Molecular Biology Reports

, Volume 38, Issue 2, pp 1263–1267 | Cite as

CCL2 −2518 A/G single nucleotide polymorphism as a risk factor for breast cancer

  • Łukasz Kruszyna
  • Margarita Lianeri
  • Błażej Rubis
  • Hanna Knuła
  • Maria Rybczyńska
  • Sylwia Grodecka-Gazdecka
  • Paweł P. Jagodziński


The contribution of the CCL2 −2518 A>G (rs 1024611) polymorphism in the occurrence and progression of various cancers has been found to be discordant. We studied the prevalence of the CCL2 −2518 A>G polymorphism in patients with breast cancer (n = 160) and controls (n = 323) in a sample of the Polish population. There were no significant differences in CCL2 −2518 A>G genotypes between patients with breast tumors and controls. Odds ratio (OR) for patients bearing the GG genotype was 1.481 (95% CI = 0.7711–2.845, P = 0.2358), and OR of the GG and AG genotypes was 0.7269 (95% CI = 0.4967–1.064, P = 0.1002). There was also no significant distinction in the prevalence of alleles between patients and healthy individuals. OR for the CCL2 −2518 G allele frequency was 0.8903 (95% CI = 0.6611–1.199, P = 0.4441). Analysis of the association between tumor size, lymph node metastases, histological grade, and distribution of genotypes and alleles for the CCL2 −2518 A>G polymorphism also did not show significant differences. Our results did not show association of the CCL2 −2518 A>G polymorphism with breast cancer occurrence and clinical characteristics in a sample of the Polish cohort.


