Schleutker J, Matikainen M, Smith J, Koivisto P, Baffoe-Bonnie A, Kainu T, Gillanders E, Sankila R, Pukkala E, Carpten J, Stephan D, Tammela T, Brownstein M, Bailey-Wilson J, Trent J, Kallioniemi O P
Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA.
Clin Cancer Res. 2000 Dec;6(12):4810-5.
Several predisposition loci for hereditary prostate cancer (HPC) have been suggested, including HPC1 at 1q24-q25 (OMIM #601518) and HPCX at Xq27-q28 (OMIM #300147). Genetically homogeneous populations, such as that of Finland, and distinct subsets of families may help to minimize the genetic heterogeneity that complicates the genetic dissection of complex traits. Here, the role of the HPC1, and HPCX loci in a series of Finnish prostate cancer families was studied, especially in subgroups of families defined by age, number of affected cases, and the mode of disease transmission. DNA samples were collected from 57 Finnish HPC families with at least two living prostate cancer patients. Linkage analysis was carried out with 39 microsatellite markers for the HPC1 region and 22 markers for the HPCX region. The maximum two-point LOD score for the HPCX was 2.05 (marker DXS1205, at theta = 0.14), whereas HPC1 LOD scores were all negative. In HOMOG3R analyses, significant evidence of heterogeneity was observed. Subgroup analyses performed to explore the nature of this heterogeneity indicated that families with no male-to-male (NMM) transmission and a late age of diagnosis (>65 years) accounted for most of the HPCX-linked cases. The maximum HPCX LOD score in this subgroup was 3.12 (theta = 0.001). Nonparametric sibling pair analyses gave a peak LOD score of 3.04 (P < 0.000093) for the NMM transmission subgroup. No subgroup showed any positivity for HPC1. This study suggests that the HPCX-linked prostate cancer families represent a distinct subgroup characterized by NMM transmission of disease and late age of diagnosis.
已经提出了几个遗传性前列腺癌（HPC）的易感基因座，包括位于1q24 - q25的HPC1（OMIM #601518）和位于Xq27 - q28的HPCX（OMIM #300147）。基因同质的人群，如芬兰人群，以及不同的家系亚组，可能有助于最小化使复杂性状的基因剖析复杂化的遗传异质性。在此，研究了HPC1和HPCX基因座在一系列芬兰前列腺癌家系中的作用，特别是在按年龄、患病例数和疾病传播方式定义的家系亚组中。从57个至少有两名在世前列腺癌患者的芬兰HPC家系中收集了DNA样本。对HPC1区域用39个微卫星标记，对HPCX区域用22个标记进行连锁分析。HPCX的最大两点LOD分数为2.05（标记DXS1205，θ = 0.14），而HPC1的LOD分数均为阴性。在HOMOG3R分析中，观察到显著的异质性证据。为探索这种异质性的本质而进行的亚组分析表明，无男性对男性（NMM）传播且诊断年龄较晚（>65岁）的家系占大多数与HPCX连锁的病例。该亚组中的最大HPCX LOD分数为3.12（θ = 0.001）。非参数同胞对分析给出NMM传播亚组的峰值LOD分数为3.04（P < 0.000093）。没有亚组显示HPC1有任何阳性结果。这项研究表明，与HPCX连锁的前列腺癌家系代表了一个独特的亚组，其特征为疾病的NMM传播和诊断年龄较晚。
