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Joon Ho Kang1, Youngkee Lee1, Dong Jun Kim1
1R&D division Genoplan Korea Inc, Seoul, 06611, Republic of Korea.
整合常见和罕见的遗传变异可以改善癌症风险预测. 扩展多基因风险评分 (PRS) 方法增强了分层,识别了具有显著更高乳腺癌和前列腺癌风险的个体.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 生物信息学是一种生物信息学.
背景情况:
- 多基因风险评分 (PRS) 和罕见变异查是癌症风险预测的关键.
- 准确的癌症风险评估需要整合常见和罕见的遗传变异.
- 将罕见变异影响与PRS用于风险分层的结合提出了挑战.
研究的目的:
- 为增强癌症风险分层制定一个系统模型.
- 整合多基因和单基因风险因素,以改善预测.
- 分析常见和罕见变体对乳腺癌和前列腺癌风险的综合影响.
主要方法:
- 英国生物银行对外体序列和阵列数据 (454,711和487,409个样本) 的分析.
- 开发一种扩展的多基因风险评分 (EPRS) 方法.
- 具有癌症特异性罕见变异的基因的优先级和聚类,使用几率比率和可归因于人口的分数.
主要成果:
- 采用EPRS方法,为乳腺癌和前列腺癌提供了更有效的风险分层.
- 患有高PRS和罕见高影响变异的个体患癌症的风险增加了15倍 (乳腺) 和22倍 (前列腺).
- 综合风险概况表明,在同一PRS组内的不同罕见变异群体中存在差异性.
结论:
- EPRS方法显著提高了乳腺癌和前列腺癌的风险分层.
- 整合常见和罕见的遗传变异为个性化癌症风险评估提供了宝贵的见解.
- 这种方法有可能应用于其他癌症类型和未来的研究.
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