Briggs Sarah, Slade Ingrid
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN UK.
2Wellcome Centre for Ethics and Humanities and Ethox Centre, Nuffield Department of Population Health, Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Old Road Campus, Oxford, OX3 7LF UK.
Curr Genet Med Rep. 2019;7(2):63-74. doi: 10.1007/s40142-019-00162-x. Epub 2019 May 18.
As the costs of genomic testing have fallen, and our understanding of genetic susceptibility to cancers has grown, there has been increasing interest in incorporating testing for cancer susceptibility genes, and polygenic risk estimates, into population cancer screening. A growing body of evidence suggests that this would be both clinically and cost-effective. In this article, we aim to explore the frameworks used to evaluate screening programmes, evaluate whether population screening for cancer susceptibility can be assessed using these standards, and consider additional issues and outcomes of importance in this context.
There are tensions between traditional approaches of genetic testing (utilising tests with high sensitivity and specificity) and the principles of population screening (in which the screening test typically has low specificity), as well as the frameworks used to evaluate the two. Despite the existence of many screening guidelines, including consensus papers, these often do not align fully with broader considerations of genetic test evaluation. Population screening for genetic risk in cancer shifts the focus from diagnostics to prognostication and has wider implications for personal and familial health than existing screening programmes. In addition, understanding of the prevalence and penetrance of cancer susceptibility genes, required by many screening guidelines, may only be obtainable through population-level testing; prospective multi-disciplinary research alongside implementation will be essential.
Appropriate evaluation of genetic screening for cancer risk will require modification of existing screening frameworks to incorporate additional complexity of outcomes and population values. As evidence supporting population screening for cancer susceptibility mounts, development of an appropriate evaluative framework, and expansion of public dialogue will be key to informing policy.
综述目的：随着基因检测成本的下降，以及我们对癌症遗传易感性的认识不断提高，将癌症易感基因检测和多基因风险评估纳入人群癌症筛查的兴趣日益浓厚。越来越多的证据表明，这在临床和成本效益方面都将是可行的。在本文中，我们旨在探讨用于评估筛查项目的框架，评估是否可以使用这些标准对人群癌症易感性筛查进行评估，并考虑在此背景下其他重要的问题和结果。
最新发现：基因检测的传统方法（使用具有高灵敏度和特异性的检测）与人群筛查原则（其中筛查检测通常具有低特异性）之间存在矛盾，用于评估两者的框架也存在矛盾。尽管存在许多筛查指南，包括共识文件，但这些指南往往与基因检测评估的更广泛考虑因素不完全一致。人群癌症遗传风险筛查将重点从诊断转向预后，对个人和家庭健康的影响比现有筛查项目更广泛。此外，许多筛查指南要求了解癌症易感基因的患病率和外显率，这可能只能通过人群层面的检测获得；前瞻性多学科研究与实施将至关重要。
总结：对癌症风险基因筛查进行适当评估将需要修改现有的筛查框架，以纳入结果和人群价值观的额外复杂性。随着支持人群癌症易感性筛查的证据不断增加，制定适当的评估框架和扩大公众对话将是为政策提供信息的关键。
