在不育的男性中,遗传性癌症相关的生殖系变异的负载显著增加
Anu Valkna1, Anna-Grete Juchnewitsch1, Lisanna Põlluaas1
1Chair of Human Genetics, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
Human reproduction open
|March 10, 2025
概括
与肥沃男性相比,不孕男性在遗传性癌症基因中携带致病变体的风险增加了近五倍. 这一发现表明男性不育和癌症的共同遗传原因,使不育个体能够更早地进行癌症查.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
- 生殖医学 生殖医学
背景情况:
- 精子数量低的男性患癌症的风险增加2倍.
- 患有单一性不孕症的男性患癌症的患病率增加了4倍.
- 建议男性不孕症和癌症之间有共同的分子病因.
研究的目的:
- 确定与生育男性相比,不育男性遗传性癌症相关的生殖系变异的流行率和概况.
- 研究男性不孕症和癌症倾向的潜在共同遗传基础.
主要方法:
- 对157个遗传性癌症基因中的生殖线可能致病和致病 (LP/P) 变异的回顾性分析.
- 研究队列包括来自爱沙尼亚雄性病学 (ESTAND) 队列的522名不育和323名肥沃男性.
- 外体测序数据经过自动过,手动病原性评估和桑格测序确认.
主要成果:
- 与生育男性相比 (1.5%;P = 2.3 × 10−4),不孕男性的LP/P发现量 (6.9%) 几乎高出5倍.
- 研究结果涵盖了24个遗传性癌症基因,其中Fanconi贫血路径基因 (例如BRCA2,FANCM) 经常受到影响.
- 六名患有遗传性癌症变异的男性被诊断出患有瘤;家族史显示10例病例的亲属患有癌症.
结论:
- 遗传性癌症基因中引起疾病的变异在不育男性中存在显著的丰富.
- 共同的遗传病因可能会导致男性不孕症和遗传性癌症.
- 将遗传性癌症基因分析整合到男性不孕症工作中,可以提供早期癌症检测和管理的好处.
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