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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References
W.R. Burns, M.A. Zeiger, Differentiated thyroid cancer. Seminars in Oncology 37, 557–566 (2010)
J. Jonklaas et al. The impact of age and gender on papillary thyroid cancer survival. J. of Clin. Endocrinol. & Metab 6, 878–887 (2012)
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)
D. Schmid, G. Behrens, C. Jochem, M. Keimling, M. Leitzmann, Physical activity, diabetes, and risk of thyroid cancer: a systematic review and meta-analysis. European journal of epidemiology 28, 945–958 (2013). https://doi.org/10.1007/s10654-013-9865-0
H. Arem, E. Loftfield Cancer epidemiology: a survey of modifiable risk factors for prevention and survivorship. Am. j. of lifestyle med. 12, 200–210 (2018). https://doi.org/10.1177/1559827617700600
J. Kim, J.E. Gosnell, S.A. Roman, Geographic influences in the global rise of thyroid cancer. 16, 17–29, https://doi.org/10.1038/s41574-019-0263-x (2020)
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)
W. Zhou, & B. Brumpton, GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer. 11, 3981, https://doi.org/10.1038/s41467-020-17718-z (2020)
S.S. Song, S. Huang, S. Park, Association of polygenetic risk scores related to cell differentiation and inflammation with thyroid cancer risk and genetic interaction with dietary intake. 13, https://doi.org/10.3390/cancers13071510 (2021)
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)
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)
H. Aguilar et al. VAV3 mediates resistance to breast cancer endocrine therapy. Breast Cancer Res. 16, 53–69 (2014)
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)
N. Perretta-Tejedor et al. Association of VAV2 and VAV3 polymorphisms with cardiovascular risk factors. Sci. Rep. 7, 41875 (2017)
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)
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)
G. Palomba et al. Genome-wide association study of susceptibility loci for breast cancer in Sardinian population. Bmc Cancer 15, 383 (2015)
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)
C. Wu, G. Li, W. Li, The interaction effect of rs4077515 and rs17019602 increases the susceptibility to IgA nephropathy. Oncotarget 8, 76492–76497 (2017)
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)
N. Horita, T. Kaneko, Genetic model selection for a case-control study and a meta-analysis. Meta gene 5, 1–8 (2015). https://doi.org/10.1016/j.mgene.2015.04.003
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)
H. Aguilar et al. VAV3 mediates resistance to breast cancer endocrine therapy. Breast Cancer Res. 16, 1–16 (2014).
Y.H. Uen et al. VAV3 oncogene expression in colorectal cancer: Clinical aspects and functional characterization. Scientific Reports 5, 9360 (2015)
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)
S. Kwak et al. A genome-wide association study on thyroid function and anti-thyroid peroxidase antibodies in Koreans. Human mol. genet. 23, 4433–4442 (2014). https://doi.org/10.1093/hmg/ddu145
N. Eriksson et al. Novel associations for hypothyroidism include known autoimmune risk loci. PloS one 7, e34442 (2012). https://doi.org/10.1371/journal.pone.0034442
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Ren, W., Xu, C., Wang, S. et al. The effect of VAV3 polymorphisms on thyroid cancer. Endocrine 75, 178–184 (2022). https://doi.org/10.1007/s12020-021-02827-6
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DOI: https://doi.org/10.1007/s12020-021-02827-6