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墨西哥标签协作交叉:宿主遗传学影响了与石棉有关的疾病延迟,但一旦瘤发展,几乎没有影响
Scott A Fisher1,2,3, Kimberley Patrick1,2,3, Tracy Hoang1,3
1National Centre for Asbestos Related Diseases (NCARD), Perth, WA, Australia.
Frontiers in toxicology
|May 2, 2024
概括
主体遗传学会影响与石棉有关的疾病 (ARD) 的易感性和潜伏性,但一旦建立了间皮瘤,不会影响病变的进展. 这项研究确定了关键基因及其人类正义基因,为石棉诱导的癌症提供了潜在的治疗点.
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
- 毒理学 毒理学 毒理学
背景情况:
- 众所周知,遗传因素会影响对与石棉有关的疾病 (ARD) 的易感性,包括间皮瘤.
- 然而,特定的宿主修饰基因及其在疾病发展中的作用仍然在很大程度上未被确定.
研究的目的:
- 使用协作十字 (CC) 鼠标资源和MexTAg中皮瘤鼠标模型的组合,识别与中皮瘤易感性相关的基因.
- 评估宿主基因对ARD发育,潜伏和进展的影响.
主要方法:
- 交叉了72个基因不同的CC小鼠菌株与MexTAg小鼠,以创建CC-MexTAg (CCMT) 后代.
- 暴露于石棉的CCMT后代和监测的存活率,疾病发病 (潜伏),疾病进展和炎体积.
- 识别了特定于表型的修饰基因,并使用间皮瘤数据集验证了人类的正义基因.
主要成果:
- 在72个基因不同的CCMT菌株中观察到总生存率和疾病延迟率的显著变化.
- 宿主遗传因素影响了疾病的潜伏时间,但在美索瘤建立后对疾病进展起到了有限的作用.
- 6,12和X染色体上的定量特征位置 (QTL) 与ARD存活/延迟有关,八个候选基因在小鼠和人类数据集中都显示出显著的影响.
结论:
- 宿主遗传因素在与石棉有关的疾病易感性和潜伏性中起着至关重要的作用.
- 一旦建立了间皮瘤,遗传变异不会显著影响疾病的进展.
- 鉴定候选修饰基因及其人类同类物,为在石棉诱导的致癌过程中新的治疗点提供了潜在的途径.
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