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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

Endocrine Aims and scope Submit manuscript

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.

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Acknowledgements

The authors would like to thank the Fundação de Amparo à Pesquisa do Estado São Paulo (FAPESP; São Paulo, Brazil) for the funding for this work.

Funding

Laboratory of Cancer Molecular Genetics which is responsible for creating resources for this work has received funding from Fundação de Amparo à Pesquisa do Estado São Paulo (FAPESP; São Paulo, Brazil) through Grant 2012/22726-0 to LSW. MBM was supported by the FAPESP’s fellowship 2012/16830-0. The funding agencies did not influence on the design of the study and collection, analysis, nor had they any influence on the decision to submit the manuscript for publication.

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Conception and design: M.B.M., F.A.B., L.V.M.A., and L.S.W. Acquisition of data: M.B.M. and F.A.B. Literature search and data analysis: M.B.M., F.A.B., N.E.F., K.C.P., M.M., and L.S.W. Statistical analysis: M.B.M., F.A.B., N.E.F., and K.C,P. Writing, review, and/or revision of the paper: M.B.M., F.A.B., and L.S.W. Study supervision: L.S.W. All authors approved the final paper.

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Correspondence to Mariana Bonjiorno Martins.

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Martins, M.B., de Assis Batista, F., Bufalo, N.E. et al. 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. Endocrine 72, 470–478 (2021). https://doi.org/10.1007/s12020-020-02486-z

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