Are polygenic risk scores ready for the cancer clinic?-a perspective.
Are polygenic risk scores ready for the cancer clinic?-a perspective.
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DOI：
10.21037/tlcr-21-698
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发表时间：
2022-05
影响因子：
4
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中科院分区：
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为了实现复杂疾病精准医疗的目标，需要有区分性的临床风险模型。已提出的一种方法是多基因风险评分（PRS）。 PRS 包含有关癌症遗传风险的信息，特别是人群中常见的遗传变异。虽然 PRS 显然与癌症风险相关，但将 PRS 纳入临床实践是否有用仍存在争议。在这里，我们向癌症诊所提出这一重要的讨论。我们认为，在癌症中，PRS 的临床效用将取决于它们的可操作性，或者这样的评分如何指导临床实践。反过来，可操作性取决于几个因素。首先，可操作性取决于评分的区分能力，或者它预测谁有患病风险的程度。其次，这取决于它们相对于现有实践的比较表现，因为如果临床中使用更好的预测因子，具有良好区分能力的分数将没有用处。最后，为了使 PRS 发挥作用，还必须有可用的预防措施。我们讨论了在每个标准的背景下利用 PRS 的优势和挑战，并提供了将 PRS 转化为癌症临床所需的见解。我们进一步认为，在未来的研究中，除了预测癌症风险之外，类似开发的 PRS 模型可能有助于预测预后或治疗耐药性。
To realize the goals of precision medicine in complex disease, discriminative clinical risk models are needed. One approach that has been proposed is polygenic risk scores (PRSs). PRSs incorporate information about inherited genetic risk for cancer, specifically those genetic variants that are common in the population. While PRSs are clearly associated with risk of cancer, there is an on-going debate on whether integrating PRSs into clinical practice have utility. Here, we present this important discussion to the cancer clinic. We argue that in cancer, the clinical utility of PRSs will depend on their actionability, or how such a score may guide clinical practice. In turn, the actionability depends on several factors. First, actionability depends on the discriminative power of the score, or how well it predicts who is at risk of the disease. Second, it depends on their comparative performance with respect to existing practice, as a score with good discriminative power will not be useful if there are better predictors used in the clinic. Finally, for a PRS to be useful there must also be available preventive actions. We discuss the strengths and challenges of utilizing a PRS in the context of each of these criteria, and provide insights on what is needed towards moving forward in translating PRSs into the cancer clinic. We further argue that in future studies, beyond predicting cancer risk, similarly developed PRS models may be of utility in predicting prognosis or treatment resistance.