NTHL1是一种衰退性癌症易感基因
Anna K Nurmi1, Liisa M Pelttari1, Johanna I Kiiski1
1Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Biomedicum Helsinki, P.O. Box 700, 00290, Helsinki, Finland.
Scientific reports
|November 30, 2023
概括
研究人员在NTHL1基因中发现了一种显著的乳腺癌 (BC) 风险变异. 同性卵性携带NTHL1 c.244C>T的携带者面临着大幅增加的BC风险,这表明NTHL1是一种多瘤易感基因.
科学领域:
- 遗传学 遗传学 是一个
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 识别新型乳腺癌 (BC) 风险变体对于了解疾病病因和改善预防策略至关重要.
- 之前的研究表明了潜在的BC倾向基因,但需要在不同人群中进一步验证.
研究的目的:
- 识别与乳腺癌 (BC) 风险相关的新型遗传变异.
- 为了验证之前建议的BC倾向变体,特别是SERPINA3 c.918-1G>C.
- 研究DNA修复基因在BC易感性中的作用.
主要方法:
- 芬兰BC患者的全外体测序和变异分析.
- 41个罕见候选变异的基因定型在38个基因中,跨越大型BC患者和对照队伍.
- 使用FinnGen数据集 (18,786名BC患者,182,927名对照) 评估候选基因中的编码变异.
主要成果:
- 对于SERPINA3或其他最初评估的变体,在初级BC系列中没有发现显著的BC风险关联.
- 在FinnGen数据中,NTHL1 c.244C>T p.(Gln82Ter) 变种显示出与BC的显著关联.
- 同卵性NTHL1c.244C>T载体的BC风险非常高 (OR=44.7),而异卵性载体的BC风险略有增加 (OR=1.39).
- 同性卵性NTHL1变异携带者也表现出结直肠,泌尿道和基底细胞皮肤癌的风险增加.
结论:
- NTHL1 c.244C>T p.(Gln82Ter) 是一种新的BC风险变体,作为一种衰退性易感性因素.
- NTHL1作为一个衰退的多瘤易感基因,影响了几种癌症的风险.
- 在本研究中,SERPINA3 c.918-1G>C变异与BC风险无关.
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