Skip to main content

Advertisement

SpringerLink
Log in

Association of Epidermal Growth Factor 61A>G, Survivin -31G>C, and EFNA1 -1732G>A Polymorphisms with Susceptibility to Colorectal Cancer

  • Original Research
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Background

Genetic polymorphisms play an important role in the development of colorectal cancer (CRC). Functional variants in the epidermal growth factor (EGF), survivin, and Ephrin A1 (EFNA1) genes have been previously reported to play a potential role in susceptibility to CRC, but these polymorphisms have not been well replicated. The aim of this study was to assess the association of the EGF 61A>G, Survivin -31G>C, and EFNA1 -1732G>A polymorphisms with the susceptibility to CRC in an Iranian population.

Methods

A total of 148 cases diagnosed with CRC and 160 healthy subjects were recruited. The EGF 61A>G, survivin -31G>C, and EFNA1 -1732G>A polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.

Results

Our data revealed that the homozygous mutant genotype (CC: OR = 2.895, 95% CI = 1.092–7.673, p = 0.033) and mutant allele (C: OR = 1.629, 95% CI = 1.152–2.303, p = 0.006) of the survivin -31G>C were associated with an increased risk of CRC in the Iranian population. However, our results failed to show an association between the EGF 61A>G and EFNA1 -1732G>A polymorphisms and CRC risk.

Conclusion

Our results revealed that the survivin -31G>C polymorphism might play an important role in development of CRC in Iranian population. However, no association of EGF 61A>G and EFNA1 -1732G>A polymorphisms with CRC risk was found.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Behtash N, Karimi Zarchi M, Deldar M. Preoperative prognostic factors and effects of adjuvant therapy on outcomes of early stage cervical cancer in Iran. Asian Pac J Cancer Prev. 2009;10(4):613–8.

    PubMed  Google Scholar 

  2. Zarchi MK, Akhavan A, Gholami H, Dehghani A, Naghshi M, Mohseni F. Evaluation of cervical cancer risk-factors in women referred to Yazd-Iran hospitals from 2002 to 2009. Asian Pac J Cancer Prev. 2010;11(2):537–8.

    Google Scholar 

  3. Mousavi A, Karimi Zarchi M, Modares Gilani M, Behtash N, Ghaemmaghami F, Shams M, et al. Radical hysterectomy in the elderly. World J Surg Oncol. 2008;6(1):38. https://doi.org/10.1186/1477-7819-6-38.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ghaemmaghami F, Zarchi MK, Gilani MM, Mousavi A, Behtash N, Ghasemi M. Uterine sarcoma: clinicopathological characteristics, treatment and outcome in Iran. Asian Pac J Cancer Prev. 2008;9(3):421–6.

    PubMed  Google Scholar 

  5. Chaleshi V, Haghighi MM, Javadi GR, Fatemi SR, Vahedi M, Zali MR. The effect of 5’untranslated region polymorphism in EGF gene, rs4444903, on colorectal cancer. Gastroenterol Hepatol Bed Bench. 2013;6(3):129–35.

    PubMed  PubMed Central  Google Scholar 

  6. Parsafar S, Hematti S, Ghorbani F, Safari F, Tavassoli M. Polymorphic GT dinucleotide repeat in the PIK3CA gene and risk of colorectal cancer. Cancer Biomarkers. 2015;15(4):397–403.

    Article  CAS  PubMed  Google Scholar 

  7. Fatehi Z, Amirmahani F, Tavassoli M. Association study of TAAAA polymorphism in the first intron of p53 gene with risk of colorectal cancer in Iranian population. Egypt J Med Hum Genet. 2019;20(1):19.

    Article  Google Scholar 

  8. Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 2009;22(4):191–7.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14(2):89–103.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Kolahdoozan S, Sadjadi A, Radmard AR, Khademi H. Five common cancers in Iran. Arch Iran Med. 2010;13(2):143–6.

    PubMed  Google Scholar 

  11. Jafari-Nedooshan J, Dastgheib SA, Kargar S, Zare M, Raee-Ezzabadi A, Heiranizadeh N, et al. Association of IL-6 -174 G > C polymorphism with susceptibility to colorectal cancer and gastric cancer: a systematic review and meta-analysis. Acta Med (Hradec Kralove). 2019;62(4):137–46.

    Article  CAS  Google Scholar 

  12. Basavaraju U, Shebl FM, Palmer AJ, Berry S, Hold GL, El-Omar EM, et al. Cytokine gene polymorphisms, cytokine levels and the risk of colorectal neoplasia in a screened population of Northeast Scotland. Eur J Cancer Prev. 2015;24(4):296–304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sameer AS. Colorectal cancer: Molecular mutations and polymorphisms. Front Oncol. 2013;3:114.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Peters U, Bien S, Zubair N. Genetic architecture of colorectal cancer. Gut. 2015;64(14):1623–36.

