Combined analysis of hereditary prostate cancer linkage to 1q24-25:: Results from 772 hereditary prostate cancer families from the International Consortium For Prostate Cancer Genetics
Combined analysis of hereditary prostate cancer linkage to 1q24-25:: Results from 772 hereditary prostate cancer families from the International Consortium For Prostate Cancer Genetics
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DOI：
10.1086/302807
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发表时间：
2000-03-01
影响因子：
9.8
通讯作者：
Xu, JF
中科院分区：
文献类型：
--
作者：
Xu, JF
先前的一项连锁研究提供了前列腺癌易感位点1q24-25的证据。随后对其他家庭收集的报告得出了相互矛盾的结果。此外，通过鉴定Xq27-28、1q42-43和1p36上其他推测的遗传性前列腺癌位点，也提供了基因座异质性的证据。本研究对来自北美、澳大利亚、芬兰、挪威、瑞典和英国的国际前列腺癌遗传学协会（ICPCG）成员确定的772个遗传性前列腺癌家族的1q24-25区域的6个标记进行了综合分析。总体而言，有一些证据表明存在关联，在D1S212时，峰值参数多点LOD评分假设异质性（HLOD）为1.40 （P = 0.01）。与该位点有关的家庭(a)的估计比例为。06 （1-LOD支持间隔0.01 - 0.12）。这一证据没有通过非参数方法观察到，可能是因为广泛的异质性。进一步的参数分析揭示了家庭内男性间疾病传播的显著影响。在491个这样的家庭中，峰值HLOD为2.56 (P = 0.0006), alpha = 0.11（1-LOD支持区间为0.04 ~ 0.19），其余281个家庭的hlod为0。在有男性间疾病传播的家庭中，a随着诊断时平均年龄的早期而增加(
A previous linkage study provided evidence for a prostate cancer-susceptibility locus at 1q24-25. Subsequent reports in additional collections of families have yielded conflicting results. In addition, evidence for locus heterogeneity has been provided by the identification of other putative hereditary prostate cancer loci on Xq27-28, 1q42-43, and 1p36. The present study describes a combined analysis for six markers in the 1q24-25 region in 772 families affected by hereditary prostate cancer and ascertained by the members of the International Consortium for Prostate Cancer Genetics (ICPCG) from North America, Australia, Finland, Norway, Sweden, and the United Kingdom. Overall, there was some evidence for linkage, with a peak parametric multipoint LOD score assuming heterogeneity (HLOD) of 1.40 (P = .01) at D1S212. The estimated proportion of families (a) linked to the locus was .06 (1-LOD support interval .01-.12). This evidence was not observed by a nonparametric approach, presumably because of the extensive heterogeneity. Further parametric analysis revealed a significant effect of the presence of male-to-male disease transmission within the families. In the subset of 491 such families, the peak HLOD was 2.56 (P = .0006) and alpha =.11 (1-LOD support interval .04-.19), compared with HLODs of 0 in the remaining 281 families. Within the families with male-to-male disease transmission, a increased with the early mean age at diagnosis (