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Relationships of Single Nucleotide Polymorphisms of Monocyte Chemoattractant Protein 1 and Chemokine Receptor 2 With Susceptibility and Clinicopathologic Characteristics of Neoplasia of Uterine Cervix in Taiwan Women

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Abstract

Few studies reported the implication of single nucleotide polymorphisms (SNPs) of monocyte chemoattractant protein 1 (MCP-1) and its receptor chemokine receptor 2 (CCR-2) in clinical significance of cancer of uterine cervix. We hypothesized that SNPs of MCP-1 and CCR-2 may affect the expression of these genes and then proteins. Therefore, we investigated the influence of the gene polymorphisms of MCP-1 and CCR-2 on the susceptibility and clinicopathologic characteristics of cervical neoplasia in Taiwan women. We recruited 86 patients with invasive cancer and 61 with high-grade dysplasia and 253 control women and selected 1 MCP-1 SNP rs1024611 (−2518G/A) and 1 CCR-2 SNP rs1799864 (190G/A; V64I) to determine their genotypes distribution using polymerase chain reaction-restriction fragment length polymorphism. In comparison to normal individuals with homozygotes GG in MCP-2 SNP, women with GA or AA carried a 2.01 odds ratio of developing cervical cancer. Nevertheless, it was not demonstrated in CCR-2 SNP. Furthermore, women with mutant homozygote (AA) of MCP-1 SNP increased the risk of deep stromal invasion, large tumor diameter, and parametrium invasion of cervical cancer, when compared to those with wild homozygote GG or heterozygote GA. However, women with mutant homozygotes (AA) of CCR-2 SNP did not increase the risk of poor clinicopathologic characteristics. In conclusion, MCP-1 SNP may be correlated with the development, deep stromal invasion, large tumor diameter, and parametrium invasion of cervical cancer but not with cancer recurrence or survival of Taiwan women patients with cancer. However, the SNP of its receptor, CCR-2, is not implicated in cervical cancer.

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References

  1. Nasiell K, Roger V, Nasiell M. Behavior of mild cervical dysplasia during long term follow-up. Obstet Gynecol. 1986;67(5):665–669.

    Article  CAS  PubMed  Google Scholar 

  2. Petignat P, Roy M. Diagnosis and management of cervical cancer. Br Med J. 2007;335(7623):765–768.

    Article  Google Scholar 

  3. Pinto AP, Crum CP. Natural history of cervical neoplasia: defining progression and its consequence. Clin Obstet Gynecol. 2000; 43(2):352–362.

    Article  CAS  PubMed  Google Scholar 

  4. Valente AJ, Graves DT, Vialle-Valentin CE, Delgado R, Schwartz CJ. Purification of a monocyte chemotactic factor secreted by nonhuman primate vascular cells in culture. Biochemistry. 1988;27(11):4162–4168.

    Article  CAS  PubMed  Google Scholar 

  5. Matsushima K, Larsen CG, DuBois GC, Oppenheim JJ. Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line. J Exp Med. 1989;169(4):1485–1490.

    Article  CAS  PubMed  Google Scholar 

  6. Rovin BH, Lu L, Saxena R. A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression. Biochem Biophys Res Commun. 1999;259(2):344–348.

    Article  CAS  PubMed  Google Scholar 

  7. Craig MJ, Loberg RD. CCL2 (monocyte chemoattractant protein-1) in cancer bone metastases. Cancer Metastasis Rev. 2006;25(4): 611–619.

    Article  CAS  PubMed  Google Scholar 

  8. Booth G, Newham P, Barlow R, Raines S, Zheng B, Han S. Gene expression profiles at different stages of collagen-induced arthritis. Autoimmunity. 2008;41(7):512–521.

    Article  CAS  PubMed  Google Scholar 

  9. Takahashi M, Galligan C, Tessarollo L, Yoshimura. Monocyte chemoattractant protein-1 (MCP-1), not MCP-3, is the primary chemokine required for monocyte recruitment in mouse peritonitis induced with thioglycollate or zymosan A. J Immunol. 2009; 183(5):3463–3471.

