Systematic evaluation of genetic variation at the androgen receptor locus and risk of prostate cancer in a multiethnic cohort study
Systematic evaluation of genetic variation at the androgen receptor locus and risk of prostate cancer in a multiethnic cohort study
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DOI：
10.1086/427224
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发表时间：
2005-01-01
影响因子：
9.8
通讯作者：
Altshuler, D
中科院分区：
文献类型：
--
作者：
Freedman, ML;Pearce, CL;Altshuler, D
雄激素受体（AR）基因外显子1中CAG微卫星多态性的重复长度与人类前列腺癌的风险相关。这种关联已经成为超过120篇主要流行病学出版物和多篇综述文章的焦点，但一致和可重复的关联尚未得到证实。我们在一项多种族、前瞻性前列腺癌队列研究中系统地解决了超过4，000名个体中假阴性和假阳性关联的可能原因，通过微卫星基因分型、晚期癌症病例中外显子的直接重新测序和单倍型全面研究了遗传变异。180-kb AR基因组位点的分析。这些数据未能证实AR基因位点的常见遗传变异影响前列腺癌的风险。一种系统的方法，评估编码和非编码的遗传变异在大规模和多样化的患者样本可以帮助澄清有关遗传变异和疾病之间的关联的假设。
Repeat length of the CAG microsatellite polymorphism in exon 1 of the androgen receptor (AR) gene has been associated with risk of prostate cancer in humans. This association has been the focus of greater than 120 primary epidemiological publications and multiple review articles, but a consistent and reproducible association has yet to be confirmed. We systematically addressed possible causes of false-negative and false-positive association in greater than 4,000 individuals from a multiethnic, prospective cohort study of prostate cancer, comprehensively studying genetic variation by microsatellite genotyping, direct resequencing of exons in advanced cancer cases, and haplotype analysis across the 180-kb AR genomic locus. These data failed to confirm that common genetic variation in the AR gene locus influences risk of prostate cancer. A systematic approach that assesses both coding and noncoding genetic variation in large and diverse patient samples can help clarify hypotheses about association between genetic variants and disease.