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Breast Cancer Research and Treatment

, Volume 124, Issue 2, pp 453–457 | Cite as

Transforming growth factorβ1 L10P variant plays an active role on the breast cancer susceptibility in Caucasian: evidence from 10,392 cases and 11,697 controls

  • Xiangyu Ma
  • Chunhai Chen
  • Hongyan Xiong
  • Yafei Li
Epidemiology

Abstract

In view of the essential role of Transforming Growth Factorβ1 (TGFB1) on both inhibiting the development of early benign breast tumors as well as promoting tumor invasion, the association of TGFB1 L10P polymorphism and breast cancer risk has been widely reported, but results of previous studies were somewhat contradictory and underpowered. To overcome the limitations of individual study and to understand the real situation, we conducted a systematic review and meta-analysis towards the association between TGFB1 L10P polymorphism and breast cancer. Through retrieving MEDLINE, PubMed, Embase, and Web of Science, a total of 16 studies with 10,392 cases and 11,697 controls were identified. The results showed that significant association was found in the recessive genetic model for Caucasian (OR = 1.152, 95% CI = 1.020–1.301). However, we did not find any associations in additive genetic model (PP vs. LL for total: OR = 1.026, 95% CI = 0.940–1.121), allele contrast (L vs. P for total: OR = 1.004, 95% CI = 0.966–1.044), and dominant genetic model (PP + LP vs. LL for total: OR = 1.001, 95% CI = 0.946–1.061). Conclusively, this meta-analysis strongly suggests that TGFB1 L10P polymorphism may play a low penetrance role in breast cancer susceptibility in Caucasian. Large well-designed epidemiological studies will be necessary to validate the risk identified in the current meta-analysis.

Keywords

TGFB1 Breast cancer Polymorphism Meta-analysis Susceptibility 

Notes

Acknowledgment

This work was not supported by any funds.

