甲状腺癌病因异质性的遗传驱动因素
Genetic drivers of etiologic heterogeneity in thyroid cancer.
摘要(中文译文)
甲状腺癌是最常见的内分泌恶性肿瘤，但其生物学基础仍未完全阐明。本研究表明，甲状腺癌的常见风险等位基因指向疾病易感性背后不同的生物学通路。我们对甲状腺癌进行了多祖先全基因组关联荟萃分析（16,167例病例和2,430,374例对照），识别出51个独立位点，其中21个为既往未报道的位点。通过将这些位点与151个甲状腺癌相关性状的遗传关联进行整合，我们识别出与甲状腺功能、致癌通路及混合生理功能相关的多效性机制聚类。两个甲状腺特异性聚类分别与促甲状腺激素或甲状腺生长和功能相关，并在甲状腺组织中富集。致癌聚类包括DNA修复基因（ATM、CHEK2、TP53）和端粒维持基因（TERT），提示存在共享的癌症机制。聚类特异性多基因评分在不同祖先群体中与甲状腺疾病、癌症及代谢性状相关，提示甲状腺癌风险存在不同的遗传亚型，并支持基于多效性的遗传风险分层方法。
Abstract
Thyroid cancer is the most common endocrine malignancy, yet its biological underpinnings remain incompletely understood. Here we show that common risk alleles for thyroid cancer point to distinct biological pathways underlying disease susceptibility. We perform a multi-ancestry genome-wide association meta-analysis of thyroid cancer (16,167 cases and 2,430,374 controls), identifying 51 independent loci, including 21 not previously reported. By integrating these loci with genetic associations for 151 thyroid-cancer-related traits, we identify pleiotropic mechanistic clusters linked to thyroid function, oncogenic pathways, and mixed physiological function. Two thyroid-specific clusters, associated with thyroid stimulating hormone or thyroid growth and function, are enriched in thyroid tissues. Oncogenic clusters include DNA repair (ATM, CHEK2, TP53) and telomere maintenance (TERT) genes, implicating shared cancer mechanisms. Cluster-specific polygenic scores are associated with thyroid disease, cancer, and metabolic traits across ancestry groups, suggesting distinct genetic subtypes of thyroid cancer risk and supporting pleiotropy-based approaches to genetic risk stratification.
如何引用
AMA
Yon Ho Jee, Nikita Pozdeyev, Christopher R Gignoux, Samantha White, Bryan R Haugen, Anurag Verma, et al. Genetic drivers of etiologic heterogeneity in thyroid cancer.. Nature communications. 2026; doi:10.1038/s41467-026-75111-8.
APA
Yon Ho Jee, Nikita Pozdeyev, Christopher R Gignoux, Samantha White, Bryan R Haugen, Anurag Verma, et al (2026). Genetic drivers of etiologic heterogeneity in thyroid cancer.. Nature communications. https://doi.org/10.1038/s41467-026-75111-8
GB/T 7714
Yon Ho Jee, Nikita Pozdeyev, Christopher R Gignoux, Samantha White, Bryan R Haugen, Anurag Verma, et al. Genetic drivers of etiologic heterogeneity in thyroid cancer.[J]. Nature communications, 2026 doi:10.1038/s41467-026-75111-8.
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