我们的概念验证研究揭示了年龄、多基因风险评分（PRS）和非基因风险因素共同作用的风险分层潜力，可提升快速出现的非侵入性多癌症早期检测（MCED）液态活检测试的风险-收益平衡。我们开发并验证了性别特异性泛癌症风险评分（PCRS），由身体质量指数、吸烟、家族癌症史和特定癌症基因风险评分（PRS）的组合定义，以预测至少患上多种常见癌症之一的绝对风险。我们演示了PRS在改善仅考虑风险因素模型的预测性能方面的附加价值，并展示了根据年龄和PCRS定义的风险层中两种有前途的多癌症筛查测试的正负预测值。© 2023. 作者（们）。

Our proof-of-concept study reveals the potential of risk stratification by the combined effects of age, polygenic risk scores (PRS), and non-genetic risk factors in increasing the risk-benefit balance of rapidly emerging non-invasive multicancer early detection (MCED) liquid biopsy tests. We develop and validate sex-specific pan-cancer risk scores (PCRSs), defined by the combination of body mass index, smoking, family history of cancers, and cancer-specific polygenic risk scores (PRSs), to predict the absolute risk of developing at least one of the many common cancer types. We demonstrate the added value of PRSs in improving the predictive performance of the risk factors only model and project the positive and negative predictive values for two promising multicancer screening tests across risk strata defined by age and PCRS.© 2023. The Author(s).