高风险的致病性生殖系变异在血缘亲属的BRCA1/2阴性试验者
Reiko Yoshida1,2, Tomoko Kaneyasu3, Arisa Ueki4
1Division of Cancer Genomics, Cancer Institute, Japanese Foundation for Cancer Research (JFCR), 3-8-31 Ariake, Koto-ku, Tokyo, Japan.
Breast cancer (Tokyo, Japan)
|July 13, 2024
概括
致病性生殖系变体 (PGVs) 在遗传癌症基因负的个体的血亲 (BRs) 中被发现. 需要一个新的测试策略来补充这些处于风险的亲属的现有级联测试.
科学领域:
- 遗传学 遗传学 是一个
- 在瘤学瘤学.
- 预防医学 预防医学
背景情况:
- 鉴定致病性生殖系变异 (PGVs) 对于在高危血亲 (BRs) 中量身定制的预防性癌症护理至关重要.
- 级联测试是已知遗传癌症基因突变 (PGV阳性探针) 个体的亲属的标准.
- 没有发现突变的个体的亲属 (PGV阴性试验者) 中PGV的患病率不太清楚.
研究的目的:
- 调查遗传性乳腺癌和卵巢癌 (HBOC) 基因突变阴性测试的试验者的血亲 (BRs) 中致病性生殖系变异 (PGVs) 的流行情况.
- 为了确定PGV是否存在于亲属中,即使试验物不携带已知的突变.
- 为改善遗传性癌症综合征遗传性癌症测试策略的开发提供信息.
主要方法:
- 评估了281名实验对象中的682名血亲 (BRs) 的PGV患病率.
- 专注于BRCA1/BRCA2野生型遗传性乳腺和卵巢癌 (HBOC) 综合征的试验者.
- 在PGV阳性与PGV阴性试验者的BR中比较了PGV发现.
主要成果:
- 在45.8%的PGV阳性试验对象的亲属和2.2%的PGV阴性试验对象的亲属中发现了致病性生殖系变异 (PGVs).
- 11个高风险的PGV (BRCA1,BRCA2,TP53) 仅在血亲中发现,而不是在试验者中.
- 与非癌症东亚人口相比,亲属中PGV的患病率明显高.
结论:
- 这项研究强调了在血缘亲属中存在病原性生殖系变异 (PGVs),即使试验样本是负的.
- 研究结果表明,目前的级联测试可能会错过某些家庭早期检测的机会.
- 建议采用一种新的基因测试方案,以补充现有的级联测试协议,以全面评估癌症风险.
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