Polymorphisms of cell cycle control genes influence the development of sporadic medullary thyroid carcinoma

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dc.contributor.authorBarbieri, R. B.
dc.contributor.authorBufalo, N. E.
dc.contributor.authorSecolin, Rodrigo
dc.contributor.authorAssumpcao, L. V. M.
dc.contributor.authorMaciel, Rui Monteiro de Barros [UNIFESP]
dc.contributor.authorCerutti, Janete Maria [UNIFESP]
dc.contributor.authorWard, Laura Sterian [UNIFESP]
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:38:13Z
dc.date.available2016-01-24T14:38:13Z
dc.date.issued2014-12-01
dc.description.abstractBackground: 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 CDKN2 Agene 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).Conclusion: 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.en
dc.description.affiliationUniv Campinas FCM Unicamp, BR-13083887 Campinas, SP, Brazil
dc.description.affiliationFed Univ São Paulo Unifesp, BR-04039032 São Paulo, Brazil
dc.description.affiliationUnifespFed Univ São Paulo Unifesp, BR-04039032 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIDFAPESP: 07067-5
dc.format.extent761-767
dc.identifierhttp://dx.doi.org/10.1530/EJE-14-0461
dc.identifier.citationEuropean Journal of Endocrinology. Bristol: Bioscientifica Ltd, v. 171, n. 6, p. 761-767, 2014.
dc.identifier.doi10.1530/EJE-14-0461
dc.identifier.issn0804-4643
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/38483
dc.identifier.wosWOS:000345567700017
dc.language.isoeng
dc.publisherBioscientifica Ltd
dc.relation.ispartofEuropean Journal of Endocrinology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titlePolymorphisms of cell cycle control genes influence the development of sporadic medullary thyroid carcinomaen
dc.typeinfo:eu-repo/semantics/article
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