实施乳腺癌家族风险分层和临床管理,使用多基因风险评分评估:试点研究
Barbara Rizzacasa1, Vanessa Nicolì1, Chantal Tancredi1
1Department of Biomedicine and Prevention, University of Rome "Tor Vergata", 00133 Rome, Italy.
Journal of personalized medicine
|October 25, 2024
概括
多基因风险评分 (PRS) 有助于对家庭的乳腺癌 (BC) 风险进行分层. PRS改善了对非携带高风险基因的人的风险评估,并补充了中等风险家庭的变异状态.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 在瘤学瘤学.
- 个性化医疗是个性化的医疗.
背景情况:
- 准确识别乳腺癌 (BC) 风险较高的妇女对于量身定制查方案至关重要.
- 遗传因素,包括易感基因中的致病性/可能致病性变体 (PVs/LPVs) 和多基因背景 (多基因风险评分,PRS),有助于BC风险.
- 在已知遗传倾向的家庭中,PRS可能会改变BC风险.
研究的目的:
- 评估PRS在高风险和中等风险家庭中评估乳腺癌 (BC) 风险的实用性.
- 确定PRS如何影响已知BC易感变异的携带者和非携带者的风险分层.
主要方法:
- 追溯试点研究涉及来自高风险 (BRCA1/BRCA2) 和中等风险 (PALB2,ATM) 乳腺癌家庭的妇女.
- 来自577,113个BC相关变异的多基因风险评分 (PRS) 的评估.
- 使用BOADICEA模型计算调整的终身BC风险,考虑PV/LPV的载体状态和PRS.
主要成果:
- 在BRCA1/BRCA2载体中,PV/LPV是主要的风险分层,而PRS增强了非载体的风险估计.
- 对于PALB2和ATM家族,PRS和PV/LPV载体身份的组合提供了更全面的终身风险评估.
- PRS在量化遗传家族背景以改善个体风险分层方面表现出价值.
结论:
- 多基因风险评分 (PRS) 可以量化乳腺癌 (BC) 风险的遗传家族成分.
- 将PRS与变异载体状态相结合,可以改善BC家族中的个体风险分层.
- 这些发现支持在BC家庭女性个性化临床管理策略中使用PRS.
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