    Article  CAS  PubMed  Google Scholar 

  10. Charo IF, Taubman MB. Chemokines in the pathogenesis of vascular disease. Circ Res. 2004;95(9):858–866.

    Article  CAS  PubMed  Google Scholar 

  11. Riethdorf L, Riethdorf S, Gützlaff K, Prall F, Löning T. Differential expression of the monocyte chemoattractant protein-1 gene in human apillomavirus-16-infected squamous intraepithelial lesions and squamous cell carcinomas of the cervix uteri. Am J Pathol. 1996;149(5):1469–1476.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Arenberg DA, Keane MP, DiGiovine B, et al. Macrophage infiltration in human non-small-cell lung cancer: the role of CC chemokines. Cancer Immunol Immunother. 2000;49(2):63–70.

    Article  CAS  PubMed  Google Scholar 

  13. Ueno T, Toi M, Saji H, et al. Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. Clin Cancer Res. 2000; 6(8):3282–3289.

    CAS  PubMed  Google Scholar 

  14. Smith MW, Carrington M, Winkler C, et al. CCR2 chemokine receptor and AIDS progression. Nat Med. 1997;3(10):1052–1053.

    Article  CAS  PubMed  Google Scholar 

  15. Kurihara T, Warr G, Loy J, Bravo R. Defects in macrophage recruitment and host defense in mice lacking the CCR2 chemokine receptor. J Exp Med. 1997;186(10):1757–1762.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. MacKay CR. Chemokines: immunology’s high impact factors. Nat Immunol. 2001;2(2):95–101.

    Article  CAS  PubMed  Google Scholar 

  17. Negus RP, Stamp GW, Relf MG, et al. The detection and localization of monocyte chemoattractant protein-1 (MCP-1) in human ovarian cancer. J Clin Invest. 1995;95(5):2391–2396.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Valkovic T, Lucin K, Krstulja M, Dobi-Babic R, Jonjic N. Expression of monocyte chemotactic protein-1 in human invasive ductal breast cancer. Pathol Res Pract. 1998;194(5):335–340.

    Article  CAS  PubMed  Google Scholar 

  19. Liss C, Fekete MJ, Hasina R, Lam CD, Lingen MW. Paracrine angiogenic loop between head-and-neck squamous-cell carcinomas and macrophages. Int J Cancer. 2001;93(6):781–785.

    Article  CAS  PubMed  Google Scholar 

  20. Strauss L, Volland D, Guerrero A, Reichert T. Antiangiogenic and anti-immunosuppressive therapeutic strategies in human head and neck squamous cell carcinoma (HNSCC). Mund Kiefer Gesichtschir. 2005;9(5):273–281.

    Article  CAS  PubMed  Google Scholar 

  21. Kleine-Lowinski K, Gillitzer R, Kuhne-Heid R. Monocytechemo-attractant-protein-1 (MCP-1)-gene expression in cervical intra-epithelial neoplasias and cervical carcinomas. Int J Cancer. 1999;82(1):6–11.

    Article  CAS  PubMed  Google Scholar 

  22. Enjuanes A, Benavente Y, Bosch F, et al. Genetic variants in apoptosis and immunoregulation-related genes are associated with risk of chronic lymphocytic leukemia. Cancer Res. 2008; 68(24):10178–10186.

    Article  CAS  PubMed  Google Scholar 

  23. Vazquez-Lavista LG, Lima G, Gabilondo F, Llorente L. Genetic association of monocyte chemoattractant protein 1 (MCP-1)–2518 polymorphism in Mexican patients with transitional cell carcinoma of the bladder. Urology. 2009;74(2):414–418.

    Article  PubMed  Google Scholar 

  24. Chen MK, Yeh KT, Chiou HL, Lin CW, Chung TT, Yang SF. CCR2-64I gene polymorphism increase susceptibility to oral cancer. Oral Oncol. 2011;47(7):577–582.

    Article  CAS  PubMed  Google Scholar 

  25. Coelho A, Matos A, Catarino R, et al. Protective role of the polymorphism CCR2-64I in the progression from squamous intraepithelial lesions to invasive cervical carcinoma. Gynecol Oncol. 2005;96(3):760–764.

    Article  CAS  PubMed  Google Scholar 

  26. Ivansson EL, Gustavsson IM, Magnusson JJ, et al. Variants of chemokine receptor 2 and interleukin 4 receptor, but not interleukin 10 or Fas ligand, increase risk of cervical cancer. Int J Cancer. 2007;121(11):2451–2457.

    Article  CAS  PubMed  Google Scholar 

  27. Michiels K, Schutyser E, Conings R, et al. Carcinoma cell-derived chemokines and their presence in oral fluid. Eur J Oral Sci. 2009;117(4):362–368.

    Article  CAS  PubMed  Google Scholar 

  28. Koide N, Nishio A, Sato T, Sugiyama A, Miyagawa S. Significance of macrophage chemoattractant protein-1 expression and macrophage infiltration in squamous cell carcinoma of the esophagus. Am J Gastroenterol. 2004;99(9):1667–1674.

    Article  CAS  PubMed  Google Scholar 

  29. Marcus B, Arenberg D, Lee J, et al. Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma. Cancer. 2004; 101(12):2779–2787.

    Article  PubMed  Google Scholar 

  30. Strieter RM, Burdick MD, Gomperts BN, Belperio JA, Keane MP. CXC chemokines in angiogenesis. Cytokine Growth Factor Rev. 2005;16(6):593–609.

    Article  CAS  PubMed  Google Scholar 

  31. Coelho A, Matos A, Catarino R, et al. The influence of chemokine receptor CCR2 genotypes in the route to cervical carcinogenesis. Gynecol Obstet Invest. 2007;64(4):208–212.

    Article  CAS  PubMed  Google Scholar 

  32. Chatterjee K, Dandara C, Hoffman M, Williamson AL. CCR2-V64I polymorphism is associated with increased risk of cervical cancer but not with HPV infection or pre-cancerous lesions in African women. BMC Cancer. 2010;10:278.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Wong LM, Myers SJ, Tsou CL, Gosling J, Arai H, Charo IF. Organization and differential expression of the human monocyte chemoattractant protein 1 receptor gene. Evidence for the role of the carboxyl-terminal tail in receptor trafficking. J Biol Chem. 1997;272(2):1038–1045.

    Article  CAS  PubMed  Google Scholar 

  34. Kostrikis LG, Huang Y, Moore JP, et al. A chemokine receptor CCR2 allele delays HIV-1 disease progression and is associated with a CCR5 promoter mutation. Nat Med. 1998;4(3): 350–353.

    Article  CAS  PubMed  Google Scholar 

  35. Nakayama EE, Tanaka Y, Nagai Y, Iwamoto A, Shioda T. A CCR2–V64I polymorphism affects stability of CCR2A isoform. AIDS. 2004;18(5):729–738.

    Article  CAS  PubMed  Google Scholar 

  36. Sanders SK, Crean SM, Boxer PA, Kellner D, LaRosa GJ, Hunt SW 3rd. Functional differences between monocyte chemotactic protein-1 receptor A and monocyte chemotactic protein-1 receptor B expressed in a Jurkat T cell. J Immunol. 2000;165(9): 4877–4883.

    Article  CAS  PubMed  Google Scholar 

  37. Zheng B, Wiklund F, Gharizadeh B, et al. Genetic polymorphism of chemokine receptors CCR2 and CCR5 in Swedish cervical cancer patients. Anticancer Res. 2006;26(5B):3669–3674.

    CAS  PubMed  Google Scholar 

  38. Gonzalez E, Rovin BH, Sen L, et al. HIV-1infection and AIDS dementia are influenced by a mutant MCP-1 allele linked to increased monocyte infiltration of tissues and MCP-1 levels. Proc Natl Acad Sci U S A. 2002;99(21):13795–13800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Tse KP, Tsang NM, Chen KD, et al. MCP-1 promoter polymorphism at 2518 is associated with metastasis of nasopharyngeal carcinoma after treatment. Clin Cancer Res. 2007;13(21): 6320–6326.

    Article  CAS  PubMed  Google Scholar 

  40. Zhang J, Patel L, Pienta KJ. CC chemokine ligand 2 (CCL2) promotes prostate cancer tumorigenesis and metastasis. Cytokine Growth Factor Rev. 2010;21(1):41–48.