References

  1. 1.
    Hsieh YY, Chang CC, Tsai FJ, Peng CT, Yeh LS, Lin CC (2005) Polymorphism for transforming growth factor beta 1–509 (TGF-B1–509): association with endometriosis. Biochem Genet 43:203–210CrossRefPubMedGoogle Scholar
  2. 2.
    Elliott RL, Blobe GC (2005) Role of transforming growth factor Beta in human cancer. J Clin Oncol 23:2078–2093. doi: 10.1200/JCO.2005.02.047 CrossRefPubMedGoogle Scholar
  3. 3.
    Derynck R, Akhurst RJ, Balmain A (2001) TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 29:117–129. doi: 10.1038/ng1001-117ng1001-117 CrossRefPubMedGoogle Scholar
  4. 4.
    Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012. doi: jst00003 CrossRefPubMedGoogle Scholar
  5. 5.
    Little J, Bradley L, Bray MS, Clyne M, Dorman J, Ellsworth DL, Hanson J, Khoury M, Lau J, O’Brien TR, Rothman N, Stroup D, Taioli E, Thomas D, Vainio H, Wacholder S, Weinberg C (2002) Reporting, appraising, and integrating data on genotype prevalence and gene-disease associations. Am J Epidemiol 156:300–310PubMedGoogle Scholar
  6. 6.
    Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748PubMedGoogle Scholar
  7. 7.
    DerSimonian R, Kacker R (2007) Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 28:105–114. doi: 10.1016/j.cct.2006.04.004 CrossRefPubMedGoogle Scholar
  8. 8.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188. doi: 0197-2456(86)90046-2 CrossRefPubMedGoogle Scholar
  9. 9.
    Rajkumar T, Samson M, Rama R, Sridevi V, Mahji U, Swaminathan R, Nancy NK (2008) TGFbeta1 (Leu10Pro), p53 (Arg72Pro) can predict for increased risk for breast cancer in south Indian women and TGFbeta1 Pro (Leu10Pro) allele predicts response to neo-adjuvant chemo-radiotherapy. Breast Cancer Res Treat 112:81–87. doi: 10.1007/s10549-007-9821-3 CrossRefPubMedGoogle Scholar
  10. 10.
    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 7:175. doi: 10.1186/1471-2407-7-175 CrossRefPubMedGoogle Scholar
  11. 11.
    Scola L, Vaglica M, Crivello A, Palmeri L, Forte GI, Macaluso MC, Giacalone A, Di Noto L, Bongiovanni A, Raimondi C, Accardo A, Verna R, Candore G, Caruso C, Lio D, Palmeri S (2006) Cytokine gene polymorphisms and breast cancer susceptibility. Ann N Y Acad Sci 1089:104–109. doi: 10.1196/annals.1386.017 CrossRefPubMedGoogle Scholar
  12. 12.
    Feigelson HS, Patel AV, Diver WR, Stevens VL, Thun MJ, Calle EE (2006) Transforming growth factor beta receptor type I and transforming growth factor beta1 polymorphisms are not associated with postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 15:1236–1237. doi: 10.1158/1055-9965.EPI-06-0163 CrossRefPubMedGoogle Scholar
  13. 13.
    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 14:1567–1570. doi: 10.1158/1055-9965.EPI-05-0078 CrossRefPubMedGoogle Scholar
  14. 14.
    Kaklamani VG, Baddi L, Liu J, Rosman D, Phukan S, Bradley C, Hegarty C, McDaniel B, Rademaker A, Oddoux C, Ostrer H, Michel LS, Huang H, Chen Y, Ahsan H, Offit K, Pasche B (2005) Combined genetic assessment of transforming growth factor-beta signaling pathway variants may predict breast cancer risk. Cancer Res 65:3454–3461. doi: 10.1158/0008-5472.CAN-04-2961 PubMedGoogle Scholar
  15. 15.
    Lee KM, Park SK, Hamajima N, Tajima K, Yoo KY, Shin A, Noh DY, Ahn SH, Hirvonen A, Kang D (2005) Genetic polymorphisms of TGF-beta1 & TNF-beta and breast cancer risk. Breast Cancer Res Treat 90:149–155. doi: 10.1007/s10549-004-3859-2 CrossRefPubMedGoogle Scholar
  16. 16.
    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 112:94–99. doi: 10.1002/ijc.20370 CrossRefPubMedGoogle Scholar
  17. 17.
    Saha A, Gupta V, Bairwa NK, Malhotra D, Bamezai R (2004) Transforming growth factor-beta1 genotype in sporadic breast cancer patients from India: status of enhancer, promoter, 5′-untranslated-region and exon-1 polymorphisms. Eur J Immunogenet 31:37–42. doi: 442 CrossRefPubMedGoogle Scholar
  18. 18.
    Le Marchand L, Haiman CA, van den Berg D, Wilkens LR, Kolonel LN, Henderson BE (2004) T29C polymorphism in the transforming growth factor beta1 gene and postmenopausal breast cancer risk: the Multiethnic Cohort Study. Cancer Epidemiol Biomarkers Prev 13:412–415PubMedGoogle Scholar
  19. 19.
    Krippl P, Langsenlehner U, Renner W, Yazdani-Biuki B, Wolf G, Wascher TC, Paulweber B, Bahadori B, Samonigg H (2003) The L10P polymorphism of the transforming growth factor-beta 1 gene is not associated with breast cancer risk. Cancer Lett 201:181–184. doi: S0304383503004683 CrossRefPubMedGoogle Scholar
  20. 20.
    Hishida A, Iwata H, Hamajima N, Matsuo K, Mizutani M, Iwase T, Miura S, Emi N, Hirose K, Tajima K (2003) Transforming growth factor B1 T29C polymorphism and breast cancer risk in Japanese women. Breast Cancer 10:63–69CrossRefPubMedGoogle Scholar
  21. 21.
    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 factorbeta1 signal peptide variant increases secretion in vitro and is associated with increased incidence of invasive breast cancer. Cancer Res 63:2610–2615PubMedGoogle Scholar
  22. 22.
    Ziv E, Cauley J, Morin PA, Saiz R, Browner WS (2001) Association between the T29 → C polymorphism in the transforming growth factor beta1 gene and breast cancer among elderly white women: the Study of Osteoporotic Fractures. JAMA 285:2859–2863. doi: joc02284 CrossRefPubMedGoogle Scholar
  23. 23.
    Rebbeck TR, Antoniou AC, Llopis TC, Nevanlinna H, Aittomaki K, Simard J, Spurdle AB, Couch FJ, Pereira LH, Greene MH, Andrulis IL, Pasche B, Kaklamani V, Hamann U, Szabo C, Peock S, Cook M, Harrington PA, Donaldson A, Male AM, Gardiner CA, Gregory H, Side LE, Robinson AC, Emmerson L, Ellis I, Peyrat JP, Fournier J, Vennin P, Adenis C, Muller D, Fricker JP, Longy M, Sinilnikova OM, Stoppa-Lyonnet D, Schmutzler RK, Versmold B, Engel C, Meindl A, Kast K, Schaefer D, Froster UG, Chenevix-Trench G, Easton DF (2009) No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a multi-center cohort study. Breast Cancer Res Treat 115:185–192. doi: 10.1007/s10549-008-0064-8 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Xiangyu Ma
    • 1
  • Chunhai Chen
    • 2
  • Hongyan Xiong
    • 1
  • Yafei Li
    • 1
  1. 1.Department of Epidemiology, Faculty of Preventive MedicineThird Military Medical UniversityChongqingChina
  2. 2.Department of Occupational Health, Faculty of Preventive MedicineThird Military Medical UniversityChongqingChina

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