Skip to main content
NCBI home page
Journal of Clinical Laboratory Analysis logoLink to Journal of Clinical Laboratory Analysis
. 2009 Nov 19;23(6):387–393. doi: 10.1002/jcla.20346

CXCL12 rs1801157 polymorphism in patients with breast cancer, hodgkin's lymphoma, and non‐hodgkin's lymphoma

Karen Brajão de Oliveira 1, Julie Massayo Maeda Oda 1, Julio Cesar Voltarelli 2, Thiago Franco Nasser 1, Mario Augusto Ono 1, Thiago Cezar Fujita 1, Tiemi Matsuo 3, Maria Angelica Ehara Watanabe 1,✉
PMCID: PMC6649101  PMID: 19927352

Abstract

Chemokines and their receptors regulate the trafficking of immune cells during their development, inflammation, and tissue repair. The single‐nucleotide polymorphism (SNP) rs1801157 (previously known as CXCL12‐A/ stromal cell‐derived factor‐1 (SDF1)‐3′A) in CXCL12/SDF1 gene was assessed in breast cancer, Hodgkin's lymphoma (HL), and non‐Hodgkin's lymphoma (NHL), since the chemokine CXCL12, previously known as SDF1, and its receptor CXCR4 regulate leukocyte trafficking and many essential biological processes, including tumor growth, angiogenesis, and metastasis of different types of tumors. Genotyping was performed by PCR‐RFLP (polymerase chain reaction followed by restriction fragment length polymorphism) using a restriction enzyme HpaII cleavage. No significant difference was observed in genotype distribution between breast cancer patients (GG: 57.3%; GA: 39.8%; AA: 2.9%) and healthy female controls (GG: 62.9%; GA: 33%; AA: 4.1%) nor between HL patients (GG: 61.1%; GA:27.8%; AA: 11.1%) and healthy controls (GG: 65.6%; GA: 28.9%; AA: 5.5%), whereas a significant difference was observed in genotype distribution between NHL patients (GG: 51.4%; GA: 47.1%; AA: 1.5%) and healthy controls (GG: 65.6%; GA: 28.9%; AA: 5.5%). Further studies will be necessary to elucidate the cancer chemokine network. However, this study suggests that CXCL12 rs1801157 polymorphism may have important implications in the pathogenesis of NHL. J. Clin. Lab. Anal. 23:387–393, 2009. © 2009 Wiley‐Liss, Inc.

Keywords: CXCL12 rs1801157 polymorphism, breast cancer, Hodgkin's lymphoma, non‐Hodgkin's lymphoma, chemokines

