文章：

丹麦1930–2021年间多发性内分泌腺瘤病2A型RET C611Y种系变异：一项全国性研究

RETC611Y Germline Variant in Multiple Endocrine Neoplasia Type 2A in Denmark 1930–2021: A Nationwide Study

原文发布日期：23 January 2025

DOI: 10.3390/cancers17030374

类型: Article

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英文摘要：

Background: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare hereditary cancer syndrome caused by pathogenic variants in the rearranged during transfection (RET) gene and is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), primary hyperparathyroidism (PHPT), cutaneous lichen amyloidosis (CLA), and Hirschsprung’s disease. Phenotypic data on theRETC611Y variant remain sparse. Consequently, we aimed to establish a clinical risk profile.Methods: We conducted a nationwide study of all cases (n = 128) born after 1 January 1930 and recognized as carrying theRETC611Y variant in Denmark before 1 April 2021.Results: The median follow-up after birth was 47 years (range, 3–92). Age-related penetrance at age 70 years for MTC was 98% (CI, 91–100), for PHEO 24% (CI, 16–37), and for PHPT 10% (CI, 5–20). None had CLA or Hirschsprung’s disease. The age-related progression of MTC was significant (p< 0.001). The mean age at T0N0M0 was 16 years (CI, 12–20), at T1-4N0M0 38 years (CI, 34–42), at TxN1M0 45 years (CI, 38–53) and at TxNxM1 49 years (CI, 36–61). At the last follow-up, 56% of thyroidectomized cases (n = 103) were biochemically cured. Overall survival at 70 years was 74% (CI, 59–84).Conclusions:RETC611Y is associated with a very high penetrance of MTC and a low penetrance of PHEO and PHPT. CLA and Hirschsprung’s disease almost never occur. MTC seems moderately aggressive, but large variability can be seen. Overall survival may be comparable to that of the general population.

摘要翻译： 

背景：2A型多发性内分泌腺瘤病（MEN 2A）是一种罕见的遗传性癌症综合征，由转染重排（RET）基因的致病性变异引起，其特征包括甲状腺髓样癌（MTC）、嗜铬细胞瘤（PHEO）、原发性甲状旁腺功能亢进症（PHPT）、皮肤苔藓样淀粉样变性（CLA）以及先天性巨结肠症。目前关于RET C611Y变异的表型数据仍然有限。因此，本研究旨在建立其临床风险特征。 方法：我们在全国范围内对1930年1月1日后出生、且在2021年4月1日前于丹麦被确认携带RET C611Y变异的所有病例（n = 128）进行了研究。 结果：出生后的中位随访时间为47年（范围：3-92年）。70岁时MTC的年龄相关外显率为98%（置信区间CI，91-100），PHEO为24%（CI，16-37），PHPT为10%（CI，5-20）。未发现CLA或先天性巨结肠症病例。MTC的年龄相关进展具有显著性（p < 0.001）。达到T0N0M0期的平均年龄为16岁（CI，12-20），T1-4N0M0期为38岁（CI，34-42），TxN1M0期为45岁（CI，38-53），TxNxM1期为49岁（CI，36-61）。在末次随访时，接受甲状腺切除术的病例（n = 103）中有56%实现了生化治愈。70岁时的总生存率为74%（CI，59-84）。 结论：RET C611Y变异与MTC的极高外显率以及PHEO和PHPT的低外显率相关。CLA和先天性巨结肠症几乎不发生。MTC似乎具有中等侵袭性，但存在较大变异性。总生存率可能与普通人群相当。

原文链接：

RETC611Y Germline Variant in Multiple Endocrine Neoplasia Type 2A in Denmark 1930–2021: A Nationwide Study