CCL2 Breast cancer Polymorphism 


  1. 1.
    Parsa P, Parsa B (2009) Effects of reproductive factors on risk of breast cancer: a literature review. Asian Pac J Cancer Prev 10:545–550PubMedGoogle Scholar
  2. 2.
    Pisani P, Bray F, Parkin DM (2002) Estimates of the world-wide prevalence of cancer for 25 sites in the adult population. Int J Cancer 97:72–81CrossRefPubMedGoogle Scholar
  3. 3.
    Vargo-Gogola T, Rosen JM (2007) Modelling breast cancer: one size does not fit all. Nat Rev Cancer 7:659–672CrossRefPubMedGoogle Scholar
  4. 4.
    Dapic V, Carvalho MA, Monteiro AN (2005) Breast cancer susceptibility and the DNA damage response. Cancer Control 12:127–136PubMedGoogle Scholar
  5. 5.
    Veronesi U, Boyle P, Goldhirsch A et al (2005) Breast cancer. Lancet 365:1727–1741CrossRefPubMedGoogle Scholar
  6. 6.
    Bilalović N, Vranić S, Serdarević F et al (2006) The role of the stroma in carcinogenesis. Bosn J Basic Med Sci 6:33–38PubMedGoogle Scholar
  7. 7.
    Mantovani A, Sica A (2010) Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol 22:231–237CrossRefPubMedGoogle Scholar
  8. 8.
    O’Sullivan C, Lewis CE (1994) Tumour -associated leukocytes: friends or foes in breast carcinoma. J Pathol 172:229–235CrossRefPubMedGoogle Scholar
  9. 9.
    Camp BJ, Dyhrman ST, Memoli VA et al (1996) In situ cytokine production by breast cancer tumor-infiltrating lymphocytes. Ann Surg Oncol 13:176–184CrossRefGoogle Scholar
  10. 10.
    Clemente CG, Mihm MC Jr, Bufalino R et al (1996) Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 77:1303–1310CrossRefPubMedGoogle Scholar
  11. 11.
    Nakano O, Sato M, Naito Y et al (2001) Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res 61:5132–5136PubMedGoogle Scholar
  12. 12.
    Furihata M, Ohtsuki Y, Sonobe H et al (1993) Prognostic significance of simultaneous infiltration of HLA-DR-positive dendritic cells and tumor infiltrating lymphocytes into human esophageal carcinoma. Tohoku J Exp Med 169:187–195CrossRefPubMedGoogle Scholar
  13. 13.
    Naito Y, Saito K, Shiiba K et al (1998) CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 58:3491–3494PubMedGoogle Scholar
  14. 14.
    Jass JR (1986) Lymphocytic infiltration and survival in rectal cancer. J Clin Pathol 39:585–589CrossRefPubMedGoogle Scholar
  15. 15.
    Zhang L, Conejo-Garcia JR, Katsaros D et al (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 348:203–213CrossRefPubMedGoogle Scholar
  16. 16.
    Aaltomaa S, Lipponen P, Eskelinen M et al (1992) Lymphocyte infiltrates as a prognostic variable in female breast cancer. Eur J Cancer 28A:859–864CrossRefPubMedGoogle Scholar
  17. 17.
    Menard S, Tomasic G, Casalini P et al (1997) Lymphoid infiltration as a prognostic variable for early-onset breast carcinomas. Clin Cancer Res 3:817–819PubMedGoogle Scholar
  18. 18.
    Charo IF, Taubman MB (2004) Chemokines in the pathogenesis of vascular disease. Circ Res 95:858–866CrossRefPubMedGoogle Scholar
  19. 19.
    Soria G, Ben-Baruch A (2008) The inflammatory chemokines CCL2 and CCL5 in breast cancer. Cancer Lett 267:271–285CrossRefPubMedGoogle Scholar
  20. 20.
    Rovin BH, Lu L, Saxena R (1999) A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression. Biochem Biophys Res Commun 259:344–348CrossRefPubMedGoogle Scholar
  21. 21.
    Fenoglio C, Galimberti D, Lovati C et al (2004) MCP-1 in Alzheimer’s disease patients: A-2518G polymorphism and serum levels. Neurobiol Aging 25:1169–1173CrossRefPubMedGoogle Scholar
  22. 22.
    Ghilardi G, Biondi ML, La Torre A et al (2005) Breast cancer progression and host polymorphisms in the chemokine system: role of the macrophage chemoattractant protein-1 (MCP-1) −2518 G allele. Clin Chem 51:452–455CrossRefPubMedGoogle Scholar
  23. 23.
    Nahon P, Sutton A, Rufat P et al (2007) Lack of association of some chemokine system polymorphisms with the risks of death and hepatocellular carcinoma occurrence in patients with alcoholic cirrhosis: a prospective study. Eur J Gastroenterol Hepatol 19:425–431CrossRefPubMedGoogle Scholar
  24. 24.
    Nahon P, Sutton A, Rufat P et al (2008) Chemokine system polymorphisms, survival and hepatocellular carcinoma occurrence in patients with hepatitis C virus-related cirrhosis. World J Gastroenterol 14:713–719CrossRefPubMedGoogle Scholar
  25. 25.
    Sáenz-López P, Carretero R, Cózar JM et al (2008) Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with prostate cancer. BMC Cancer 8:382CrossRefPubMedGoogle Scholar
