title: Polymorphisms of cell cycle control genes influence the development of sporadic medullary thyroid carcinoma.
abstract: BACKGROUND
  The role of key cell cycle regulation genes such as, CDKN1B, CDKN2A, CDKN2B, and CDKN2C in sporadic medullary thyroid carcinoma (s-MTC) is still largely unknown.
  
  
  METHODS
  In order to evaluate the influence of inherited polymorphisms of these genes on the pathogenesis of s-MTC, we used TaqMan SNP genotyping to examine 45 s-MTC patients carefully matched with 98 controls.
  
  
  RESULTS
  A multivariate logistic regression analysis demonstrated that CDKN1B and CDKN2A genes were related to s-MTC susceptibility. The rs2066827*GT+GG CDKN1B genotype was more frequent in s-MTC patients (62.22%) than in controls (40.21%), increasing the susceptibility to s-MTC (OR=2.47; 95% CI=1.048-5.833; P=0.038). By contrast, the rs11515*CG+GG of CDKN2A gene was more frequent in the controls (32.65%) than in patients (15.56%), reducing the risk for s-MTC (OR=0.174; 95% CI=0.048-0.627; P=0.0075). A stepwise regression analysis indicated that two genotypes together could explain 11% of the total s-MTC risk. In addition, a relationship was found between disease progression and the presence of alterations in the CDKN1A (rs1801270), CDKN2C (rs12885), and CDKN2B (rs1063192) genes. WT rs1801270 CDKN1A patients presented extrathyroidal tumor extension more frequently (92%) than polymorphic CDKN1A rs1801270 patients (50%; P=0.0376). Patients with the WT CDKN2C gene (rs12885) presented larger tumors (2.9±1.8 cm) than polymorphic patients (1.5±0.7 cm; P=0.0324). On the other hand, patients with the polymorphic CDKN2B gene (rs1063192) presented distant metastases (36.3%; P=0.0261).
  
  
  CONCLUSIONS
  In summary, we demonstrated that CDKN1B and CDKN2A genes are associated with susceptibility, whereas the inherited genetic profile of CDKN1A, CDKN2B, and CDKN2C is associated with aggressive features of tumors. This study suggests that profiling cell cycle genes may help define the risk and characterize s-MTC aggressiveness.
authors.affiliation: University of Campinas (FCM - Unicamp)126, Tessalia Vieira de Camargo, Street. Cidade Universitaria Zeferino Vaz, Campinas - São Paulo, 13083-887 BrazilFederal University of Sao Paulo (Unifesp)669, Pedro Toledo Street, São Paulo-SP 04039-032, Brazil.
authors.forename: R B
authors.initials: RB
authors.lastname: Barbieri
authors.affiliation: University of Campinas (FCM - Unicamp)126, Tessalia Vieira de Camargo, Street. Cidade Universitaria Zeferino Vaz, Campinas - São Paulo, 13083-887 BrazilFederal University of Sao Paulo (Unifesp)669, Pedro Toledo Street, São Paulo-SP 04039-032, Brazil.
authors.forename: N E
authors.initials: NE
authors.lastname: Bufalo
authors.affiliation: University of Campinas (FCM - Unicamp)126, Tessalia Vieira de Camargo, Street. Cidade Universitaria Zeferino Vaz, Campinas - São Paulo, 13083-887 BrazilFederal University of Sao Paulo (Unifesp)669, Pedro Toledo Street, São Paulo-SP 04039-032, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Secolin
authors.affiliation: University of Campinas (FCM - Unicamp)126, Tessalia Vieira de Camargo, Street. Cidade Universitaria Zeferino Vaz, Campinas - São Paulo, 13083-887 BrazilFederal University of Sao Paulo (Unifesp)669, Pedro Toledo Street, São Paulo-SP 04039-032, Brazil.
authors.forename: L V M
authors.initials: LV
authors.lastname: Assumpção
authors.affiliation: University of Campinas (FCM - Unicamp)126, Tessalia Vieira de Camargo, Street. Cidade Universitaria Zeferino Vaz, Campinas - São Paulo, 13083-887 BrazilFederal University of Sao Paulo (Unifesp)669, Pedro Toledo Street, São Paulo-SP 04039-032, Brazil.
authors.forename: R M B
authors.initials: RM
authors.lastname: Maciel
authors.affiliation: University of Campinas (FCM - Unicamp)126, Tessalia Vieira de Camargo, Street. Cidade Universitaria Zeferino Vaz, Campinas - São Paulo, 13083-887 BrazilFederal University of Sao Paulo (Unifesp)669, Pedro Toledo Street, São Paulo-SP 04039-032, Brazil.
authors.forename: J M
authors.initials: JM
authors.lastname: Cerutti
authors.affiliation: University of Campinas (FCM - Unicamp)126, Tessalia Vieira de Camargo, Street. Cidade Universitaria Zeferino Vaz, Campinas - São Paulo, 13083-887 BrazilFederal University of Sao Paulo (Unifesp)669, Pedro Toledo Street, São Paulo-SP 04039-032, Brazil ward@fcm.unicamp.br.
authors.forename: L S
authors.initials: LS
authors.lastname: Ward
mesh_terms: D000328:Adult; D018278:Carcinoma, Neuroendocrine; D016022:Case-Control Studies; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D018797:Cell Cycle Proteins