Research Article The Polymorphisms of Epidermal Growth Factor-driven Signaling and Cancer Pathogenesis
Keywords:
epidermal growth factor, cancer, polymorphism, signaling pathway
Abstract
Background: Epidermal growth factor (EGF) is a stimulating protein for cell proliferation and differentiation. An amplification of its signaling pathway has been frequently reported in numerous malignant tumors. Specific polymorphisms of the genes encoding proteins involved in this cellular pathway may constitute risk factors for carcinogenesis. The aim of this study was to identify the most relevant polymorphisms of EGF and their signaling pathways and their relation to carcinogenesis.
Methods: The study included 40 full-text articles published between January 2010 and May 2020, extracted from PubMed, Scopus, Web of Science, and Science Direct databases in May 2020, using the following keywords: EGF OR epidermal growth factor AND polymorphism AND cancer OR neoplasia OR tumor.
Results: We identified relevant polymorphisms of the EGF signaling pathway that were involved in the development and progression of hepatocellular carcinoma, esophageal cancer, gastric cancer, colorectal cancer, glioma, lung cancer, breast cancer, cervical cancer, and head and neck cancer. Rs4444903 variants have been widely studied and the association with numerous tumors has been confirmed by multiple studies. Other frequently investigated polymorphisms are –191C/A and –216G>T.
Conclusion: The polymorphisms of EGF signaling pathway have been widely studied in connection to various malignancies. Some predisposing variants are common in different forms of cancer. These polymorphisms might be general risk factors for carcinogenesis
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elsevier.com/retrieve/pii/S2387020616000930
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biomedcentral.com/articles/10.1186/1471-230X-13-32
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growth-factor-gene-predicts-peer-reviewed-article-OTT
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//linkinghub.elsevier.com/retrieve/pii/S0016508511004161
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gene polymorphisms and hepatocellular carcinoma. Asian Pacific Journal of CancerPrevention, vol. 13, no. 12, pp. 6217–6220. Retrieved from: http://koreascience.or.kr/
journal/view.jsp?kj=POCPA9&py=2012&vnc=v13n12&sp=6217
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factor gene +61A/G polymorphism and the risk of hepatocellular carcinoma: a metaanalysis
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http://bmccancer.biomedcentral.com/articles/10.1186/s12885-015-1318-6
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liebertpub.com/doi/10.1089/gtmb.2012.0050
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polymorphism and liver cancer susceptibility: a meta-analysis and meta-regression.
Genetics and Molecular Research, vol. 13, no. 4, pp. 8066–8079. Retrieved from:
http://www.funpecrp.com.br/gmr/year2014/vol13-4/pdf/gmr3575.pdf
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hepatocellular carcinoma risk in chinese individuals: a meta-analysis. International
Journal of Clinical and Experimental Medicine, vol. 9, no. 3, pp. 5719–5727. Retrieved
from: http://www.ijcem.com/files/ijcem0009615.pdf
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growth factor 61*A/G polymorphism and hepatocellular carcinoma risk: a metaanalysis.
Asian Pacific Journal of Cancer Prevention, vol. 16, no. 7, pp. 3009–
3014. Retrieved from: http://koreascience.or.kr/journal/view.jsp?kj=POCPA9&py=
2015&vnc=v16n7&sp=3009
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receptor pathway genes and risk of esophageal squamous cell carcinoma and gastric
cancer in a Chinese population. PLoS One, vol. 8, no. 7, e68999. Retrieved from:
http://www.ncbi.nlm.nih.gov/pubmed/23874846
[18] Zhang, J., Zhan, Z., Wu, J., et al. (2013). Association among polymorphisms in EGFR
gene exons, lifestyle and risk of gastric cancer with gender differences in Chinese
Han subjects. PLoS ONE, vol. 8, no. 3, e59254. Retrieved from: https://dx.plos.org/
10.1371/journal.pone.0059254[19] Zhan, Z., Chen, Y., Wu, J., et al. (2013). Functional epidermal growth factor gene
polymorphisms and risk of gastric cancer. Oncology Letters, vol. 5, no. 2, pp. 631–
636. Retrived from: https://www.spandidos-publications.com/10.3892/ol.2012.1041
[20] Torres-Jasso, J. H., Marín, M. E., Luna Santiago, E. S., et al. (2015). EGFR gene
polymorphisms -216G>T and -191C>A are risk markers for gastric cancer in Mexican
population. Genetics and Molecular Research, vol. 14, no. 1, pp. 1802–1807. Retrieved
from: http://www.funpecrp.com.br/gmr/year2015/vol14-1/pdf/gmr4537.pdf
[21] Peng, Q., Li, S., Qin, X., et al. (2014). EGF +61A/G polymorphism contributes
to increased gastric cancer risk: evidence from a meta-analysis. Cancer Cell
International, vol. 14, no. 1, p. 134. Retrieved from: http://cancerci.biomedcentral.