REFERENCES

  • 1.Brazil. 2007. Ministry of Health. Secretariat for Health Assistance. National Cancer Institute. Prevention and Surveillance Coordination Unit. Estimate 2008: Brazilian cancer incidence. Rio de Janeiro: NCI, 2007. [http://www.inca.gov.br/estimativa/2008/finalversion.pdf].
  • 2. WHO. World Health Organization . Cancer. Fact Sheet No. 297. 2006. [homepage on the internet]. Geneva: World Health Organization; c2007 [cited 2007. Oct 10]. [http://www.who.int/mediacentre/factsheets/fs297/en/print.html].
  • 3. Luker KE, Luker GD. Functions of CXCL12 and CXCR4 in breast cancer. Cancer Lett 2006;238:30–41. [DOI] [PubMed] [Google Scholar]
  • 4. Golay J, Introna M. Chemokines and antagonists in non‐Hodgkin's lymphoma. Expert Opin Ther Targets 2008;12:621–635. [DOI] [PubMed] [Google Scholar]
  • 5. Koizumi K, Hojo S, Akashi T, Yasumoto K, Saiki I. Chemokine receptors in cancer metastasis and cancer cell‐derived chemokines in host immune response. Cancer Sci 2007;98:1652–1658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Muller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 2001;410:50–56. [DOI] [PubMed] [Google Scholar]
  • 7. Tashiro K, Tada H, Heilker R, Shirozu M, Nakano T, Honjo T. Signal sequence trap: A cloning strategy for secreted proteins and type I membrane proteins. Science 1993;261:600–603. [DOI] [PubMed] [Google Scholar]
  • 8. Nagasawa T, Hirota S, Tachibana K, et al. Defects of B‐cell lymphopoiesis and bone‐marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF‐1. Nature 1996;382:635–638. [DOI] [PubMed] [Google Scholar]
  • 9. Askari AT, Unzek S, Popovic ZB, et al. Effect of stromal‐cell‐derived factor 1 on stem‐cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 2003;362:697–703. [DOI] [PubMed] [Google Scholar]
  • 10. Ratajczak MZ, Majka M, Kucia M, et al. Expression of functional CXCR4 by muscle satellite cells and secretion of SDF‐1 by muscle‐derived fibroblasts is associated with the presence of both muscle progenitors in bone marrow and hematopoietic stem/progenitor cells in muscles. Stem Cells 2003;21:363–371. [DOI] [PubMed] [Google Scholar]
  • 11. Kollet O, Shivtiel S, Chen YQ, et al. HGF, SDF‐1, and MMP‐9 are involved in stress‐induced human CD34+stem cell recruitment to the liver. J Clin Investig 2003;112:160–169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Tachibana K, Hirota S, Iizasa H, et al. The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature 1998;393:591–594. [DOI] [PubMed] [Google Scholar]
  • 13. Schrader AJ, Lechner O, Templin M, et al. CXCR4/CXCL12 expression and signaling in kidney cancer. Br J Cancer 2002;86:1250–1256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. Ponomaryov T, Peled A, Petit I, et al. Induction of the chemokine stromal‐derived factor‐1 following DNA damage improves human stem cell function. J Clin Investig 2000;106:1331–1339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Yun HJ, Jo DY. Production of stromal cell‐derived factor‐1 (SDF‐1) and expression of CXCR4 in human bone marrow endothelial cells. J Korean Med Sci 2003;18:679–685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Ma Q, Jones D, Borghesani PR, et al. Impaired B‐lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4‐ and SDF‐1‐deficient mice. Proc Natl Acad Sci USA 1998;95:9448–9453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Barbieri F, Bajetto A, Porcile C, et al. CXC receptor and chemokine expression in human meningioma: SDF1/CXCR4 signaling activates ERK1/2 and stimulates meningioma cell proliferation. Ann N Y Acad Sci 2006;1090:332–343. [DOI] [PubMed] [Google Scholar]
  • 18. Hattori K, Heissig B, Tashiro K, et al. Plasma elevation of stromal cellderived factor‐1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood 2001;97:3354–3360. [DOI] [PubMed] [Google Scholar]
  • 19. Lane WJ, Dias S, Hattori K, et al. Stromal‐derived factor 1‐induced megakaryocyte migration and platelet production is dependent on matrix metalloproteinases. Blood 2000;96:4152–4159. [PubMed] [Google Scholar]
  • 20. Petit I, Jin D, Rafii S. The SDF‐1‐CXCR4 signaling pathway: A molecular hub modulating neo‐angiogenesis. Trends Immunol 2007;28:299–307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Winkler C, Modi W, Smith MW, et al. Genetic restriction of AIDS pathogenesis by an SDF‐1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC). Science 1998;279:389–393. [DOI] [PubMed] [Google Scholar]
  • 22. Balter M. Chemokine mutation slows progression in pathogenesis by a SDF‐1 chemokine gene variant. Science 1998;118:681–688. [DOI] [PubMed] [Google Scholar]
