Polymorphisms of IL-4 and IL-4R are associated to some demographic characteristics of differentiated thyroid cancer pati
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ORIGINAL ARTICLE
Polymorphisms of IL-4 and IL-4R are associated to some demographic characteristics of differentiated thyroid cancer patients but are not determinants of risk in the Brazilian population Mariana Bonjiorno Martins 1 Fernando de Assis Batista1 Natassia Elena Bufalo1 Karina Colombera Peres1 Murilo Meneghetti1 Ligia Vera Montali da Assumpção2 Laura Sterian Ward1 ●
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Received: 30 May 2020 / Accepted: 28 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Background IL-4 is known to present abnormal expression in thyroid tumors and SNPs in the IL-4 and its receptor IL-4R genes are associated to risk and mortality of various types of cancer. Methods In order to evaluate their role in differentiated thyroid cancer (DTC), we investigated genetic frequencies of two IL-4 promoter SNPs (rs2070874 C>T, rs2243250 C>T) and four non-synonymous SNPs of the IL-4R gene (rs1805010 A>G, rs1805012 C>T, rs1805013 C>T, rs1801275 A>G) in 300 DTC patients matched to 300 controls. All patients were managed according to current guidelines and followed-up for a period of 12–252 months (69.20 ± 52.70 months). Results Although none of the six investigated SNPs showed association with risk of DTC, rs1805010 was associated with age of diagnosis and the SNPs rs1805012 and rs1801275 were associated to gender. Further, in-silico analysis showed that all these three SNPs were able to cause decreased stability of the protein. We were not able to demonstrate any other association to clinical features of aggressiveness or to patients’ prognosis. Conclusions These findings indicate that although genetic variants in IL-4 and IL-4R do not influence the risk or outcome of DTC patients, their influence on the behavior of thyroid tumors deserves further investigation. Keywords SNPs polymorphisms Interleukins Cancer susceptibility Thyroid cancer ●
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Introduction The incidence of thyroid cancer has rapidly increased in many countries, including USA, China, Korea, and Brazil,
These authors contributed equally: Mariana Bonjiorno Martins, Fernado de Assis Batista Supplementary information The online version of this article (https:// doi.org/10.1007/s12020-020-02486-z) contains supplementary material, which is available to authorized users. * Mariana Bonjiorno Martins [email protected] 1
Laboratory of Cancer Molecular Genetics, School of Medical Sciences (FCM), University of Campinas (Unicamp), 126, Tessália Vieira de Camargo St., Campinas, SP, Brazil
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Division of Endocrinology, Department of Medicine, Faculty of Medical Sciences—University of Campinas (Unicamp), 251, Vital Brazil St., Campinas, SP, Brazil
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with a higher rate for differentiated thyroid cancer (DTC) [1–4], while the incidence rate of undifferentiated thyroid cancer appears to be increasing in the United States, but its overall incidence still remains low [5]. The latest release of the GLOBOCAN database estimates that 562,000 patients were diagnosed with DTC worldwide in 2018 [6]. In Brazi
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