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Published in: Endocrine 1/2022

01-01-2022 | Thyroid Cancer | Original Article

The effect of VAV3 polymorphisms on thyroid cancer

Authors: Wanli Ren, Chongwen Xu, Shiyang Wang, Huajing Li, Hao Dai, Fangli Yang, Yuan Shao, Yanxia Bai

Published in: Endocrine | Issue 1/2022

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Abstract

Background

The incidence of thyroid cancer is rising rapidly in China, but there are few studies on the risk factors of thyroid cancer in the Chinese Han population.

Methods

We performed this case–control study of 510 patients and 509 controls to for determine the linkage of VAV3 variants (rs17019602, rs7521681, rs4915076, and rs1777451) with thyroid cancer susceptibility by computing the odds ratio (OR) and 95% confidence intervals (CI). Multi-factor dimension reduction (MDR) analysis was conducted to assess interaction of VAV3 genetic variants.

Results

We found that rs7521681 was remarkably related to a higher risk of thyroid cancer (OR = 1.74, p = 0.012), whereas rs4915076 (OR = 0.66, p = 0.001) significantly decreased thyroid cancer susceptibility. Stratified analyses showed that rs4915076 had a protective role in thyroid cancer in both ages >45 years (OR = 0.70, p = 0.017) and age ≤45 years (OR = 0.63, p = 0.007). Rs17019602 could increase the susceptibility of thyroid cancer in men (OR = 4.76, p = 0.049). Rs7521681 was related to an increased risk of thyroid cancer in women (OR = 1.97, p = 0.012). Rs4915076 could protect individuals from thyroid cancer both in men (OR = 0.60, p = 0.031) and women (OR = 0.68, p = 0.010). Moreover, rs4915076 was the best single-locus model to predict thyroid cancer. Interestingly, the interaction model of rs17019602, rs7521681, rs4915076, rs1777451, and age was a candidate gene-environment model.

