致病性或可能致病性生殖系变异的流行率和风景及其与非选择性中国妇科癌症患者体外表型的关联
Hao Wen1,2, Qin Xu3, Xiujie Sheng4
1Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
JAMA network open
|July 31, 2023
概括
生殖系致病或可能致病 (P/LP) 变种在患有妇科癌症的中国妇女中普遍存在,特别是卵巢和子宫内膜类型. 这些变异,通常是可行的,突显了基因测试对于改善风险评估和治疗的重要性.
科学领域:
- 妇科瘤学 妇科瘤学
- 癌症基因组学 癌症基因组学
- 遗传性癌症综合征 遗传性癌症综合征
背景情况:
- 了解生殖系和体质遗传改变对于妇科癌症的风险分层和治疗策略至关重要.
- 生殖线变异可以使个体易患妇科恶性瘤,影响癌症风险和患者的结果.
研究的目的:
- 确定生殖线致病或可能致病 (P/LP) 变体在未经选择的患有妇科癌症的中国患者中的患病率和谱.
- 调查生殖系P/LP变体与体质瘤形状之间的关联,以及癌症发病时的年龄等癌症风险因素.
主要方法:
- 一项涉及回顾性招生1610名被诊断患有卵巢,子宫内膜或子宫癌的中国妇女的横截面研究.
- 使用520个基因组进行了瘤正常测序,随后进行了统计分析,以评估变异率和与临床和体质数据的关联.
主要成果:
- 生殖线P/LP变异的患病率在卵巢癌中为20.5%,子宫内膜癌中为13.4%,子宫癌中为6.4%.
- 很大一部分 (95.1%) 的生殖系发现是潜在的可操作的,主要涉及同源重组修复 (HRR) 和不匹配修复基因.
- 与白人人口相比,患有子宫内膜癌的中国患者的P/LP变异率较高. 发病时年龄较小与不匹配修复 (卵巢,子宫内膜) 和HRR (子宫) 基因中的P/LP变异有关.
结论:
- 这项研究揭示了患有妇科癌症的中国女性生殖系P/LP变异的风景,强调了显著的遗传成分.
- 这些发现强调了使用大型基因面板用于妇科癌症的生殖系遗传测试的重要性,特别是用于识别可操作的突变和理解遗传风险.
- 该研究强调了以前低估的对子宫癌的遗传性贡献,并建议改进基因检测策略.
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