    Article  CAS  PubMed  Google Scholar 

  15. Pino MS, Chung DC. The Chromosomal Instability pathway in colon cancer. Gastroenterology. 2010;138(6):2059–72.

    Article  CAS  PubMed  Google Scholar 

  16. Centelles JJ. General aspects of colorectal cancer. ISRN Oncol. 2012;2012:1–19. https://doi.org/10.5402/2012/139268.

    Article  CAS  Google Scholar 

  17. Aceto GM, Catalano T, Curia MC, Tong Q. Molecular aspects of colorectal adenomas: the interplay among microenvironment, oxidative stress, and predisposition. Biomed Res Int. 2020;11:1–19.

    Article  Google Scholar 

  18. Mazloom Z, Tabei SMB, Bahmanpour S, Tabatabaee HR, Naeni MA. Relation of red blood cell’ folate and methylenetetrahedrofolate reductase C677T polymorphism to colorectal adenoma. Tehran Univ Med J. 2014;72(8):515–25.

    Google Scholar 

  19. Kastrinos F, Syngal S. Inherited colorectal cancer syndromes. Cancer J. 2011;17(6):405–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chen E, Xu X, Liu T. Hereditary nonpolyposis colorectal cancer and cancer syndromes: recent basic and clinical discoveries. J Oncol. 2018;2018:3979135–11. https://doi.org/10.1155/2018/3979135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Valle L, Vilar E, Tavtigian SV, Stoffel EM. Genetic predisposition to colorectal cancer: syndromes, genes, classification of genetic variants and implications for precision medicine. J Pathol. 2019;247:574–88.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Jasperson KW, Tuohy TM, Neklason DW, Burt RW. Hereditary and familial colon cancer. Gastroenterology. 2010;138(6):2044–58.

    Article  CAS  PubMed  Google Scholar 

  23. Kumar B, Bhat ZI, Bansal S, Saini S, Naseem A, Wahabi K, et al. Association of mitochondrial copy number variation and T16189C polymorphism with colorectal cancer in North Indian population. Tumor Biol. 2017;39(11):101042831774029.

    Article  Google Scholar 

  24. Banday MZ, Balkhi HM, Sameer AS, Chowdri NA, Haq E. Strong association of interleukin-6 − 174G/C promoter single nucleotide polymorphism with a decreased risk of colorectal cancer in ethnic Kashmiri population: a case control study. Tumor Biol. 2017;39(3):101042831769594.

    Article  Google Scholar 

  25. Namazi A, Abedinzadeh M, Nourbaksh P, Neamatzadeh H. Association between the XRCC3 Thr241Met polymorphism and risk of colorectal cancer: a meta analysis of 5,193 cases and 6,645 controls. Asian Pac J Cancer Prev. 2015;16(6):2263–8.

    Article  PubMed  Google Scholar 

  26. Haghshenas MR, Hosseini SV, Mahmoudi M, Saberi-Firozi M, Farjadian S, Ghaderi A. IL-18 serum level and IL-18 promoter gene polymorphism in Iranian patients with gastrointestinal cancers. J Gastroenterol Hepatol. 2009;24(6):1119–22.

    Article  CAS  PubMed  Google Scholar 

  27. Simonian M, Mosallaei M, Khosravi S, Salehi R. rs12904 polymorphism in the 3’-untranslated region of ephrin A1 ligand and the risk of sporadic colorectal cancer in the Iranian population. J Can Res Ther. 2019;15(1):15–9.

    CAS  Google Scholar 

  28. Huang J, Wei Y, Zhou X, Wang L, Huang M, Wang J. The association between survivin -31G > C polymorphism and susceptibility to sporadic colorectal cancer in a Southern Chinese population. J Can Res Ther. 2018;15:82–8.

    Google Scholar 

  29. Jiang G, Yu K, Shao L, Yu X, Hu C, Qian P, et al. Association between epidermal growth factor gene +61A/G polymorphism and the risk of hepatocellular carcinoma: a meta-analysis based on 16 studies. BMC Cancer. 2015;15(1):314.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Li F. Discovery of survivin inhibitors and beyond: FL118 as a proof of concept. Int Rev Cell Mol Biol. 2013;305:217–52.

    Article  CAS  PubMed  Google Scholar 

  31. Khan S, Bennit HF, Wall NR. The emerging role of exosomes in survivin secretion. Histol Histopathol. 2015;30(1):43–50.

    CAS  PubMed  Google Scholar 

  32. Ieguchi K, Maru Y. Roles of EphA1/A2 and ephrin-A1 in cancer. Cancer Sci. 2019;110:841–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cui XD, Lee MJ, Yu GR, Kim IH, Yu HC, Song EY, et al. EFNA1 ligand and its receptor EphA2: potential biomarkers for hepatocellular carcinoma. Int J Cancer. 2009;126(4):940–9.