  26. 26.
    Attar R, Agachan B, Kuran SB et al (2010) Association of CCL2 and CCR2 gene variants with endometrial cancer in Turkish women. In Vivo 24:243–248PubMedGoogle Scholar
  27. 27.
    Vázquez-Lavista LG, Lima G, Gabilondo F et al (2009) Genetic association of monocyte chemoattractant protein 1 (MCP-1)-2518 polymorphism in Mexican patients with transitional cell carcinoma of the bladder. Urology 74:414–418CrossRefPubMedGoogle Scholar
  28. 28.
    Tse KP, Tsang NM, Chen KD et al (2007) MCP-1 promoter polymorphism at 2518 is associated with metastasis of nasopharyngeal carcinoma after treatment. Clin Cancer Res 13:6320–6326CrossRefPubMedGoogle Scholar
  29. 29.
    HF Frierson Jr, Wolber RA, Berean KW et al (1995) Interobserver reproducibility of the Nottingham modification of the Bloom and Richardson histologic grading scheme for infiltrating ductal carcinoma. Am J Clin Pathol 103:195–198Google Scholar
  30. 30.
    Sobin LH, Wittekind C (1997) TNM: classification of malignant tumors, 5th edn. Wiley-Liss, New YorkGoogle Scholar
  31. 31.
    Huang CS, Chern HD, Chang KJ et al (1999) Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility. Cancer Res 59:4870–4875PubMedGoogle Scholar
  32. 32.
    Kim S, Hagemann A, DeMichele A (2009) Immuno-modulatory gene polymorphisms and outcome in breast and ovarian cancer. Immunol Investig 38:324–340CrossRefGoogle Scholar
  33. 33.
    Carpi A, Nicolini A, Antonelli A et al (2009) Cytokines in the management of high risk or advanced breast cancer: an update and expectation. Curr Cancer Drug Targets 9:888–903CrossRefPubMedGoogle Scholar
  34. 34.
    Ali S, Lazennec G (2007) Chemokines: novel targets for breast cancer metastasis. Cancer Metastasis Rev 26:401–420CrossRefPubMedGoogle Scholar
  35. 35.
    Valković T, Lucin K, Krstulja M et al (1998) Expression of monocyte chemotactic protein-1 in human invasive ductal breast cancer. Pathol Res Pract 194:335–340PubMedGoogle Scholar
  36. 36.
    Goede V, Brogelli L, Ziche M et al (1999) Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1. Int J Cancer 82:765–770CrossRefPubMedGoogle Scholar
  37. 37.
    Ueno T, Toi M, Saji H et al (2000) Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. Clin Cancer Res 6:3282–3289PubMedGoogle Scholar
  38. 38.
    Saji H, Koike M, Yamori T et al (2001) Significant correlation of monocyte chemoattractant protein-1 expression with neovascularization and progression of breast carcinoma. Cancer 92:1085–1091CrossRefPubMedGoogle Scholar
  39. 39.
    Lebrecht A, Grimm C, Lantzsch T et al (2004) Monocyte chemoattractant protein-1 serum levels in patients with breast cancer. Tumour Biol 25:14–17CrossRefPubMedGoogle Scholar
  40. 40.
    Fujimoto H, Sangai T, Ishii G et al (2009) Stromal MCP-1 in mammary tumors induces tumor-associated macrophage infiltration and contributes to tumor progression. Int J Cancer 125:1276–1284CrossRefPubMedGoogle Scholar
  41. 41.
    Mestdagt M, Polette M, Buttice G et al (2006) Transactivation of MCP-1/CCL2 by beta-catenin/TCF-4 in human breast cancer cells. Int J Cancer 118:35–42CrossRefPubMedGoogle Scholar
  42. 42.
    Takahashi M, Miyazaki H, Furihata M et al (2009) Chemokine CCL2/MCP-1 negatively regulates metastasis in a highly bone marrow-metastatic mouse breast cancer model. Clin Exp Metastasis 26:817–828CrossRefPubMedGoogle Scholar
  43. 43.
    Valković T, Fuckar D, Stifter S et al (2005) Macrophage level is not affected by monocyte chemotactic protein-1 in invasive ductal breast carcinoma. J Cancer Res Clin Oncol 131:453–458CrossRefPubMedGoogle Scholar
  44. 44.
    Galvan A, Ioannidis JP, Dragani TA (2010) Beyond genome-wide association studies: genetic heterogeneity and individual predisposition to cancer. Trends Genet 26:132–141CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Łukasz Kruszyna
    • 1
  • Margarita Lianeri
    • 1
  • Błażej Rubis
    • 1
    • 2
  • Hanna Knuła
    • 2
  • Maria Rybczyńska
    • 2
  • Sylwia Grodecka-Gazdecka
    • 3
  • Paweł P. Jagodziński
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyPoznań University of Medical SciencesPoznańPoland
  2. 2.Department of Clinical Chemistry and Molecular DiagnosticsPoznań University of Medical SciencesPoznańPoland
  3. 3.Department of Oncological Surgery, Department of OncologyPoznań University of Medical SciencesPoznańPoland

Personalised recommendations