title: The influence of gender, age, and RET polymorphisms on C-cell hyperplasia and medullary thyroid carcinoma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Austrian Research Centers-ARC, Seibersdorf, Austria. andreas.weinhaeusel@arcs.ac.at
authors.forename: Andreas
authors.initials: A
authors.lastname: Weinhaeusel
authors.forename: Christian
authors.initials: C
authors.lastname: Scheuba
authors.forename: Martin
authors.initials: M
authors.lastname: Lauss
authors.forename: Albert
authors.initials: A
authors.lastname: Kriegner
authors.forename: Klaus
authors.initials: K
authors.lastname: Kaserer
authors.forename: Klemens
authors.initials: K
authors.lastname: Vierlinger
authors.forename: Oskar A
authors.initials: OA
authors.lastname: Haas
authors.forename: Bruno
authors.initials: B
authors.lastname: Niederle
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D002116:Calcitonin / Q000097:blood; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012737:Sex Factors; D013961:Thyroid Gland / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D013965:Thyroidectomy
chemical_list: D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret