Weinhaeusel Andreas, Scheuba Christian, Lauss Martin, Kriegner Albert, Kaserer Klaus, Vierlinger Klemens, Haas Oskar A, Niederle Bruno
Austrian Research Centers-ARC, Seibersdorf, Austria.
Thyroid. 2008 Dec;18(12):1269-76. doi: 10.1089/thy.2008.0139.
RET germline mutations predispose to the development of hereditary medullary thyroid carcinoma (hMTC). Several single nucleotide polymorphisms (SNPs) are described associated with sporadic MTC (sMTC). However, the findings regarding their influence on the clinical course and biological behavior of this disorder are discordant. To clarify the contradictory findings, we studied the association of certain SNPs considering age, gender, and histopathology in a large Austrian cohort with C-cell hyperplasia (CCH) and MTC.
Genotyping of SNPs located in RET codons 691, 769, 836, and 904 from 199 patients with MTC and CCH (basal calcitonin > 10 pg/mL, pentagastrin stimulated > 100 pg/mL) was performed, and the results were analyzed considering gender, age at diagnosis, and histopathology.
No significant difference of SNP frequencies was found in the study patients versus normal controls. In sMTC and sporadic CCH (sCCH) no significant association of SNP frequency with the age at diagnosis was found. In patients with sporadic C-cell disease (sCCH and sMTC), 3.7 times more males than females suffered synchronously from papillary or follicular thyroid cancer (20/97 [20.6%] males; 3/54 [5.6%] females; p = 0.02). sCCH was revealed more frequently in males (89/97, 91.7%) than in females (27/54, 50%; p = 10(-8)). In contrast to males, the ratio of CCH to total C-cell disease was significantly higher in females with hereditary (26/32, 81%) compared to those with sporadic disease (27/54, 50%; p = 0.006).
In this study RET SNPs had no clinical impact on the development of sporadic C-cell disease when the age of diagnosis or gender is considered. C-cell disease seems to predispose males to the development of papillary and follicular thyroid cancer. In addition, at least in females with CCH RET germline mutation, screening is recommended even if the family history is negative for MTC.
RET基因种系突变易导致遗传性甲状腺髓样癌（hMTC）的发生。已有多项单核苷酸多态性（SNP）被描述与散发性甲状腺髓样癌（sMTC）相关。然而，关于它们对该疾病临床进程和生物学行为影响的研究结果并不一致。为了阐明这些相互矛盾的发现，我们在一个包含C细胞增生（CCH）和MTC的大型奥地利队列中，研究了某些SNP与年龄、性别及组织病理学之间的关联。
对199例MTC和CCH患者（基础降钙素>10 pg/mL，五肽胃泌素刺激后>100 pg/mL）进行位于RET密码子691、769、836和904处的SNP基因分型，并根据性别、诊断时年龄和组织病理学分析结果。
研究患者与正常对照之间未发现SNP频率有显著差异。在sMTC和散发性CCH（sCCH）中，未发现SNP频率与诊断时年龄有显著关联。在散发性C细胞疾病（sCCH和sMTC）患者中，男性同时患乳头状或滤泡状甲状腺癌的人数是女性的3.7倍（男性20/97 [20.6%]；女性3/54 [5.6%]；p = 0.02）。sCCH在男性中出现的频率（89/97，91.
