癌症中的多位基遗传性瘤等位基综合征:对临床实践的含义
Jeanette Yuen1, Siqin Zhou2, Rebecca Caeser1,3
1Cancer Genetics Service, Division of Medical Oncology, National Cancer Centre, Singapore, Singapore.
European journal of human genetics : EJHG
|January 22, 2025
概括
多位遗传性瘤等位基因综合征 (MINAS) 携带者面临更早,更频繁的癌症风险的增加. 管理策略应考虑这些双载体中病原体变异的支配性或衰退性.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 临床遗传学 临床遗传学
背景情况:
- 多基因测试增加了在癌症倾向基因中具有多种致病变异 (PV) 的家族的识别,称为MINAS.
- 由于对其临床影响的理解有限,MINAS携带者面临非最佳癌症管理的风险.
- 现有的文献缺乏对MINAS载体与癌症严重程度和呈现相关性的全面分析.
研究的目的:
- 系统地审查在癌症倾向基因中发表的MINAS病例.
- 调查MINAS与更严重的癌症呈现之间的关联,包括发病频率和年龄.
- 探索PV主导性或衰退性对MINAS载体临床特征的影响.
主要方法:
- 对公布的MINAS案件进行系统审查.
- 对413名MINAS携带者进行分析,其中包括来自新加坡国家癌症中心的33例新病例.
- 统计测试用于评估载体特征,PV数量和临床结果之间的关联.
主要成果:
- 与单单基 (21.5%) 和非载体 (10.3%) 相比,MINAS载体的恶性瘤发病率 (31.7%) 显著更高 (p<0.001).
- 携带MINAS的患者的初次癌症诊断年龄中位数较小 (40.0岁),癌症发病时间较早 (24.9%) (p<0.001).
- 主导主导的 (D-D) PV载体报告的多重恶性瘤 (34.0%) 比主导衰退的 (D-R) (23.9%) 和衰退衰退的 (R-R) (20%) 载体 (p=0.051) 更多.
结论:
- 携带MINAS的患者有更高的发病率和更早的恶性瘤发病倾向.
- 双载体中PV的遗传模式 (主导或衰退) 影响临床表现.
- 为MINAS患者提出了一个管理框架,考虑双载体PV的性质.
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