Johanneson Bo, Deutsch Kerry, McIntosh Laura, Friedrichsen-Karyadi Danielle M, Janer Marta, Kwon Erika M, Iwasaki Lori, Hood Leroy, Ostrander Elaine A, Stanford Janet L
Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Prostate. 2007 May 15;67(7):732-42. doi: 10.1002/pros.20528.
The Seattle-based PROGRESS study was started in 1995 to ascertain hereditary prostate cancer (HPC) families for studies of genetic susceptibility. Subsequent studies by several research groups, including our own, suggest that HPC is a genetically heterogeneous disease. To be successful in mapping loci for such a complex disease, one must consider ways of grouping families into subsets that likely share the same genetic origin. Towards that end, we analyzed a genome-wide scan of HPC families with primary kidney cancer.
An 8.1 cM genome-wide scan including 441 microsatellite markers was analyzed by both parametric and non-parametric linkage approaches in fifteen HPC families with the co-occurrence of kidney cancer.
There was no evidence for significant linkage in the initial findings. However, two regions of suggestive linkage were observed at 11q12 and 4q21, with HLOD scores of 2.59 and 2.10, respectively. The primary result on chromosome 11 was strengthened after excluding two families with members who had rare transitional cell carcinoma (TCC). Specifically, we observed a non-parametric Kong and Cox P-value of 0.004 for marker D11S1290 at 11p11.2. The 8 cM region between 11p11.2 and 11q12.2 was refined by the addition of 16 new markers. The subset of HPC families with a median age of diagnosis >65 years demonstrated the strongest evidence for linkage, with an HLOD = 2.50. The P-values associated with non-parametric analysis ranged from 0.004 to 0.05 across five contiguous markers.
Analysis of HPC families with members diagnosed with primary renal cell carcinoma demonstrates suggestive linkage to chromosome 11p11.2-q12.2.
基于西雅图的PROGRESS研究始于1995年，旨在确定遗传性前列腺癌（HPC）家族以进行遗传易感性研究。包括我们自己在内的几个研究小组随后进行的研究表明，HPC是一种遗传异质性疾病。要成功定位此类复杂疾病的基因座，必须考虑将家族分组为可能具有相同遗传起源的亚组的方法。为此，我们分析了患有原发性肾癌的HPC家族的全基因组扫描。
通过参数和非参数连锁方法，对15个同时患有肾癌的HPC家族进行了包含441个微卫星标记的8.1 cM全基因组扫描分析。
最初的研究结果中没有显著连锁的证据。然而，在11q12和4q21观察到两个提示性连锁区域，HLOD分数分别为2.59和2.10。在排除两个家庭成员患有罕见移行细胞癌（TCC）的家族后，11号染色体上的主要结果得到了加强。具体而言，我们在11p11.2处的标记D11S1290观察到非参数Kong和Cox P值为0.004。通过添加16个新标记，对11p11.2和11q12.2之间的8 cM区域进行了细化。诊断中位年龄>65岁的HPC家族亚组显示出最强的连锁证据，HLOD = 2.50。在五个连续标记中，与非参数分析相关的P值范围为0.004至0.05。
对家庭成员被诊断患有原发性肾细胞癌的HPC家族进行分析，表明与11p11.2 - q12.2染色体存在提示性连锁。
Zotero 插件