对23种癌症的病例对照研究与CHEK2的功能分析:东亚风险估计和临床建议
Yuri Takehara1,2, Yoshiaki Usui1, Lenka Stolařová3
1Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
JCO precision oncology
|September 2, 2025
概括
在东亚人群中,CHEK2基因的生殖系损害变异会增加女性患乳腺癌和前列腺癌的风险. 建议对该地区的CHEK2变体携带者进行标准癌症查.
科学领域:
- 遗传学
- 癌症学
- 人口健康
背景情况:
- CHEK2是一种已知的乳腺癌易感基因.
- 对CHEK2在其他癌症中的作用及其在东亚的临床相关性的证据有限.
研究的目的:
- 在东亚人群中研究CHEK2生殖系破坏性变体 (gDV) 的临床相关性.
- 评估CHEK2 gDV与23种癌症风险的相关性.
主要方法:
- 在111,571名东亚人中对CHEK2进行了向测序和功能分析.
- 基于ClinVar,预测和功能数据的生殖系破坏性变体 (gDV) 的定义.
- 对CHEK2 gDV与癌症风险的关联分析,以及临床特征的比较.
主要成果:
- 确定了77种CHEK2 gDV,其中包括36种功能受损的误解变体.
- CHEK2 gDV与女性乳腺癌 (OR=1. 8) 和前列腺癌 (OR=1. 8) 有关.
- 携带者和非携带者之间没有临床特征或预后差异;与东亚其他高发病率的癌症没有关联.
结论:
- 在东亚女性中,CHEK2 gDV与乳腺癌和前列腺癌的风险增加有关.
- 需要仔细考虑CHEK2 gDV携带者的系统临床治疗.
- 建议对东亚的CHEK2 gDV携带者进行标准癌症查,等待其他倾向性指标.
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