Evaluation of linkage and association of HPC2/ELAC2 in patients with familial or sporadic prostate cancer.
Evaluation of linkage and association of HPC2/ELAC2 in patients with familial or sporadic prostate cancer.
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家族性或散发性前列腺癌患者中 HPC2/ELAC2 连锁和关联的评估。
DOI：
10.1086/319513
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发表时间：
2001
影响因子：
9.8
通讯作者：
Isaacs,WB
中科院分区：
文献类型：
--
作者：
Xu,J;Zheng,SL;Carpten,JD;Nupponen,NN;Robbins,CM;Mestre,J;Moses,TY;Faith,DA;Kelly,BD;Isaacs,SD;Wiley,KE;Ewing,CM;Bujnovszky,P;Chang,B;Bailey-Wilson,J;Bleecker,ER;Walsh,PC;Trent,JM;Meyers,DA;Isaacs,WB
为探讨HPC 2/ELAC 2与前列腺癌的关系，我们对159个遗传性前列腺癌（HPC）家系进行了HPC 2/ELAC 2基因17 p11区及其周围6个标记的连锁分析，对93个HPC先证者进行了HPC 2/ELAC 2基因所有编码外显子的突变筛查分析，并对HPC 2/ELAC 2基因17 p11区及其周围6个标记的突变情况进行了分析。（3）在159例HPC先证者、249例散发性前列腺癌患者和222例健康男性对照者中进行基于家族和基于人群的常见HPC 2/ELAC 2错义变异的关联研究。在总样本中没有发现连锁的证据，也没有在任何基于发病年龄、患病成员数量、男性对男性疾病传播或种族等特征的谱系子集中发现连锁的证据。此外，通过对93例HPC先证者的所有HPC 2/ELAC外显子进行突变分析，仅发现了两个先前报道的错义突变（Ser 217 Leu和Ala 541 Thr）。在相关性分析中，基于家族的检测没有发现Leu 217和/或Thr 541等位基因向受影响后代的过度传播，基于人群的检测也没有发现前列腺癌患者和对照组之间两种多态性的等位基因频率存在任何统计学显著差异。这项研究的结果使我们拒绝了三个备选假设：（1）在17 p11处的高度外显的主要前列腺癌易感基因，（2）HPC 2/ELAC 2的等位基因变体Leu 217或Thr 541是高外显率突变，（3）变体Leu 217或Thr 541是低外显率的风险修饰等位基因。然而，我们确实观察到患者中Leu 217纯合子携带率高于对照受试者的趋势。考虑到遗传异质性、表型复制和不完全突变对前列腺癌连锁和关联研究的影响，以及对我们研究样本中检测连锁和关联的能力的影响，我们的结果不能排除在该位点高度外显的前列腺癌基因仅在少数家系中分离的可能性。我们也不能排除前列腺癌修饰基因，它赋予的风险低于报告。需要更多更大规模的研究来更全面地评估该基因在前列腺癌风险中的作用。
To investigate the relationship between HPC2/ELAC2 and prostate cancer risk, we performed the following analyses: (1) a linkage study of six markers in and around the HPC2/ELAC2 gene at 17p11 in 159 pedigrees with hereditary prostate cancer (HPC); (2) a mutation-screening analysis of all coding exons of the gene in 93 probands with HPC; (3) family-based and population-based association study of common HPC2/ELAC2 missense variants in 159 probands with HPC, 249 patients with sporadic prostate cancer, and 222 unaffected male control subjects. No evidence for linkage was found in the total sample, nor in any subset of pedigrees based on characteristics that included age at onset, number of affected members, male-to-male disease transmission, or race. Furthermore, only the two previously reported missense changes (Ser217Leu and Ala541Thr) were identified by mutational analysis of all HPC2/ELAC exons in 93 probands with HPC. In association analyses, family-based tests did not reveal excess transmission of the Leu217 and/or Thr541 alleles to affected offspring, and population-based tests failed to reveal any statistically significant difference in the allele frequencies of the two polymorphisms between patients with prostate cancer and control subjects. The results of this study lead us to reject the three alternative hypotheses of (1) a highly penetrant, major prostate cancer–susceptibility gene at 17p11, (2) the allelic variants Leu217 or Thr541 of HPC2/ELAC2 as high-penetrance mutations, and (3) the variants Leu217 or Thr541 as low-penetrance, risk-modifying alleles. However, we did observe a trend of higher Leu217 homozygous carrier rates in patients than in control subjects. Considering the impact of genetic heterogeneity, phenocopies, and incomplete penetrance on the linkage and association studies of prostate cancer and on the power to detect linkage and association in our study sample, our results cannot rule out the possibility of a highly penetrant prostate cancer gene at this locus that only segregates in a small number of pedigrees. Nor can we rule out a prostate cancer–modifier gene that confers a lower-than-reported risk. Additional larger studies are needed to more fully evaluate the role of this gene in prostate cancer risk.
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影响因子：
9.8
作者：
Gibbs, M;Stanford, JL;Ostrander, EA
通讯作者：
Ostrander, EA
影响因子：
1.9
作者：
CLERGETDARPOUX, F;BONAITIPELLIE, C;HOCHEZ, J
通讯作者：
HOCHEZ, J
影响因子：
9.8
作者：
Xu, JF
通讯作者：
Xu, JF
影响因子：
9.8
作者：
Berry, R;Schroeder, JJ;Schaid, DJ
通讯作者：
Schaid, DJ
影响因子：
9.8
作者：
Kong, A;Cox, NJ
通讯作者：
Cox, NJ