前列腺癌家族与Xq27 - 28的遗传连锁分析。

Genetic linkage analysis of prostate cancer families to Xq27-28.

作者信息

Peters M A, Jarvik G P, Janer M, Chakrabarti L, Kolb S, Goode E L, Gibbs M, DuBois C C, Schuster E F, Hood L, Ostrander E A, Stanford J L

机构信息

Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.

出版信息

Hum Hered. 2001;51(1-2):107-13. doi: 10.1159/000022965.

DOI:10.1159/000022965

PMID:11096277

Abstract

OBJECTIVES

A recent linkage analysis of 360 families at high risk for prostate cancer identified the q27-28 region on chromosome X as the potential location of a gene involved in prostate cancer susceptibility. Here we report on linkage analysis at this putative HPCX locus in an independent set of 186 prostate cancer families participating in the Prostate Cancer Genetic Research Study (PROGRESS).

METHODS

DNA samples from these families were genotyped at 8 polymorphic markers spanning 14.3 cM of the HPCX region.

RESULTS

Two-point parametric analysis of the total data set resulted in positive lod scores at only two markers, DXS984 and DXS1193, with scores of 0.628 at a recombination fraction (theta) of 0.36 and 0.012 at theta = 0.48, respectively. The stratification of pedigrees according to the assumed mode of transmission increased the evidence of linkage at DXS984 in 81 families with no evidence of male-to-male transmission (lod = 1.062 at theta = 0.28).

CONCLUSIONS

Although this analysis did not show statistically significant evidence for the linkage of prostate cancer susceptibility to Xq27-28, the results are consistent with a small percentage of families being linked to this region. The analysis further highlights difficulties in replicating linkage results in an etiologically heterogeneous, complexly inherited disease.

摘要

目的

最近一项对360个前列腺癌高危家族的连锁分析确定，X染色体上的q27 - 28区域是一个与前列腺癌易感性相关基因的潜在位置。在此，我们报告了在参与前列腺癌遗传研究（PROGRESS）的186个前列腺癌家族的独立样本中，对这个假定的HPCX基因座进行的连锁分析。

方法

对这些家族的DNA样本在跨越HPCX区域14.3 cM的8个多态性标记处进行基因分型。

结果

对整个数据集进行两点参数分析时，仅在两个标记DXS984和DXS1193处得到了正的连锁值，在重组率（θ）为0.36时，DXS984的连锁值为0.628，在θ = 0.48时，DXS1193的连锁值为0.012。根据假定的遗传模式对家系进行分层，增加了在81个无男性对男性遗传证据的家系中DXS984处的连锁证据（在θ = 0.28时，连锁值 = 1.062）。