Conclusion

Our results indicated VAV3 variants were associated with thyroid cancer, which provides a new sight into etiology of thyroid cancer.
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Literature
1.
go back to reference W.R. Burns, M.A. Zeiger, Differentiated thyroid cancer. Seminars in Oncology 37, 557–566 (2010)CrossRef W.R. Burns, M.A. Zeiger, Differentiated thyroid cancer. Seminars in Oncology 37, 557–566 (2010)CrossRef
2.
go back to reference J. Jonklaas et al. The impact of age and gender on papillary thyroid cancer survival. J. of Clin. Endocrinol. & Metab 6, 878–887 (2012)CrossRef J. Jonklaas et al. The impact of age and gender on papillary thyroid cancer survival. J. of Clin. Endocrinol. & Metab 6, 878–887 (2012)CrossRef
3.
go back to reference Y.Q. Liu, S.Q. Zhang, W.Q. Chen, L.L. Chen, R.S. Zheng, [Trend of incidence and mortality on thyroid cancer in China during 2003 - 2007]. Zhonghua Liu Xing Bing Xue Za Zhi 33, 1044–1048 (2012)PubMed Y.Q. Liu, S.Q. Zhang, W.Q. Chen, L.L. Chen, R.S. Zheng, [Trend of incidence and mortality on thyroid cancer in China during 2003 - 2007]. Zhonghua Liu Xing Bing Xue Za Zhi 33, 1044–1048 (2012)PubMed
7.
go back to reference H.Y. Son et al. Genome-wide association and expression quantitative trait loci studies identify multiple susceptibility loci for thyroid cancer. Nat. Commun. 8, 15966 (2017)CrossRef H.Y. Son et al. Genome-wide association and expression quantitative trait loci studies identify multiple susceptibility loci for thyroid cancer. Nat. Commun. 8, 15966 (2017)CrossRef
10.
go back to reference L. Zeng, P. Sachdev, L. Yan, J.L. Chan, L.H. Wang, Vav3 mediates receptor protein tyrosine kinase signaling, regulates gtpase activity, modulates cell morphology, and induces cell transformation. Mol. & Cell. Biol. 20, 9212–9224 (2001)CrossRef L. Zeng, P. Sachdev, L. Yan, J.L. Chan, L.H. Wang, Vav3 mediates receptor protein tyrosine kinase signaling, regulates gtpase activity, modulates cell morphology, and induces cell transformation. Mol. & Cell. Biol. 20, 9212–9224 (2001)CrossRef
11.
go back to reference K.-T. Lin et al. Vav3-Rac1 signaling regulates prostate cancer metastasis with elevated Vav3 expression correlating with prostate cancer progression and posttreatment recurrence. Cancer Res. 72, 3000–3009 (2012)CrossRef K.-T. Lin et al. Vav3-Rac1 signaling regulates prostate cancer metastasis with elevated Vav3 expression correlating with prostate cancer progression and posttreatment recurrence. Cancer Res. 72, 3000–3009 (2012)CrossRef
12.
go back to reference H. Aguilar et al. VAV3 mediates resistance to breast cancer endocrine therapy. Breast Cancer Res. 16, 53–69 (2014) H. Aguilar et al. VAV3 mediates resistance to breast cancer endocrine therapy. Breast Cancer Res. 16, 53–69 (2014)
13.
go back to reference G. Riesco-Eizaguirre, P. Santisteban, New insights in thyroid follicular cell biology and its impact in thyroid cancer therapy. Endocrine Rel. Cancer 14, 957–977 (2008)CrossRef G. Riesco-Eizaguirre, P. Santisteban, New insights in thyroid follicular cell biology and its impact in thyroid cancer therapy. Endocrine Rel. Cancer 14, 957–977 (2008)CrossRef
14.
go back to reference N. Perretta-Tejedor et al. Association of VAV2 and VAV3 polymorphisms with cardiovascular risk factors. Sci. Rep. 7, 41875 (2017)CrossRef N. Perretta-Tejedor et al. Association of VAV2 and VAV3 polymorphisms with cardiovascular risk factors. Sci. Rep. 7, 41875 (2017)CrossRef
15.
go back to reference M. Liu, N. Miao, Y. Zhu, C.Y. Gu, Q.X. Li, Association between polymorphism in Vav3 genes and risk of primary prostatic cancer in Chinese Han population. Zhonghua bing li xue za zhi Chinese j. of pathol. 45, 451–456 (2016) M. Liu, N. Miao, Y. Zhu, C.Y. Gu, Q.X. Li, Association between polymorphism in Vav3 genes and risk of primary prostatic cancer in Chinese Han population. Zhonghua bing li xue za zhi Chinese j. of pathol. 45, 451–456 (2016)
16.
go back to reference R. Usategui-Martín, I. Calero-Paniagua, J. García-Aparicio, L. Corral-Gudino, R.G. Sarmiento, VAV3 gene polymorphism is associated with Paget’s disease of bone. Genetic Testing & Mol. Biomarkers 20, 335–337 (2016)CrossRef R. Usategui-Martín, I. Calero-Paniagua, J. García-Aparicio, L. Corral-Gudino, R.G. Sarmiento, VAV3 gene polymorphism is associated with Paget’s disease of bone. Genetic Testing & Mol. Biomarkers 20, 335–337 (2016)CrossRef
17.
go back to reference G. Palomba et al. Genome-wide association study of susceptibility loci for breast cancer in Sardinian population. Bmc Cancer 15, 383 (2015)CrossRef G. Palomba et al. Genome-wide association study of susceptibility loci for breast cancer in Sardinian population. Bmc Cancer 15, 383 (2015)CrossRef
18.
go back to reference D. Liu, Z.G. Zhao, Z.L. Jiao, H.J. Li, Identifying differential expression genes and single nucleotide variations using RNA-seq in metastatic melanoma. Genetics & Molecular Research Gmr 13, 8153–8162 (2014)CrossRef D. Liu, Z.G. Zhao, Z.L. Jiao, H.J. Li, Identifying differential expression genes and single nucleotide variations using RNA-seq in metastatic melanoma. Genetics & Molecular Research Gmr 13, 8153–8162 (2014)CrossRef
19.
go back to reference C. Wu, G. Li, W. Li, The interaction effect of rs4077515 and rs17019602 increases the susceptibility to IgA nephropathy. Oncotarget 8, 76492–76497 (2017)CrossRef C. Wu, G. Li, W. Li, The interaction effect of rs4077515 and rs17019602 increases the susceptibility to IgA nephropathy. Oncotarget 8, 76492–76497 (2017)CrossRef
20.
go back to reference O. Daisuke et al. Identification of a Hashimoto Thyroiditis susceptibility locus via a genome-wide comparison with Graves' disease. J. of Clin. Endocrinol. & Metab 2, 319–324 (2015) O. Daisuke et al. Identification of a Hashimoto Thyroiditis susceptibility locus via a genome-wide comparison with Graves' disease. J. of Clin. Endocrinol. & Metab 2, 319–324 (2015)
22.
go back to reference A. et al. Association of gene polymorphisms with coronary artery disease in low- or high-risk subjects defined by conventional risk factors. ACC Current J. Rev. 42, 1429–1437 (2004) A. et al. Association of gene polymorphisms with coronary artery disease in low- or high-risk subjects defined by conventional risk factors. ACC Current J. Rev. 42, 1429–1437 (2004)
23.
go back to reference H. Aguilar et al. VAV3 mediates resistance to breast cancer endocrine therapy. Breast Cancer Res. 16, 1–16 (2014). H. Aguilar et al. VAV3 mediates resistance to breast cancer endocrine therapy. Breast Cancer Res. 16, 1–16 (2014).
24.
go back to reference Y.H. Uen et al. VAV3 oncogene expression in colorectal cancer: Clinical aspects and functional characterization. Scientific Reports 5, 9360 (2015)CrossRef Y.H. Uen et al. VAV3 oncogene expression in colorectal cancer: Clinical aspects and functional characterization. Scientific Reports 5, 9360 (2015)CrossRef
25.
go back to reference M. Xie et al. The long intergenic non-protein coding RNA 707 promotes proliferation and metastasis of gastric cancer by interacting with mRNA stabilizing protein HuR. Cancer Letters 68, 67–79 (2018) M. Xie et al. The long intergenic non-protein coding RNA 707 promotes proliferation and metastasis of gastric cancer by interacting with mRNA stabilizing protein HuR. Cancer Letters 68, 67–79 (2018)
Metadata
Title
The effect of VAV3 polymorphisms on thyroid cancer
Authors
Wanli Ren
Chongwen Xu
Shiyang Wang
Huajing Li
Hao Dai
Fangli Yang
Yuan Shao
Yanxia Bai
Publication date
01-01-2022
Publisher
Springer US
Published in
Endocrine / Issue 1/2022
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-021-02827-6

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