com/articles/10.1186/s12935-014-0134-4
[22] Araújo, A. P., Costa, B. M., Pinto-Correia, A. L., et al. (2011). Association between
EGF +61A/G polymorphism and gastric cancer in caucasians. World Journal of
Gastroenterology, vol. 17, no. 4, pp. 488–492. Retrieved from: https://www.ncbi.nlm.
nih.gov/pmc/articles/PMC3027015/
[23] Chaleshi, V., Haghighi, M. M., Savabkar, S., et al. (2013). Correlation between the EGF
gene intronic polymorphism, rs2298979, and colorectal cancer. Oncology Letters,
vol. 6, no. 4, pp. 1079–1083. Retrieved from: https://www.spandidos-publications.
com/10.3892/ol.2013.1481
[24] Mustafa, O. H., Hamzeh, A. R., Ghabreau, L., et al. (2013). Allele frequencies of the
epidermal growth factor receptors polymorphism R521K in colorectal cancer patients
and healthy subjects indicate a risk-reducing effect of K521 in Syrian population.
North American Journal of Medical Sciences, vol. 5, no. 3, pp. 202–206. Retrieved
from: http://www.najms.org/text.asp?2013/5/3/202/109189
[25] Zhu, X., Shen, Y., and Xie, Q. (2019). The association between EGF A61G
polymorphism and risk of colorectal cancer in a Chinese population: a casecontrol
study. Bioscience Reports, vol. 39, no. 5, BSR20190495. Retrieved
from: https://portlandpress.com/bioscirep/article/doi/10.1042/BSR20190495/219161/
The-association-between-EGF-A61G-polymorphism-and
[26] Lau, T. P., Roslani, A. C., Lian, L. H., et al. (2014). Association between EGF and
VEGF functional polymorphisms and sporadic colorectal cancer in the Malaysian
population. Genetics and Molecular Research, vol. 13, no. 3, pp. 5555–5561.
Retrieved from: http://www.funpecrp.com.br/gmr/year2014/vol13-3/pdf/gmr3635.pdf
[27] Chaleshi, V., Haghighi, M. M., Javadi, G. R., et al. (2013). The effect of
5’untranslated region polymorphism in EGF gene, rs4444903, on colorectal cancer.Gastroenterology and Hepatology From Bed to Bench, vol. 6, no. 3, pp. 129–135.
Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/24834259
[28] Zhu, Y., Chen, Z. H., Jiang, H. G., et al. (2019). The genetic association between
EGF A61G polymorphism (rs4444903) and risk of colorectal cancer: an update metaanalysis
and trial sequential analysis. Medicine, vol. 98, no. 2, e14007. Retrieved
from: http://journals.lww.com/00005792-201901110-00041
[29] Costa, B. M., Viana-Pereira, M., Fernandes, R., et al. (2011). Impact of EGFR genetic
variants on glioma risk and patient outcome. Cancer Epidemiology, Biomarkers &
Prevention, vol. 20, no. 12, pp. 2610–2617. Retrieved from: http://www.ncbi.nlm.nih.
gov/pubmed/21960689
[30] Hou, W. G., Ai, W. B., Bai, X. G., et al. (2012). Genetic variation in the EGFR gene
and the risk of glioma in a Chinese Han population. PLoS ONE, vol. 7, no. 5, e37531.
Retrieved from: https://dx.plos.org/10.1371/journal.pone.0037531
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glioma risk in a Chinese population. BMC Cancer, vol. 10, p. 221. Retrieved from:
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