    Article  CAS  PubMed  Google Scholar 

  41. Vicari AP, Caux C. Chemokines in cancer. Cytokine Growth Factor Rev. 2002;13(2):143–154.

    Article  CAS  PubMed  Google Scholar 

  42. Tang CH, Tsai CC. CCL2 increases MMP-9 expression and cell motility in human chondrosarcoma cells via the Ras/Raf/MEK/ERK/NF-κB signaling pathway. Biochem Pharmacol. 2012; 83(3):335–344.

    Article  CAS  PubMed  Google Scholar 

  43. Hussain A, Harish G, Prabhu SA, et al. Inhibitory effect of genistein on the invasive potential of human cervical cancer cells via modulation of matrix metalloproteinase-9 and tissue inhibitors of matrix metalloproteinase-1 expression. Cancer Epidemiol. 2012;36(6):e387–e393.

    Article  CAS  PubMed  Google Scholar 

  44. Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002;2(3):161–174.

    Article  CAS  PubMed  Google Scholar 

  45. Scherer RL, McIntyre JO, Matrisian LM. Imaging matrix metalloproteinases in cancer. Cancer Metastasis Rev. 2008;27(4):679–690.

    Article  PubMed  Google Scholar 

  46. Chiu HY, Sun KH, Chen SY, et al. Autocrine CCL2 promotes cell migration and invasion via PKC activation and tyrosine phosphorylation of paxillin in bladder cancer cells. Cytokine. 2012;59(2): 423–432.

    Article  CAS  PubMed  Google Scholar 

  47. Tabara Y, Kohara K, Yamamoto Y, et al. Polymorphism of the monocyte chemoattractant protein (MCP-1) gene is associated with the plasma level of MCP-1 but not with carotid intima-media thickness. Hypertens Res. 2003;26(9):677–683.

    Article  CAS  PubMed  Google Scholar 

  48. Kucukgergin C, Isman FK, Cakmakoglu B, Sanli O, Seckin S. Association of polymorphisms in MCP-1, CCR2, and CCR5 genes with the risk and clinicopathological characteristics of prostate cancer. DNA Cell Biol. 2012;31(8):1418–1424.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan

    Hsin-Hung Wu MD

  2. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Hsin-Hung Wu MD, Tsung-Hsien Lee MD, PhD, Yi-Torng Tee MD, PhD, Shiuan-Chih Chen MD, PhD, Shun-Fa Yang PhD, Jiunn-Liang Ko PhD & Po-Hui Wang MD, PhD

  3. School of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Tsung-Hsien Lee MD, PhD, Yi-Torng Tee MD, PhD, Shiuan-Chih Chen MD, PhD & Po-Hui Wang MD, PhD

  4. Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan

    Tsung-Hsien Lee MD, PhD, Yi-Torng Tee MD, PhD & Po-Hui Wang MD, PhD

  5. Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taiwan

    Shiuan-Chih Chen MD, PhD

  6. Department of Medical Research, Chung Shan Medical University Hospital, Taiwan

    Shun-Fa Yang PhD

  7. College of Nursing, Chung Shan Medical University, Taichung, Taiwan

    Shu-Kuei Lee MD

  8. Department of Nursing, Chung Shan Medical University Hospital, Taichung, Taiwan

    Shu-Kuei Lee MD

  9. Institute of Nursing, Chung Shan Medical University, Taichung, Taiwan

    Shu-Kuei Lee MD

  10. Department of Obstetrics and Gynecology, Institute of Medicine and School of Medicine, Chung Shan Medical University, Chung Shan Medical University Hospital, 110, Section 1, Chien-Kuo North Road, Taichung, 40201, Taiwan

    Po-Hui Wang MD, PhD

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  1. Hsin-Hung Wu MD
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Correspondence to Po-Hui Wang MD, PhD.

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Wu, HH., Lee, TH., Tee, YT. et al. Relationships of Single Nucleotide Polymorphisms of Monocyte Chemoattractant Protein 1 and Chemokine Receptor 2 With Susceptibility and Clinicopathologic Characteristics of Neoplasia of Uterine Cervix in Taiwan Women. Reprod. Sci. 20, 1175–1183 (2013). https://doi.org/10.1177/1933719113477481

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