Balancing benefits, costs, and harms: policy implications of expanding cancer susceptibility testing from genetics clinics to the general population.

This expansion positions germline pathogenic variants in cancer susceptibility genes and polygenic risk scores as crucial tools for precision prevention, surveillance, and early detection.

这种扩展将遗传性致病变异和多基因风险评分定位为精准预防、监测和早期检测的关键工具。

However, implementation has outpaced the evidence needed to justify testing at scale, particularly in well populations.

然而，实施的速度已经超过了证明大规模检测合理性的证据，特别是在健康人群中。

For a small number of first-wave genes-including BRCA1, BRCA2, MLH1, and MSH2-cancer risks are well established and downstream medical interventions are supported by substantial observational evidence, albeit with an absence of randomised trials.

对于少数第一批基因，包括BRCA1、BRCA2、MLH1和MSH2，癌症风险已经得到很好的确立，下游的医疗干预得到了大量的观察性证据支持，尽管缺乏随机试验。

Contrastingly, for many later discovered genes now included on multigene panels, penetrance estimates remain uncertain, variant-specific risks are poorly resolved, and evidence is scarce or absent regarding mortality reduction, quality of life benefit, or cost-effectiveness for the recommended downstream interventions.

相比之下，对于许多后来发现并被纳入多基因面板的基因，穿透率估计仍然不确定，变异特异性风险尚未明确解决，关于推荐的下游干预措施在减少死亡率、提高生活质量或成本效益方面的证据稀缺或缺失。

Polygenic risk scores offer promise for stratified prevention, but their discriminatory capacity is constrained, performance is ancestry dependent, and clinical utility remains uncertain in most settings.

多基因风险评分有望实现分层预防，但其区分能力受限，表现依赖于祖先，且在大多数情况下，其临床效用仍然不确定。

Building on the Lancet Oncology Commission on cancer genomics and precision oncology, this Policy Review examines the evidentiary, clinical, and health-system challenges associated with cancer susceptibility testing across clinical care and public health prevention.

基于《柳叶刀肿瘤学》关于癌症基因组学和精准肿瘤学的委员会报告，本政策审查探讨了在临床护理和公共卫生预防中与癌症易感性检测相关的证据、临床和卫生系统挑战。

We argue that the value of such testing should be assessed in terms of its clinical value and public health utility, with careful attention to the context in which testing is offered.

我们认为，这种检测的价值应该根据其临床价值和公共卫生效用进行评估，同时仔细考虑提供检测的背景。

We propose a tiered, context-specific approach to implementation, aimed at distinguishing settings in which susceptibility testing could provide a net benefit from those scenarios in which its use should remain restricted, highly selective, or confined to research.

我们提出了一种分层的、特定于情境的实施方法，旨在区分那些耐药性检测可能带来净效益的环境，以及那些应限制使用、高度选择性使用或仅限于研究的情景。