title: [Genotype-phenotype correlations in multiple endocrine neoplasia type 2].
abstract: OBJECTIVE
  To evaluate the relationship between different RET mutations and the aggressiveness of hereditary medullary thyroid cancer (HMTC) or the presentation of other endocrine disorders in patients with multiple endocrine neoplasia type 2 (MEN2).
  
  
  METHODS
  A total of 73 thyroid medullary carcinoma patients from 22 Chinese kindreds who were treated in our center from 2010 to 2015 were enrolled. RET genes in the patients and their relatives were screened.
  
  
  RESULTS
  According to the clinical data and 2015 American Thyroid Association (ATA) guidelines, patients were classified into 3 RET mutation risk groups: Modest, 24 cases; High, 48 cases; and Highest, 1 case. Multivariate analysis showed an increased likelihood of MTC stage III or IV at diagnosis with increasing of age and risk. The likelihood increased 11.6% per year of age at surgery (95% confidence interval, 1.040-1.198; P=0.002). The likelihood in patients with high risk was 7.9 times higher than patients with modest risk (95% confidence interval, 1.607-38.717; P=0.003). Aside from one patient with MEN2B, other 72 patients were MEN2A, of them, 28 cases from 7 kindreds with classical MEN2A (codon 634 & 618), 14 cases from 3 kindreds with cutaneous lichen amyloidosis (codon 634), 4 cases from 1 kindred with Hirschsprung's disease (codon 620), and 26 cases from 10 kindreds with familial MTC.
  
  
  CONCLUSIONS
  The aggressiveness of HMTC and the presentation of other endocrine diseases are related to specific RET mutations. For RET mutation carriers, MTC and other endocrine diseases should be diagnosed and treated early based on the RET genotypes.
authors.affiliation: Department of Head and Neck Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: X W
authors.initials: XW
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Head and Neck Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Y B
authors.initials: YB
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology, Renji Hospistal, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: H F
authors.initials: HF
authors.lastname: Wan
authors.affiliation: Department of Head and Neck Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: B
authors.initials: B
authors.lastname: Zhang
authors.forename: D G
authors.initials: DG
authors.lastname: Yan
authors.affiliation: Department of Head and Neck Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: W S
authors.initials: WS
authors.lastname: Liu
authors.affiliation: Department of Head and Neck Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Z G
authors.initials: ZG
authors.lastname: Xu
authors.affiliation: Department of Head and Neck Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: P Z
authors.initials: PZ
authors.lastname: Tang
mesh_terms: D044466:Asian People; D018276:Carcinoma, Medullary / Q000151:congenital* / Q000235:genetics; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D018813:Multiple Endocrine Neoplasia Type 2a / Q000145:classification / Q000150:complications / Q000235:genetics*; D018814:Multiple Endocrine Neoplasia Type 2b / Q000235:genetics; D015999:Multivariate Analysis; D009154:Mutation; D010641:Phenotype; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D051096:Proto-Oncogene Proteins c-ret