实现癌症易感性基因的承诺。
Realizing the promise of cancer predisposition genes.
机构信息
1] Division of Genetics and Epidemiology, Institute of Cancer Research, London SW2 5NG, UK. [2] Cancer Genetics Unit, Royal Marsden Hospital Foundation Trust, London SM2 5PT, UK.
出版信息
Nature. 2014 Jan 16;505(7483):302-8. doi: 10.1038/nature12981.
Abstract
Genes in which germline mutations confer highly or moderately increased risks of cancer are called cancer predisposition genes. More than 100 of these genes have been identified, providing important scientific insights in many areas, particularly the mechanisms of cancer causation. Moreover, clinical utilization of cancer predisposition genes has had a substantial impact on diagnosis, optimized management and prevention of cancer. The recent transformative advances in DNA sequencing hold the promise of many more cancer predisposition gene discoveries, and greater and broader clinical applications. However, there is also considerable potential for incorrect inferences and inappropriate clinical applications. Realizing the promise of cancer predisposition genes for science and medicine will thus require careful navigation.
摘要
种系基因突变赋予个体高度或中度癌症风险的基因被称为癌症易感基因。已经发现了 100 多种此类基因，这些基因在许多领域提供了重要的科学见解，尤其是在癌症发病机制方面。此外，癌症易感基因的临床应用对癌症的诊断、优化管理和预防产生了重大影响。最近 DNA 测序的突破性进展有望发现更多的癌症易感基因，并带来更广泛的临床应用。然而，也存在着错误推断和不适当的临床应用的巨大风险。因此，为了科学和医学的发展，要充分发挥癌症易感基因的潜力，就需要谨慎地进行探索。
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本文引用的文献
1
Signatures of mutational processes in human cancer.人类癌症中的突变过程特征。
Nature. 2013 Aug 22;500(7463):415-21. doi: 10.1038/nature12477. Epub 2013 Aug 14.
2
A systematic review of cancer GWAS and candidate gene meta-analyses reveals limited overlap but similar effect sizes.一项癌症 GWAS 和候选基因荟萃分析的系统回顾显示，两者的重叠有限，但效应大小相似。
Eur J Hum Genet. 2014 Mar;22(3):402-8. doi: 10.1038/ejhg.2013.161. Epub 2013 Jul 24.
3
Chemoprevention in Lynch syndrome.林奇综合征的化学预防。
Fam Cancer. 2013 Dec;12(4):707-18. doi: 10.1007/s10689-013-9650-y.
4
Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome.慢病毒造血干细胞基因治疗 Wiskott-Aldrich 综合征患者。
Science. 2013 Aug 23;341(6148):1233151. doi: 10.1126/science.1233151. Epub 2013 Jul 11.
5
Risks and benefits of screening asymptomatic women for ovarian cancer: a systematic review and meta-analysis.筛查无症状女性卵巢癌的风险和获益：系统评价和荟萃分析。
Gynecol Oncol. 2013 Sep;130(3):674-81. doi: 10.1016/j.ygyno.2013.06.029. Epub 2013 Jun 30.
6
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7
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J Clin Endocrinol Metab. 2013 Aug;98(8):3149-64. doi: 10.1210/jc.2013-1204. Epub 2013 Jun 6.
8
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Eur J Cancer. 2013 Jul;49(11):2531-41. doi: 10.1016/j.ejca.2013.04.005. Epub 2013 May 3.
10
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