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通过基因吸烟相互作用影响食道状细胞癌的HORMAD1多态性

Xinying Yue¹, Zifei Yang¹, Jialing Ma¹

¹Department of Health Toxicology, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Molecular carcinogenesis

|August 28, 2025

概括

吸烟会增加食道癌症的风险, 但基因相互作用很重要. HORMAD1基因变异通过改变DNA修复来保护吸烟者,从而有可能预测风险.

科学领域:

遗传学和基因组学
癌症生物学
分子流行病学

背景情况:

烟草烟雾是食道状细胞癌 (ESCC) 的主要危险因素.
吸烟者对ESCC的个人易感性有所不同,这表明基因与环境的相互作用.
了解这些相互作用对于识别高风险个体至关重要.

研究的目的:

确定参与ESCC致癌的烟雾反应基因.
研究HORMAD1在DNA修复中的作用及其与吸烟者的ESCC风险的关联.
探索HORMAD1变体在基因吸烟相互作用中的功能机制.

主要方法:

吸烟者和非吸烟者的正常和瘤组织的综合转录基因分析.
在暴露于烟雾成分时评估HORMAD1表达和DNA修复通路激活 (NHEJ和HR) 的体外研究.
一个大规模的,两阶段的病例控制研究,以确定与ESCC风险相关的HORMAD1遗传变异.
功能性测试以阐明已识别的变体通过染色体相互作用对基因调节的影响.

主要成果:

包括HORMAD1在内的四个对烟雾敏感的基因被确定为ESCC的潜在贡献者.
在ESCC细胞中的HORMAD1上调与非同类末端结合 (NHEJ) 的增强和吸烟者的基因组不稳定性相关.
两种HORMAD1变体 (rs11204679和rs33924488) 显示出显著的基因吸烟相互作用,在吸烟者中提供了对ESCC的保护.
这些变体通过改变转录因子结合的远端增强剂来抑制HORMAD1的表达.

结论:

在ESCC中,HORMAD1在烟草烟雾引起的DNA修复失调中发挥着关键作用.
特定的HORMAD1变体可以通过对DNA修复机制的保护作用来调节吸烟者的ESCC风险.
HORMAD1及其变体是ESCC风险分层和精确预防策略的潜在生物标志物.

关键词:

霍马德1 消化管皮细胞癌 (ESCC)基因吸烟的相互作用吸烟反应的基因

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