD - ZLR values of 1.38 and 1.36, respectively. Subset analyses suggest additional chromosomal regions worth further follow-up.
前列腺癌是男性中最常见的癌症之一，长期以来人们一直认识到它会在家族中聚集发生。患病男性的兄弟和儿子患前列腺癌的风险会增加两到三倍。然而，确定前列腺癌的遗传易感性位点极其困难。据报道，通过基因连锁确定的几个假定位点存在于1号染色体（HPC1、PCAP和CAPB）、X染色体（HPCX）、17号染色体（HPC2）和20号染色体（HPC20）上，基因RNASEL（HPC1）和ELAC2（HPC2）被初步确定。在本研究中，我们报告了对160个前列腺癌家族进行的全基因组连锁扫描，使用了带有402个微卫星标记的ABI Prism连锁图谱集版本2。在20号染色体上发现了最显著的连锁，整个家系组的隐性模型异质性LOD分数（HLOD）为4.77，无模型LOD分数（LOD - ZLR）为3.46。20号染色体的连锁在诊断年龄较晚的家族中最为突出（诊断时的平均年龄≥66岁；最大LOD - ZLR = 2.82），患病家庭成员少于5人（LOD - ZLR = 3.02），存在遗传性前列腺癌（LOD - ZLR = 2.81），或不存在疾病的男性对男性传播（LOD - ZLR = 3.84）。没有其他染色体显示出显著的连锁证据。然而，6号和X号染色体显示出提示性结果，最大LOD - ZLR值分别为1.38和1.36。亚组分析表明还有其他染色体区域值得进一步随访。
