A major locus for hereditary prostate cancer in Finland:: localization by linkage disequilibrium of a haplotype in the HPCX region
A major locus for hereditary prostate cancer in Finland:: localization by linkage disequilibrium of a haplotype in the HPCX region
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DOI：
10.1007/s00439-005-1306-z
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发表时间：
2005-08-01
期刊：
影响因子：
5.3
通讯作者：
Bailey-Wilson, JE
中科院分区：
文献类型：
--
作者：
Baffoe-Bonnie, AB;Smith, JB;Bailey-Wilson, JE
背景：前列腺癌（PRCA）是西方国家男性最常见的癌症。在芬兰，PRCA的年龄调整发病率为每10万人81.5人。我们以前报道过，在芬兰，PRCA“非男性对男性”（NMM）传播的家庭中的迟发病例占与HPCX区域（Xq 27 -28）的大部分联系。本研究的目的是检测遗传性前列腺癌（HPC）家族病例和人群对照之间的连锁不平衡（LD）和标记DXS 1205周围的单倍型共享。在108例PRCA病例和257例人群对照之间进行了Xq 26 -28区域中23个标记物的基因分型的初始等位基因关联。这导致标记物DXS 1205的等位基因“180”的高度显著的标称单侧Fisher精确P值为0.0003。随后，当比较60例NMM病例和257例对照时，对于标记物DXS 1205的相同等位基因观察到相似的显著性水平（P = 0.0002）。这些结果在Bonferroni校正多重检验后仍然显著。精细定位工作包括四个额外标记D3 S2390、bG82i1.9、bG82i1.1、bG82i1.0和四个单核苷酸多态性（SNP）的基因分型，以增加DXS 1205周围的原始标记。结果：我们的主要发现是，从“D3 S2390”到“bG82i1.0”的标记位于关键位点的两侧，约150 kb。Levin和Bertell的LD测量（delta），一个可能的变体的定位指南，对于标记bG82i1.9和DXS 1205的等位基因分别为0.42和0.41。结论：在本研究中，最显著的单倍型包括三个紧密连锁的连续标记：在几个可能的单倍型中的“cen-bG 82 i1.9-SNP-Hap B-bG 82 i1.1-tel”[“197-2- 234”]（标称Fisher单侧P=0.003）。在此区间内映射的两个转录单位是LDOC 1和SPAN XC基因。Xq 26 -28区域的探索促进了HPCX基因的定位克隆。这项研究代表了第一份报告，确定了在Xq 27 -28区域的HPCX和X-连锁前列腺癌之间的关联，在芬兰人群中没有男性对男性的传播。
Background: Prostate cancer (PRCA) is the most common cancer in males in the western world. In Finland PRCA has an age-adjusted incidence of 81.5 per 100,000. We previously reported that in Finland, the late-onset cases in families with "no-male-to-male'' (NMM) transmission of PRCA accounted for most of the linkage to the HPCX region (Xq27-28). The aim of the present study was to test for linkage disequilibrium (LD) and haplotype-sharing around marker DXS1205 between cases from hereditary prostate cancer (HPC) families and population controls. The initial allelic association was performed between 108 PRCA cases and 257 population controls genotyped for 23 markers in the Xq26-28 region. This resulted in a highly significant nominal one-sided Fisher's exact P-value of 0.0003 for allele "180'' of marker DXS1205. Subsequently, a similar level of significance was observed for the same allele for marker DXS1205 (P = 0.0002) when comparing 60 NMM cases and 257 controls. These results were still significant after Bonferroni correction for multiple testing. Fine mapping efforts included the genotyping of four additional markers D3S2390, bG82i1.9, bG82i1.1, bG82i1.0 and four single nucleotide polymorphisms ( SNPs) to augment the original markers around DXS1205. Results: Our major finding is that markers extending from "D3S2390'' to "bG82i1.0'' flank the critical locus, about 150 kb. Levin and Bertell's LD measure (delta), a guide to localization of a possible variant, was 0.42 and 0.41 for alleles of markers bG82i1.9 and DXS1205, respectively. Conclusions: In this study, the most significant haplotype comprised the three tightly linked, contiguous markers: "cen-bG82i1.9-SNP-Hap B-bG82i1.1-tel'' ["197-2-234''] among several possible haplotypes ( nominal Fisher's one-sided P=0.003). The two transcription units mapping within this interval are the LDOC1 and SPANXC genes. Positional cloning of the HPCX gene(s) is being facilitated by this exploration of the Xq26-28 region. This study represents the first report identifying a haplotype in the Xq27-28 region for an association between HPCX and X-linked prostate cancer with no-male-to-male transmission in the Finnish population.