Document Type : Original Article(s)

Authors

1 Shiraz Endocrine and Metabolism Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

2 Cancer Immunology Group, Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: The aim of this study was to investigate the association between thyroid cancer and 16C/A single nucleotide polymorphism (SNP) in C-C motif chemokine 22 (CCL22) as well as 1014C/T SNP in C-C chemokine receptor type 4 (CCR4).
Method: In this case-control study, polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP) was performed for 113 thyroid cancer patients and 112 age-sex matched healthy controls to investigate the genotype distribution.
Results: At position 16C/A in CCL22, 95 patients (84.3%) were found to have CC genotype, while 17 individuals (14.8%) inherited CA genotype and 1 (0.9%) had AA genotype. In the control group, 92 volunteers (82.1%) inherited CC genotype, 18 individuals (16.1%) had CA genotype, and 2 (1.8%) had AA genotype. The frequency of CC, CT, and TT genotypes of 1014C/T SNP in CCR4 gene was 60 (53.1%), 43 (38.1%), and 10 (8.8%) in the patients, and 57 (53.3%), 43 (40.2%), and 7 (6.5%) in the control group, respectively. There were no statistically significant differences between the patients and controls in terms of 16C/A polymorphism in CCL22 (P = 0.816) and 1014C/T SNP in CCR4 1014C/T gene position (P = 0.801). Nevertheless, the study of their association indicated that inheriting the CC genotype of CCR4 was significantly associated with higher stages (stages 3 and 4) in thyroid cancer.
Conclusion: 1014C/T genetic variation in CCR4 and 16C/A polymorphism in CCL22 were not found to have a role in genetic susceptibility to thyroid cancer. Inheriting CC genotype at 1014 locus in CCR4 may; however, affect cancer progression in patients with thyroid cancer.

Keywords

How to cite this article:

Dabbaghmanesh MH, Rezaei B, Haghshenas MR, Montazeri-Najafabady N, Mohammadian Amiri R, Erfani N. CCR4 1014C/T and CCL22 16C/A genetic variations in Iranian patients with thyroid cancer. Middle East J Cancer. 2022;13(3):404-10. doi: 10.30476/mejc.2021.87469.1421.