    Google Scholar 

  34. Bahrami R, Shajari A, Aflatoonian M, Noorishadkam M, Akbarian-Bafghi MJ, Morovati-Sharifabad M, et al. Association of REarranged during transfection (RET) c.73 + 9277 T > C and c.135G > a polymorphisms with susceptibility to Hirschsprung disease: a systematic review and meta-analysis. Fetal Pediatr Pathol. 2019:1–15. https://doi.org/10.1080/15513815.2019.1672225.

  35. Amersi F, Agustin M, Ko CY. Colorectal cancer: epidemiology, risk factors, and health services. Clin Colon Rectal Surg. 2005;18(3):133–40.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zhu X, Shen Y, Xie Q. The association between EGF A61G polymorphism and risk of colorectal cancer in a Chinese population: a case-control study. Biosci Rep. 2019;39(5):BSR20190495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Piao Y, Liu Z, Ding Z, Xu L, Guo F, Sun Q, et al. EGF +61A > G polymorphism and gastrointestinal cancer risk: a HuGE review and meta-analysis. Gene. 2013;519(1):26–33.

    Article  CAS  PubMed  Google Scholar 

  38. Heidari Z, Sagheb HM, Hakimi A, Moudi B. Evaluation of immunohistochemical expression of survivin and its correlation with -31G/C gene polymorphism in colorectal cancer. Med Mol Morphol. 2019;52(2):82–9.

    Article  CAS  PubMed  Google Scholar 

  39. Budak M, Bozkurt C, Cetin SE, Tuncel H. The -31 G/C promoter gene polymorphism of surviving in Turkish colorectal cancers patients. Ceylon Med J. 2018;63(3):119–23.

    Article  CAS  PubMed  Google Scholar 

  40. Alford S, Watson-Hurthig A, Scott N, Carette A, Lorimer H, Bazowski J, et al. Soluble ephrin a1 is necessary for the growth of HeLa and SK-BR3 cells. Cancer Cell Int. 2010;10:41. https://doi.org/10.1186/1475-2867-10-41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Li Y, Nie Y, Cao J, Tu S, Lin Y, Du Y, et al. G-A variant in miR-200c binding site of EFNA1 alters susceptibility to gastric cancer. Mol Carcinog. 2014;53(3):219–29.

    Article  PubMed  Google Scholar 

  42. Mao YY, Jing FY, Jin MJ, Li YJ, Ding Y, Guo J, et al. rs12904 polymorphism in the 3’UTR of EFNA1 is associated with colorectal cancer susceptibility in a Chinese population. Asian Pac J Cancer Prev. 2013;14(9):5037–41.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the anonymous reviewers for reviewing this manuscript. Moreover, this study is dedicated to the memory of Kurdish-Iranian family (Rasoul Iran-Nejad, 35; Shiva Mohammad Panahi, 35; Anita, nine; and Armin, six) who died when their migrant boat capsized in the English Channel on 28 October 2020.

Funding

This work was supported by Tehran North Branch, Islamic Azad University, Tehran, Iran.

Author information

Authors and Affiliations

  1. Department of Medical Laboratory Sciences, School of Paramedical Science, Shiraz University of Medical Sciences, Shiraz, Iran

    Fatemeh Asadian

  2. Department of Advanced Medical Sciences and Technologies, Islamic Azad University, Science and Research Branch, Tehran, Iran

    Mohammadamin Ghadyani

  3. Department of Internal Medicine, Yazd Branch, Islamic Azad University, Yazd, Iran

    Mohamad Hossein Antikchi

  4. Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Seyed Alireza Dastgheib

  5. Mother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Hossein Neamatzadeh & Sahel Khajehnoori

  6. Department of Medical Genetics, Shahid Sadoughi University of Medical Science, Yazd, Iran

    Hossein Neamatzadeh & Sahel Khajehnoori

  7. Hematology and Oncology Research Center, Shahid Sadoughi University of Medical Science, Yazd, Iran

    Elnaz Sheikhpour

  8. Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Seyed Sajjad Tabei

Authors
  1. Fatemeh Asadian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammadamin Ghadyani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohamad Hossein Antikchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seyed Alireza Dastgheib
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hossein Neamatzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elnaz Sheikhpour
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sahel Khajehnoori
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Seyed Sajjad Tabei
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MAG and MHA conceptualized the study. MAG, FA, and MHA designed the study and the interview guide. Data analysis was done by SKH and HN. Manuscript was written and critically reviewed by SKH and SST. SAD is revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mohamad Hossein Antikchi.

Ethics declarations

Conflicting Interests

The authors declared that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Asadian, F., Ghadyani, M., Antikchi, M.H. et al. Association of Epidermal Growth Factor 61A>G, Survivin -31G>C, and EFNA1 -1732G>A Polymorphisms with Susceptibility to Colorectal Cancer. J Gastrointest Canc 53, 78–83 (2022). https://doi.org/10.1007/s12029-020-00551-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-020-00551-4

Keywords

Search

Navigation