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前列腺癌全基因组关联研究综述。

A Review of Prostate Cancer Genome-Wide Association Studies (GWAS).

机构信息

The Institute of Cancer Research, Sutton, United Kingdom.

出版信息

Cancer Epidemiol Biomarkers Prev. 2018 Aug;27(8):845-857. doi: 10.1158/1055-9965.EPI-16-1046. Epub 2018 Jan 18.

Abstract

Prostate cancer is the most common cancer in men in Europe and the United States. The genetic heritability of prostate cancer is contributed to by both rarely occurring genetic variants with higher penetrance and moderate to commonly occurring variants conferring lower risks. The number of identified variants belonging to the latter category has increased dramatically in the last 10 years with the development of the genome-wide association study (GWAS) and the collaboration of international consortia that have led to the sharing of large-scale genotyping data. Over 40 prostate cancer GWAS have been reported, with approximately 170 common variants now identified. Clinical utility of these variants could include strategies for population-based risk stratification to target prostate cancer screening to men with an increased genetic risk of disease development, while for those who develop prostate cancer, identifying genetic variants could allow treatment to be tailored based on a genetic profile in the early disease setting. Functional studies of identified variants are needed to fully understand underlying mechanisms of disease and identify novel targets for treatment. This review will outline the GWAS carried out in prostate cancer and the common variants identified so far, and how these may be utilized clinically in the screening for and management of prostate cancer. .

摘要

前列腺癌是欧洲和美国男性中最常见的癌症。前列腺癌的遗传易感性是由具有较高外显率的罕见遗传变异和赋予较低风险的中度至常见变异共同贡献的。在过去的 10 年中,随着全基因组关联研究(GWAS)的发展以及国际合作组织的合作,导致了大规模基因分型数据的共享,属于后者类别的已鉴定变异数量急剧增加。已经报道了超过 40 项前列腺癌 GWAS,现在已经确定了大约 170 个常见变异。这些变异的临床应用可能包括基于人群的风险分层策略,将前列腺癌筛查针对疾病发展遗传风险增加的男性,而对于那些患有前列腺癌的男性,确定遗传变异可以根据早期疾病中的遗传特征来调整治疗方法。需要对已鉴定的变异进行功能研究,以充分了解疾病的潜在机制并确定治疗的新靶点。这篇综述将概述迄今为止在前列腺癌中进行的 GWAS 和已确定的常见变异,以及它们如何在前列腺癌的筛查和管理中在临床上得到利用。

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