  • 23. Dubois‐Laforgue D, Hendel H, Caillat‐Zucman S, et al. A common stromal cell‐derived factor‐1 chemokine gene variant is associated with the early onset of type 1 diabetes. Diabetes 2001;50:1211–1213. [DOI] [PubMed] [Google Scholar]
  • 24. Reiche EM, Ehara Watanabe MA, Bonametti AM, et al. The effect of stromal cell‐derived factor 1 (SDF1/CXCL12) genetic polymorphism on HIV‐1 disease progression. Int J Mol Med 2006;18:785–793. [PubMed] [Google Scholar]
  • 25. De Oliveira CE, Cavassin GG, Perim ADEL, et al. Stromal cell‐derived factor‐1 chemokine gene variant in blood donors and chronic myelogenous leukemia patients. J Clin Lab Anal 2007;21:49–54. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Vairaktaris E, Vylliotis A, Spyridonodou S, et al. A DNA polymorphism of stromal‐derived factor‐1 is associated with advanced stages of oral cancer. Anticancer Res 2008;28:271–275. [PubMed] [Google Scholar]
  • 27. Razmkhah M, Doroudchi M, Ghayumi SM, Erfani N, Ghaderi A. Stromal cell‐derived factor‐1 (SDF‐1) gene and susceptibility of Iranian patients with lung cancer. Lung Cancer 2005;49:311–315. [DOI] [PubMed] [Google Scholar]
  • 28. Razmkhah M, Talei AR, Doroudchi M, Khalili‐Azad T, Ghaderi A. Stromal cell‐derived factor‐1 (SDF‐1) alleles and susceptibility to breast carcinoma. Cancer Lett 2005;225:261–266. [DOI] [PubMed] [Google Scholar]
  • 29. Dimberg J, Hugander A, Löfgren S, Wågsäter D. Polymorphism and circulating levels of the chemokine CXCL12 in colorectal cancer patients. Int J Mol Med 2007;19:11–15. [PubMed] [Google Scholar]
  • 30. Kirby LT. DNA Fingerprinting: An Introduction. New York: Stocton Press; 1990. [Google Scholar]
  • 31. Moura‐Gallo CV, Simão TA, Ribeiro FS, Andrada‐Serpa MJ, Cardoso LEB, Mendonça GAS. Mutações no gene TP53 em tumores malignos de mama: associação com fatores de risco e características clínico‐patológicas, inclusive risco de óbito, em pacientes esidentes no Rio de Janeiro. Rev Bras Epidemiol 2004;7:167–175. [Google Scholar]
  • 32. Moraes AB, Zanini RR, Turchiello MS, Riboldi J, Medeiros LR. Estudo da sobrevida de pacientes com câncer de mama atendidas no hospital da Universidade Federal de Santa Maria, Rio Grande do Sul, Brasil. Cad Saúde Pública 2006;22:2219–2228. [DOI] [PubMed] [Google Scholar]
  • 33. Marinho VFZ, Metze K, Sanches FSF, Rocha GFS, Gobbi H. Marcadores moleculares em câncer de mama preditivos de metástases axilares. Rev Assoc Med Bras 2008;54:203–207. [DOI] [PubMed] [Google Scholar]
  • 34. Mauch P, Armitage J, Diehl V, Hoppe R, Weiss L. Hodgkin's Disease. Lippincott: Williams & Wilkins; 1999. [Google Scholar]
  • 35. Vassallo J, Paes RP, Soares FA, et al. Histological classification of 1,025 cases of Hodgkin's lymphoma from the State of São Paulo, Brazil. Sao Paulo Med J 2005;123:134–136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. Ries LAG, Melbert D, Krapcho M, et al (editors). SEER Cancer Statistics Review, 1975–2005, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2005/, based on November 2007 SEER data submission, posted to the SEER web site, 2008.
  • 37. Pracchia LF, Linardi CCG, Buccheri V. Gemcitabine and ifosfamide in the treatment of Hodgkin's lymphoma refractory to or relapsed after multiple therapies. Rev Bras Hematol Hemoter 2007;29:422–424. [Google Scholar]
  • 38. Costa FPS, Pereira FG, Vassalo J, Freitas LLL, Lorand‐Metze I. Diagnosis of non‐Hodgkin's lymphoma combining immunophenotyping and fine needle aspiration. Rev Bras Hematol Hemoter 2005;27:16–20. [Google Scholar]
  • 39. Chang ET, Smedby KE, Zhang SM, et al. Dietary factors and risk of non‐Hodgkin lymphoma in men and women. Cancer Epidemiol Biomarkers Prev 2005;14:512–520. [DOI] [PubMed] [Google Scholar]
  • 40. Arya M, Ahmed H, Silhi N, Williamson M, Patel HR. Clinical importance and therapeutic implications of the pivotal CXCL12–CXCR4 (chemokine ligand‐receptor) interaction in cancer cell migration. Tumour Biol 2007;28:123–131. [DOI] [PubMed] [Google Scholar]
  • 41. Vandercappellen J, Damme JV, Struyf S. The role of CXC chemokines and their receptors in cancer. Cancer Lett 2008;267:226–244. [DOI] [PubMed] [Google Scholar]
  • 42. Bleul CC, Farzan M, Choe H, et al. The lymphocyte chemoattractant SDF‐1 is a ligand for LESTR/fusin and blocks HIV‐1 entry. Nature 1996;382:829–833. [DOI] [PubMed] [Google Scholar]
  • 43. Horuk R. Chemokine receptors. Cytokine Growth Factor Rev 2001;12:313–335. [DOI] [PubMed] [Google Scholar]