  1. Jones AM, Howarth KM, Martin L, Gorman M, Mihai R, Moss L, et al. Thyroid cancer susceptibility polymorphisms: confirmation of loci on chromosomes 9q22 and 14q13, validation of a recessive 8q24 locus and failure to replicate a locus on 5q24. J Med Genet. 2012;49(3):158-63. doi: 10.1136/jmedgenet-2011-100586.
  2. Sipos JA, Mazzaferri EL. Thyroid cancer epidemiology and prognostic variables. Clin Oncol (R Coll Radiol). 2010;22(6):395-404. doi: 10.1016/j.clon.2010.05.004.
  3. Rahbari R, Zhang L, Kebebew E. Thyroid cancer gender disparity. Future Oncol. 2010;6(11):1771-9. doi: 10.2217/fon.10.127.
  4. Gudmundsson J, Sulem P, Gudbjartsson DF, Jonasson JG, Sigurdsson A, Bergthorsson JT, et al. Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations. Nat Genet. 2009;41(4):460-4. doi: 10.1038/ng.339.
  5. Cunha LL, Marcello MA, Morari EC, Nonogaki S, Conte FF, Gerhard R, et al. Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation. Endocr Relat Cancer. 2013;20(1):103-10. doi: 10.1530/ERC-12-0313.
  6. Liotta LA, Kohn EC. The microenvironment of the tumour–host interface. Nature. 2001;411(6835):375-9. doi: 10.1038/35077241.
  7. Ben-Baruch A. The multifaceted roles of chemokines in malignancy. Cancer Metastasis Rev. 2006;25(3):357-71. doi: 10.1007/s10555-006-9003-5.
  8. Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity. 2000; 12(2):121-7. DOI: 10.1016/s1074-7613(00)80165-x.
  9. O'Hayre M, Salanga CL, Handel TM, Allen SJ. Chemokines and cancer: migration, intracellular signalling and intercellular communication in the microenvironment. Biochem J. 2008;409(3):635-49. doi: 10.1042/BJ20071493.
  10. Ishida T, Ueda R. CCR4 as a novel molecular target for immunotherapy of cancer. Cancer Sci. 2006;97(11):1139-46. doi: 10.1111/j.1349-7006.2006.00307.x.
  11. Röhrle N, Knott MML, Anz D. CCL22 Signaling in the Tumor Environment. Adv Exp Med Biol. 2020;1231:79-96. doi: 10.1007/978-3-030-36667-4_8.
  12. Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001;410(6824):50-6. doi: 10.1038/35065016.
  13. Taichman RS, Cooper C, Keller ET, Pienta KJ, Taichman NS, McCauley LK. Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Res. 2002;62(6):1832-7.
  14. Yasumoto K, Koizumi K, Kawashima A, Saitoh Y, Arita Y, Shinohara K, et al. Role of the CXCL12/CXCR4 axis in peritoneal carcinomatosis of gastric cancer. Cancer Res. 2006;66(4):2181-7. doi: 10.1158/0008-5472.CAN-05-3393. Erratum in: Cancer Res. 2006;66(7):3957.
  15. Kimsey TF, Campbell AS, Albo D, Wilson M, Wang TN. Co-localization of macrophage inflammatory protein-3alpha (Mip-3alpha) and its receptor, CCR6, promotes pancreatic cancer cell invasion. Cancer J. 2004;10(6):374-80. doi: 10.1097/00130404-200411000-00007. Erratum in: Cancer J. 2005;11(4):354.
  16. Tsunemi Y, Sekiya T, Saeki H, Hirai K, Ohta K, Nakamura K, et al. Lack of association of CCR4 single nucleotide polymorphism with atopic dermatitis in Japanese patients. Acta Derm Venereol. 2004;84(3):187-90. doi: 10.1080/00015550410025859.
  17. Erfani N, Ahrari S, Ahrari I, Hosseini SV. CCR4 C1014T and CCL22 C16A genetic variations in the Iranian patients with colorectal adenocarcinoma. Iran J Allergy Asthma Immunol. 2014;13(6):440-6.
  18. Erfani N, Nedaei Ahmadi AS, Ghayumi MA, Mojtahedi Z. Genetic polymorphisms of CCL22 and CCR4 in patients with lung cancer. Iran J Med Sci. 2014;39(4):367-73.
  19. Berin MC, Dwinell MB, Eckmann L, Kagnoff MF. Production of MDC/CCL22 by human intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2001;280(6):G1217-26. doi: 10.1152/ajpgi.2001.280.6.G1217.
  20. Cao L, Hu X, Zhang J, Huang G, Zhang Y. The role of the CCL22-CCR4 axis in the metastasis of gastric cancer cells into omental milky spots. J Transl Med. 2014;12:267. doi: 10.1186/s12967-014-0267-1.
  21. Karasaki T, Qiang G, Anraku M, Sun Y, Shinozaki-Ushiku A, Sato E, et al. High CCR4 expression in the tumor microenvironment is a poor prognostic indicator in lung adenocarcinoma. J Thorac Dis. 2018;10(8):4741-50. doi: 10.21037/jtd.2018.07.45.
  22. Wang G, Yu D, Tan W, Zhao D, Wu C, Lin D. Genetic polymorphism in chemokine CCL22 and susceptibility to Helicobacter pylori infection‐related gastric carcinoma. Cancer. 2009;115(11):2430-7.
  23. Erfani N, Moghaddasi-Sani F, Razmkhah M, Haghshenas MR, Talei A, Ghaderi A. CCL22 16C/A genetic variation is not associated with breast carcinoma in southern Iranian population. Iran J Immunol. 2012;9(4):226-33.
  24. Excoffier L, Laval G, Schneider S. Arlequin (version 3.0): an integrated software package for population genetics data analysis. Evol Bioinform Online. 2007;1:47-50.
  25. Jafarzadeh A, Fooladseresht H, Minaee K, Bazrafshani MR, Khosravimashizi A, Nemati M, et al. Higher circulating levels of chemokine CCL22 in patients with breast cancer: evaluation of the influences of tumor stage and chemokine gene polymorphism. Tumour Biol. 2015;36(2):1163-71. doi: 10.1007/s13277-014-2739-6.
  26. Hirota T, Saeki H, Tomita K, Tanaka S, Ebe K, Sakashita M, et al. Variants of CC motif chemokine 22 (CCL22) are associated with susceptibility to atopic dermatitis: case-control studies. PLoS One. 2011;6(11):e26987.doi: 10.1371/journal.pone.0026987.
  27. Galimberti D, Scalabrini D, Fenoglio C, De Riz M, Comi C, Venturelli E, et al. Gender-specific influence of the chromosome 16 chemokine gene cluster on the susceptibility to Multiple Sclerosis. J Neurol Sci. 2008;267(1-2):86-90. doi: 10.1016/j.jns.2007.10.001.
  28. Jones D, O'Hara C, Kraus MD, Perez–Atayde AR, Shahsafaei A, Wu L, et al. Expression pattern of T-cell–associated chemokine receptors and their chemokines correlates with specific subtypes of T-cell non-Hodgkin lymphoma. Blood. 2000;96(2):685-90. doi.org/10.1182/blood.V96.2.685.
  29. Lee JH, Cho YS, Lee JY, Kook MC, Park JW, Nam BH, et al. The chemokine receptor CCR4 is expressed and associated with a poor prognosis in patients with gastric cancer. Ann Surg. 2009;249(6):933-41. doi: 10.1097/SLA.0b013e3181a77ccc.