Gibbs M, Stanford J L, Jarvik G P, Janer M, Badzioch M, Peters M A, Goode E L, Kolb S, Chakrabarti L, Shook M, Basom R, Ostrander E A, Hood L
Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Am J Hum Genet. 2000 Jul;67(1):100-9. doi: 10.1086/302969. Epub 2000 May 19.
A 10-cM genomewide scan of 94 families with hereditary prostate cancer, including 432 affected men, was used to identify regions of putative prostate cancer-susceptibility loci. There was an average of 3.6 affected, genotyped men per family, and an overall mean age at diagnosis of 65.4 years. A total of 50 families were classified as early onset (mean age at diagnosis <66 years), and 44 families were classified as later onset (mean age at diagnosis > or =66 years). When the entire data set is considered, regions of interest (LOD score > or =1.5) were identified on chromosomes 10, 12, and 14, with a dominant model of inheritance. Under a recessive model LOD scores > or =1.5 were found on chromosomes 1, 8, 10, and 16. Stratification by age at diagnosis highlighted a putative susceptibility locus on chromosome 11, among the later-onset families, with a LOD score of 3. 02 (recombination fraction 0) at marker ATA34E08. Overall, this genomic scan suggests that there are multiple prostate cancer loci responsible for the hereditary form of this common and complex disease and that stratification by a variety of factors will be required for identification of all relevant genes.
对94个遗传性前列腺癌家族(包括432名患病男性)进行了全基因组扫描,扫描范围为10厘摩,以确定假定的前列腺癌易感基因座区域。每个家族平均有3.6名患病且进行了基因分型的男性,诊断时的总体平均年龄为65.4岁。共有50个家族被归类为早发型(诊断时平均年龄<66岁),44个家族被归类为晚发型(诊断时平均年龄≥66岁)。当考虑整个数据集时,在10号、12号和14号染色体上发现了感兴趣的区域(LOD评分≥1.5),遗传模式为显性。在隐性模式下,在1号、8号、10号和16号染色体上发现LOD评分≥1.5。按诊断年龄分层突出显示,在晚发型家族中,11号染色体上有一个假定的易感基因座,在标记ATA34E08处的LOD评分为3.02(重组率为0)。总体而言,这项基因组扫描表明,有多个前列腺癌基因座导致这种常见复杂疾病的遗传形式,并且需要通过多种因素进行分层才能识别所有相关基因。