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调查甲状腺特征与乳腺癌之间的共同遗传风险因素
Elise A Lucotte1, Yazdan Asgari1, Pierre-Emmanuel Sugier1,2
1Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807 Villejuif, France.
这项研究揭示了与乳腺癌 (BC) 和甲状腺疾病相关的共同遗传因素. 较高的甲状腺激素 (FT4) 和较低的甲状腺刺激激素 (TSH) 水平与增加的BC风险有关,表明存在遗传联系.
科学领域:
- 遗传学 遗传学 是一个
- 内分泌学 在内分泌学.
- 在瘤学瘤学.
背景情况:
- 关于乳腺癌 (BC) 与甲状腺疾病之间的关联的观察性研究产生了相互矛盾的结果.
- 研究共享的遗传风险因素为了解这些疾病之间的复杂关系提供了一种替代方法.
研究的目的:
- 识别和描述乳腺癌 (BC) 和各种甲状腺特征之间的共同遗传风险因素.
- 探索影响BC和甲状腺疾病的遗传相关性和类基位.
主要方法:
- 利用遗传相关性分析来评估BC和甲状腺特征之间的关系,如甲状腺素 (FT4) 和甲状腺刺激激素 (TSH) 水平.
- 采用多基因风险评分 (PRS) 来评估甲状腺特征遗传倾向与BC风险的关联.
- 应用了PLACO方法和同源化分析来检测和确认共享的遗传位置及其潜在的因果作用.
主要成果:
- 在BC和FT4水平 (corr=0.13,p=2.0×10−4) 之间发现了显著的阳性遗传相关性,以及与TSH水平 (corr=-0.09,p=0.03) 的负相关性,特别是在雌激素受体阳性BC中.
- 对于FT4和甲状腺功能障碍的PRS与BC风险有积极的关联,而对于TSH的PRS则显示出相反的关联.
- 确定了49个与BC和甲状腺特征相关的位点,包括与TSH水平和BC风险相关的14q32.33和17q21.31的新类位点.
结论:
- 这项研究提供了强有力的证据,表明乳腺癌和甲状腺疾病之间存在共同的遗传风险因素,特别是FT4和TSH水平.
- 这些发现突显了内分泌和瘤疾病之间的复杂相互作用,表明了涉及大脑和免疫系统的潜在生物途径.
- 鉴定出了新的类基位,需要进一步研究它们在BC和甲状腺疾病的病因学中的作用.
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