多基因风险评分与国家肺部查试验中的肺癌发展和死亡有关
Robert P Young1,2, Raewyn J Scott1, Tom Callender3
1Faculty of Medical and Health Sciences, University of Auckland, Auckland P.O. Box 37-971, New Zealand.
Journal of clinical medicine
|May 14, 2025
概括
多基因风险评分 (PRS) 识别了肺癌死亡风险较高的个体. 这种遗传标记物与吸烟史相结合,可以改善高风险人群的肺癌查策略.
科学领域:
- 遗传学和流行病学
- 癌症研究 癌症研究
- 生物标志物发现发现
背景情况:
- 肺癌的发展受到吸烟和遗传倾向的影响.
- 多基因风险评分 (PRS),聚合多个遗传变异的影响,为风险分层提供了潜在的可能性.
- 在肺癌查队列中,PRS的临床实用性仍未被探索.
研究的目的:
- 在肺癌查人群中评估复合PRS与肺癌发病率和死亡率之间的关联.
- 验证PRS对肺癌死亡率的预测性能,在一个独立的常吸烟者队列中.
主要方法:
- 从国家肺部查试验 (NLST) 中对9,191名高风险吸烟者的特异分析.
- 从12个经过验证的风险基因型中计算一个复合PRS.
- 在英国生物库队列 (N=167,796) 中验证未经查的长期吸烟者.
主要成果:
- 在NLST队列中,PRS与肺癌发病率 (p < 0.0001) 和死亡率 (p = 0.004) 有显著的相关性.
- 升高的PRS与肺癌死亡独立相关 (p = 0.0027).
- 较高的PRS得分 (中等和高) 与较低的PRS相比,与增加的肺癌死亡率有关.
- 在英国生物银行队列中证实了PRS和肺癌死亡率之间的关联 (p = 0.002).
结论:
- 较高的多基因风险评分是肺癌死亡率的独立预测指标.
- 作为一种生物标志物,PRS证明了其有用性,用于识别患有致命肺癌风险较高的个体.
- 这些发现支持将PRS纳入肺癌查方案的可能性.
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