鉴定具有与侵袭性前列腺癌和生存相关的功能丧失罕见变异的基因
Edward J Saunders1, Tokhir Dadaev1, Mark N Brook1
1Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
European urology oncology
|March 8, 2024
概括
在ATM,BRCA2,MSH2和NBN中的罕见基因突变与侵袭性前列腺癌 (PrCa) 有关. 这些遗传变异与较低的生存率有关,这突显了它们对PrCa风险评估的重要性.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 基因组医学是基因组医学.
背景情况:
- 前列腺癌 (PrCa) 是全世界男性癌症死亡的主要原因.
- 在BRCA2的生殖基因突变是已知的侵略性PrCa的风险因素,但其他基因的作用不太清楚.
研究的目的:
- 使用聚合的罕见变体测序数据,识别与PrCa攻击性相关的基因.
- 为了分析来自英国遗传前列腺癌研究 (UKGPCS) 的六项先前研究的数据.
主要方法:
- 分析了6805例PrCa病例的队列.
- 在所有样本中测序了10个候选基因.
- 检查了罕见的假定功能丧失 (pLOF) 变体,以确定与侵略性PrCa分类的关联.
主要成果:
- 在ATM,BRCA2,MSH2和NBN中的pLOF突变与PrCa攻击性有显著的关联 (OR = 2.6718.9).
- 这些基因与MLH1一起,与特定的二次表型有关.
- 这些生殖系突变的携带者具有显着较短的PrCa特异性生存期 (HR = 2.15).
结论:
- 在ATM,BRCA2,MSH2和NBN中罕见的pLOF变异与侵略性PrCa.的风险增加密切相关.
- 这些发现支持在PrCa查和治疗决策中使用特定的基因组.
- 识别这些突变的男性可以帮助预测PrCa死亡率的风险增加.
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