在单个和多个癌症诊断中确定的癌症倾向基因
Jeffrey W Shevach1, Jianfeng Xu2, Nathan Snyder1
1Department of Medicine and the Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina.
JAMA oncology
|August 28, 2025
概括
在一项大型人群研究中,16个癌症倾向基因中的罕见致病变体 (RPV) 与单一和多重癌症诊断的几率增加有关. 多基因小组测试可能对这些变异的个体有益.
科学领域:
- 遗传学
- 癌症学
- 人口健康
背景情况:
- 了解罕见致病变体 (RPV) 的癌症风险通常依赖于家庭或临床研究,这可能容易产生偏见.
- 基于人群的研究对于对癌症风险的基因关联进行公正评估至关重要.
研究的目的:
- 量化已知癌症倾向基因中的RPV与单个和多个癌症诊断的风险之间的联系.
- 在一个大规模的,未经选择的,基于人口的队列中调查这些关联.
主要方法:
- 分析了183,627名英国生物库参与者 (仅限白人) 的全外体序列数据.
- 通过强大的最佳序列内核关联测试和Firth逻辑回归来评估96个癌症倾向基因的遗传变异.
- 通过医院,癌症登记和死亡登记数据来确定癌症诊断.
主要成果:
- 在16个基因 (包括ATM,BRCA1,BRCA2,CHEK2,TP53) 中的RPV与至少一个癌症诊断有显著关联.
- RPV与任何癌症 (OR,1. 87) 和多种原发性癌症 (OR,2. 56) 的几率增加有关.
- 这些基因中的RPV载体频率为任何癌症的6. 28%,多种癌症的8. 36%.
结论:
- 这项研究证实了基因与癌症的相关性.
- 癌症倾向基因中的RPV与多种原发性癌症的风险增加有关.
- 研究结果表明,对于这些基因中发现RPV的个体,多基因组测试可能是合理的.
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