Department of General Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA.
Ann Surg Oncol. 2021 Oct;28(11):6590-6600. doi: 10.1245/s10434-021-09745-x. Epub 2021 Mar 3.
The prevalence of non-medullary thyroid cancer (NMTC) is increasing worldwide. Although most NMTCs grow slowly, conventional therapies are less effective in advanced tumors. Approximately 5-15% of NMTCs have a significant germline genetic component. Awareness of the NMTC susceptibility genes may lead to earlier diagnosis and better cancer prevention.
The aim of this study was to provide the current panorama of susceptibility genes associated with NMTC and the spectrum of diseases associated with these genes.
Twenty-five candidate genes were identified by searching for relevant studies in PubMed. Each candidate gene was carefully checked using six authoritative genetic resources: ClinGen, National Comprehensive Cancer Network guidelines, Online Mendelian Inheritance in Man, Genetics Home Reference, GeneCards, and Gene-NCBI, and a validated natural language processing (NLP)-based literature review protocol was used to further assess gene-disease associations where there was ambiguity.
Among 25 candidate genes, 10 (APC, DICER1, FOXE1, HABP2, NKX2-1, PRKAR1A, PTEN, SDHB, SDHD, and SRGAP1) were verified among the six genetic resources. Two additional genes, CHEK2 and SEC23B, were verified using the NLP protocol. Seventy-nine diseases were found to be associated with these 12 NMTC susceptibility genes. The following diseases were associated with more than one NMTC susceptibility gene: colorectal cancer, breast cancer, gastric cancer, kidney cancer, gastrointestinal stromal tumor, paraganglioma, pheochromocytoma, and benign skin conditions.
Twelve genes predisposing to NMTC and their associated disease spectra were identified and verified. Clinicians should be aware that patients with certain pathogenic variants may require more aggressive surveillance beyond their thyroid cancer risk.
全球范围内非髓样甲状腺癌（NMTC）的患病率正在上升。虽然大多数 NMTC 生长缓慢，但传统疗法在晚期肿瘤中的效果较差。大约 5-15%的 NMTC 具有显著的种系遗传成分。对 NMTC 易感性基因的认识可能导致更早的诊断和更好的癌症预防。
本研究旨在提供与 NMTC 相关的易感性基因的当前全景图，以及与这些基因相关的疾病谱。
通过在 PubMed 中搜索相关研究，确定了 25 个候选基因。使用六个权威遗传资源：ClinGen、国家综合癌症网络指南、在线孟德尔遗传数据库、遗传学参考数据库、GeneCards 和 Gene-NCBI，仔细检查每个候选基因，并使用经过验证的基于自然语言处理（NLP）的文献综述协议进一步评估存在歧义的基因-疾病关联。
在 25 个候选基因中，有 10 个（APC、DICER1、FOXE1、HABP2、NKX2-1、PRKAR1A、PTEN、SDHB、SDHD 和 SRGAP1）在六个遗传资源中得到了验证。另外两个基因 CHEK2 和 SEC23B 通过 NLP 协议进行了验证。发现 79 种疾病与这 12 个 NMTC 易感性基因相关。以下疾病与多个 NMTC 易感性基因相关：结直肠癌、乳腺癌、胃癌、肾癌、胃肠道间质瘤、副神经节瘤、嗜铬细胞瘤和良性皮肤状况。
确定并验证了 12 个易患 NMTC 的基因及其相关疾病谱。临床医生应该意识到，具有某些致病性变异的患者可能需要超出其甲状腺癌风险的更积极监测。
