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Breast Cancer Research and Treatment

, Volume 124, Issue 2, pp 481–485 | Cite as

Association of a TGF-β1 gene −509 C/T polymorphism with breast cancer risk: a meta-analysis

  • Sang Uk Woo
  • Kyong Hwa Park
  • Ok Hee Woo
  • Dae Sik Yang
  • Ae-Ree Kim
  • Eun Sook Lee
  • Jae-Bok Lee
  • Yeul Hong Kim
  • Jun Suk Kim
  • Jae Hong Seo
Epidemiology

Abstract

Transforming growth factor-β1 (TGF-β1) is negative regulator of cell proliferation and the cell cycle, and plasma levels of TGF-β1 are twice as high in TGF-β1 −509 T homozygotes as in −509 C homozygotes. Published studies on the association between the TGF-β1 gene −509 C/T polymorphism and breast cancer risk are inconclusive, and a meta-analysis is required to verify the association. We performed a meta-analysis of four studies, including a total of 5,986 cases and 6,829 controls. Our pooled results indicate that the TGF-β1 gene −509 C/T polymorphism is not associated with breast cancer risk in a TT versus CC codominant (OR = 1.08; 95% CI = 0.87–1.34; P = 0.494), in a CT versus CC codominant (OR = 1.02; 95% CI = 0.94–1.10; P = 0.686), recessive (OR = 0.92; 95% CI = 0.83–1.03; P = 0.157), and dominant (OR = 1.03; 95% CI = 0.96–1.11; P = 0.439) models. Conclusively, this meta-analysis suggests that the TGF-β1 gene −509 T allele polymorphism does not decrease breast cancer risk.

Keywords

TGF-β1 −509 C/T polymorphism Breast cancer risk Meta-analysis 

References

  1. 1.
    Bray F, McCarron P, Parkin DM (2004) The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res 6:229–239CrossRefPubMedGoogle Scholar
  2. 2.
    Janda E, Lehmann K, Killisch I, Jechlinger M, Herzig M, Downward J, Beug H, Grunert S (2002) Ras and TGF[beta] cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways. J Cell Biol 156:299–313CrossRefPubMedGoogle Scholar
  3. 3.
    Rosfjord EC, Dickson RB (1999) Growth factors, apoptosis, and survival of mammary epithelial cells. J Mammary Gland Biol Neoplasia 4:229–237CrossRefPubMedGoogle Scholar
  4. 4.
    Awad MR, El-Gamel A, Hasleton P, Turner DM, Sinnott PJ, Hutchinson IV (1998) Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. Transplantation 66:1014–1020CrossRefPubMedGoogle Scholar
  5. 5.
    Blobe GC, Schiemann WP, Lodish HF (2000) Role of transforming growth factor beta in human disease. N Engl J Med 342:1350–1358CrossRefPubMedGoogle Scholar
  6. 6.
    Letterio JJ, Roberts AB (1998) Regulation of immune responses by TGF-beta. Annu Rev Immunol 16:137–161CrossRefPubMedGoogle Scholar
  7. 7.
    Haukim N, Bidwell JL, Smith AJ, Keen LJ, Gallagher G, Kimberly R, Huizinga T, McDermott MF, Oksenberg J, McNicholl J, Pociot F, Hardt C, D’Alfonso S (2002) Cytokine gene polymorphism in human disease: on-line databases, supplement 2. Genes Immun 3:313–330CrossRefPubMedGoogle Scholar
  8. 8.
    Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, Carter ND, Spector TD (1999) Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet 8:93–97CrossRefPubMedGoogle Scholar
  9. 9.
    Cox DG, Penney K, Guo Q, Hankinson SE, Hunter DJ (2007) TGFB1 and TGFBR1 polymorphisms and breast cancer risk in the Nurses’ Health Study. BMC Cancer 7:175CrossRefPubMedGoogle Scholar
  10. 10.
    Dunning AM, Ellis PD, McBride S, Kirschenlohr HL, Healey CS, Kemp PR, Luben RN, Chang-Claude J, Mannermaa A, Kataja V, Pharoah PD, Easton DF, Ponder BA, Metcalfe JC (2003) A transforming growth factor beta1 signal peptide variant increases secretion in vitro and is associated with increased incidence of invasive breast cancer. Cancer Res 63:2610–2615PubMedGoogle Scholar
  11. 11.
    Jin Q, Hemminki K, Grzybowska E, Klaes R, Soderberg M, Zientek H, Rogozinska-Szczepka J, Utracka-Hutka B, Pamula J, Pekala W, Forsti A (2004) Polymorphisms and haplotype structures in genes for transforming growth factor beta1 and its receptors in familial and unselected breast cancers. Int J Cancer 112:94–99CrossRefPubMedGoogle Scholar
  12. 12.
    Shin A, Shu XO, Cai Q, Gao YT, Zheng W (2005) Genetic polymorphisms of the transforming growth factor-beta1 gene and breast cancer risk: a possible dual role at different cancer stages. Cancer Epidemiol Biomarkers Prev 14:1567–1570CrossRefPubMedGoogle Scholar
  13. 13.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188CrossRefPubMedGoogle Scholar
  14. 14.
    Attisano L, Wrana JL (2002) Signal transduction by the TGF-beta superfamily. Science 296:1646–1647CrossRefPubMedGoogle Scholar
  15. 15.
    Piek E, Heldin CH, Ten Dijke P (1999) Specificity, diversity, and regulation in TGF-beta superfamily signaling. FASEB J 13:2105–2124PubMedGoogle Scholar
  16. 16.
    Shi Y, Massague J (2003) Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113:685–700CrossRefPubMedGoogle Scholar
  17. 17.
    Mulder KM (2000) Role of Ras and Mapks in TGFbeta signaling. Cytokine Growth Factor Rev 11:23–35CrossRefPubMedGoogle Scholar
  18. 18.
    Yamaguchi K, Shirakabe K, Shibuya H, Irie K, Oishi I, Ueno N, Taniguchi T, Nishida E, Matsumoto K (1995) Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction. Science 270:2008–2011CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Sang Uk Woo
    • 1
  • Kyong Hwa Park
    • 2
  • Ok Hee Woo
    • 3
  • Dae Sik Yang
    • 4
  • Ae-Ree Kim
    • 5
  • Eun Sook Lee
    • 1
  • Jae-Bok Lee
    • 1
  • Yeul Hong Kim
    • 2
  • Jun Suk Kim
    • 2
  • Jae Hong Seo
    • 2
  1. 1.Department of SurgeryKorea University Guro HospitalSeoulKorea
  2. 2.Division of Medical Oncology, Department of Internal MedicineKorea University Guro HospitalSeoulKorea
  3. 3.Department of Diagnostic RadiologyKorea University Guro HospitalSeoulKorea
  4. 4.Department of Radiation OncologyKorea University Guro HospitalSeoulKorea
  5. 5.Department of PathologyKorea University Guro HospitalSeoulKorea

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