基因组测定与CHEK2相关的癌症倾向
Sun Young Kim1,2, Jung Kim1, Mark Ramos1
1Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.
medRxiv : the preprint server for health sciences
|October 7, 2024
概括
生殖系CHEK2变种增加了多种癌症的风险,包括乳腺癌,男性生殖器癌和尿道癌. 患有CHEK2致病变体的个体在较年轻时就会患上癌症,这凸显了对量身定制的监测策略的需要.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 癌症研究 癌症研究
- 流行病学 流行病学
背景情况:
- 已知CHEK2基因中的有害生殖系变异会增加乳腺癌和前列腺癌的风险.
- 关于CHEK2变异与其他癌症相关的证据有限或相互矛盾.
- 基因组鉴定是量化特定基因变异个体癌症风险的强大工具.
研究的目的:
- 要量化癌症风险,患病率和存活结果,在个体与生殖线CHEK2致病性/可能致病性 (P/LP) 变体 (异胞体).
- 通过使用人口规模数据,调查CHEK2 P/LP变体与广泛的癌症类型之间的关联.
- 为了比较CHEK2异构和对照之间的癌症透率和存活率.
主要方法:
- 在两个大型的外体序列生物库 (英国生物库和盖辛格MyCode) 中发现了生殖系CHEK2变异,这些生物库与电子健康记录相关联.
- 变种根据ACMG/AMP标准进行分类,异构卵携带P/LP变种,对照具有良性或野生型CHEK2.
- 使用SAIGE-GENE+进行关联分析,以调整相关性,并应用Bonferroni校正.
主要成果:
- CHEK2异构体对所有测试癌症的风险显著增加,包括乳腺癌 (OR=1.54-1.84),男性生殖器癌 (OR=1.61-1.77),尿路癌 (OR=1.56-1.75),淋巴细胞/血液形成癌 (OR=1.42-2.11).
- 癌症透率在CHEK2异构成体中明显较年轻,与两组对照组相比.
- 在英国生物银行CHEK2异构成体中,总体存活率显著下降,但在MyCode队列中没有.
结论:
- 在人口规模队列中的基因组鉴定证实,CHEK2异性与多种癌症类型的风险增加有关.
- CHEK2异构体的癌症发病时间较早,因此需要制定有针对性的监测和管理策略.
- 需要进一步的研究来完善风险预测,并优化携带CHEK2病原体变异的个体的临床管理.
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