  • 44. Burns JM, Summers BC, Wang Y, et al. A novel chemokine receptor for SDF‐1 and I‐TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med 2006;203:2201–2213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45. Libert F, Parmentier M, Lefort A, Dumont JE, Vassart G. Complete nucleotide sequence of a putative G protein coupled receptor: RDC1. Nucleic Acids Res 1990;18:1917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46. Libert F, Passage E, Parmentier M, Simons MJ, Vassart G, Mattei MG. Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor. Genomics 1991;11:225–227. [DOI] [PubMed] [Google Scholar]
  • 47. Phillips RJ, Burdick MD, Lutz M, Belperio JA, Keane MP, Strieter RM. The stromal derived factor‐1/CXCL12‐CXC chemokine receptor 4 biological axis in non‐small cell lung cancer metastases. Am J Respir Crit Care Med 2003;167:1676–1686. [DOI] [PubMed] [Google Scholar]
  • 48. Watanabe MA, De Oliveira Cavassin GG, Orellana MD, et al. SDF‐1 gene polymorphisms and syncytia induction in Brazilian HIV‐1 infected individuals. Microb Pathog 2003;35:31–34. [DOI] [PubMed] [Google Scholar]
  • 49. Zafiropoulos A, Crikas N, Passam AM, Spandidos DA. Significant involvement of CCR2‐64I and CXCL12‐3a in the development of sporadic breast cancer. J Med Genet 2004;41:1–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50. Dobrovolskaia MA, Kozlov SV. Inflammation and cancer: When NF‐kappaB amalgamates the perilous partnership. Curr Cancer Drug Targets 2005;5:325–344. [DOI] [PubMed] [Google Scholar]
  • 51. Bao CH, He QT. Advance of research on SDF‐1/CXCR4 axis and angiogenesis in leukemia—Review. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2008;16:447–451. [PubMed] [Google Scholar]
  • 52. Hassan S, Baccarelli A, Salvucci O, Basik M. Plasma stromal cell‐derived factor‐1: Host derived marker predictive of distant metastasis in breast cancer. Clin Cancer Res 2008;14:446–454. [DOI] [PubMed] [Google Scholar]
  • 53. Wang J, Loberg R, Taichman RS. The pivotal role of CXCL12 (SDF‐1)/CXCR4 axis in bone metastasis. Cancer Metastasis Rev 2006;25:573–587. [DOI] [PubMed] [Google Scholar]
  • 54. Zhang C, Cui GH, Liu F, Wu QL, Chen Y. The role of stromal cell derived factor‐1/CXCR4 biological axis in tumor metastasis of non‐Hodgkin lymphoma. Zhonghua Yi Xue Za Zhi 2007;87:695–697. [PubMed] [Google Scholar]
  • 55. Groves FD, Linet MS, Travis LB, Devesa SS. Cancer surveillance series: Non‐Hodgkin's lymphoma incidence by histologic subtype in the United States from 1978 through 1995. J Natl Cancer Inst 2000;92:1240–1251. [DOI] [PubMed] [Google Scholar]
  • 56. Syed AS, Samad FA, ur Rahman M. Large B cell lymphoma—year by year. J Ayub Med Coll Abbottabad 2007;19:121–126. [PubMed] [Google Scholar]
  • 57. Bosetti C, Levi F, Ferlay J, Lucchini F, Negri E, La Vecchia C. Incidence and mortality from non‐Hodgkin lymphoma in Europe: The end of an epidemic? Int J Cancer 2008;123:1917–1923. [DOI] [PubMed] [Google Scholar]
  • 58. Lapidot T, Kollet O. The essential roles of the chemokine SDF‐1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune‐deficient NOD/SCID and NOD/SCID/B2m (null) mice. Leukemia 2002;16:1992–2003. [DOI] [PubMed] [Google Scholar]
  • 59. Cavassin GGO, De Lucca FL, Delgado André N , et al. Molecular investigation of the stromal cell‐derived factor‐1 chemokine in lymphoid leukemia and lymphoma patients from Brazil. Blood Cells Mol Dis 2004;33:90–93. [DOI] [PubMed] [Google Scholar]
  • 60. Rabkin CS, Yang Q, Goedert JJ, Nguyen G, Mitsuya H, Sei S. Chemokine and chemokine receptor gene variants and risk of non‐Hodgkin's lymphoma in human immunodeficiency virus‐1‐infected individuals. Blood 1999;93:1838–1842. [PubMed] [Google Scholar]
  • 61. Sei S, O'Neill DP, Stewart SK, et al. Increased level of stromal cell‐derived factor‐1 mRNA in peripheral blood mononuclear cells from children with AIDS‐related lymphoma. Cancer Res 2001;61:5028–5037. [PubMed] [Google Scholar]
  • 62. Corcione A, Ottonello L, Tortolina G, et al. Stromal cell‐derived factor‐1 as a chemoattractant for follicular center lymphoma B cells. J Natl Cancer Inst 2000;92:628–635. [DOI] [PubMed] [Google Scholar]
  • 63. Zeng DF, Kong PY, Chen XH, et al. Expression of stromal cell derived factor‐1(SDF‐1) and its receptor CXCR4 in hematologic malignancies. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2005;13:274–277. [PubMed] [Google Scholar]
  • 64. Lin T, Tseng HF, Yang CH, et al. Combinational polymorphisms of seven CXCL12‐related genes are protective against breast cancer in Taiwan. OMICS 2009;13:165–172. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Laboratory Analysis are provided here courtesy of Wiley

RESOURCES