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开发和验证肺癌多基因风险评分,包括对风险因素的敏感性变异

Zhimin Ma¹, Zhaopeng Zhu¹, Guanlian Pang¹

¹Department of Epidemiology, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

International journal of cancer

|October 8, 2024

概括

一个新的元多基因风险评分 (metaPRS) 通过整合风险因素的遗传变异来改善肺癌风险预测. 这种增强的遗传风险评估完善了肺癌患者分层.

科学领域:

遗传学遗传学是一个
在瘤学瘤学.
流行病学流行病学

背景情况:

多基因风险评分 (PRS) 可以通过结合风险因素的遗传变异来提高,以改善疾病风险预测.
这种方法对肺癌风险预测和分层的有效性尚未完全阐明.

研究的目的:

通过整合多个PRS来开发肺癌的元多基因风险评分 (metaPRS).
评估metaPRS对肺癌风险的预测性能及其在风险分层中的实用性.

主要方法:

开发了九种肺癌PRS,三种组织病理学亚型和17种相关风险因素,使用2180种遗传变异.
在英国生物库 (N=442,508) 中使用弹性网考克斯回归将这些PRS集成到metaPRS中.
在前列腺癌,肺癌,结肠直肠癌和卵巢癌 (PLCO) 查试验中评估了metaPRS预测效应 (N=108,665).

主要成果:

甲基PRS与肺癌风险有显著的关联 (HR=1.33每SD增加).
在PLCO试验中,metaPRS与单个PRS (0.513-0.564) 相比,获得了更高的C指数 (0.580).
将metaPRS整合到临床风险模型中改善了风险重新分类 (连续NRI=6.50%) 并确定了仅通过临床模型错过的高风险个体.

结论:

与传统的PRS相比,开发的metaPRS提高了肺癌风险预测.
metaPRS提供了改进的风险分层能力,特别是用于识别需要更密切监测的个人.
这种方法有望改进个性化肺癌查和预防策略.

关键词:

肺癌是一种肺癌.超多基因风险评分 (meta polygenic risk score) 是指多基因的风险评分.多基因风险评分多基因风险评分.风险预测风险预测

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