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Association of TGF-β1 -509C/T polymorphisms with breast cancer risk: evidence from an updated meta-analysis

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Tumor Biology

Abstract

Epidemiological studies have evaluated the association between transforming growth factor-β1 (TGF-β1) -509C/T polymorphisms and breast cancer risk. However, the results remain conflicting rather than conclusive. The aim of this study was to comprehensively clarify the association between TGF-β1 -509C/T polymorphisms and breast cancer risk. All relevant studies were searched in the electronic databases. The potential sources of heterogeneity were detected with the chi-square-based Q test. The strength of associations between TGF-β1 -509C/T polymorphisms and breast cancer risk was measured by odds ratio (OR) and 95 % confidence intervals (CI). Publication bias was tested by Begg’s test and Egger’s test. A total of 10 studies including 10,913 cases and 14,187 controls were included in the meta-analysis. Overall, there was no evidence of significant association of TGF-β1 -509C/T polymorphisms with breast cancer risk (TT vs. CC [OR = 0.97, 95 % CI = 0.83–1.14]; CT vs. CC [OR = 1.05, 95 % CI = 0.90–1.22]; TT + CT vs. CC [OR = 0.99, 95 % CI = 0.91–1.08]; T allele vs. C allele [OR = 0.99, 95 % CI = 0.93–1.06]). Similar results were also found in the subgroup analyses by ethnicity and source of control. When stratified by estrogen receptor (ER) status, TT genotype and T allele were associated with a decreased ER-positive breast cancer risk (OR = 0.66, 95 % CI = 0.49–0.90 and OR = 0.85, 95 % CI = 0.75–0.96, respectively). The present meta-analysis results suggest that TGF-β1 -509C/T variants may not contribute to the risk of breast cancer overall. However, T allele may be a potential protective factor for developing ER-positive breast cancer. Well-designed studies with larger sample size were required to verify our findings further.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.

    Article  PubMed  Google Scholar 

  3. Campa D, Kaaks R, Le Marchand L, Haiman CA, Travis RC, Berg CD, et al. Interactions between genetic variants and breast cancer risk factors in the breast and prostate cancer cohort consortium. J Natl Cancer Inst. 2011;103:1252–63.

    Article  PubMed  Google Scholar 

  4. Dumitrescu RG, Cotarla I. Understanding breast cancer risk—where do we stand in 2005? J Cell Mol Med. 2005;9:208–21.

    Article  CAS  PubMed  Google Scholar 

  5. Li J, Humphreys K, Heikkinen T, Aittomaki K, Blomqvist C, Pharoah PD, et al. A combined analysis of genome-wide association studies in breast cancer. Breast Cancer Res Treat. 2011;126:717–27.

    Article  CAS  PubMed  Google Scholar 

  6. McInerney N, Colleran G, Rowan A, Walther A, Barclay E, Spain S, et al. Low penetrance breast cancer predisposition snps are site specific. Breast Cancer Res Treat. 2009;117:151–9.

    Article  PubMed  Google Scholar 

  7. Peng S, Lu B, Ruan W, Zhu Y, Sheng H, Lai M. Genetic polymorphisms and breast cancer risk: evidence from meta-analyses, pooled analyses, and genome-wide association studies. Breast Cancer Res Treat. 2011;127:309–24.

    Article  PubMed  Google Scholar 

  8. Ignotz RA, Massague J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986;261:4337–45.

    CAS  PubMed  Google Scholar 

  9. Mantel PY, Schmidt-Weber CB. Transforming growth factor-beta: recent advances on its role in immune tolerance. Methods Mol Biol. 2011;677:303–38.

    Article  CAS  PubMed  Google Scholar 

  10. Massague J. Tgfbeta in cancer. Cell. 2008;134:215–30.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Amirghofran Z, Jalali SA, Ghaderi A, Hosseini SV. Genetic polymorphism in the transforming growth factor beta1 gene (-509 c/t and -800 g/a) and colorectal cancer. Cancer Genet Cytogenet. 2009;190:21–5.

    Article  CAS  PubMed  Google Scholar 

  12. Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, et al. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet. 1999;8:93–7.

    Article  CAS  PubMed  Google Scholar 

  13. Silverman ES, Palmer LJ, Subramaniam V, Hallock A, Mathew S, Vallone J, et al. Transforming growth factor-beta1 promoter polymorphism c-509t is associated with asthma. Am J Respir Crit Care Med. 2004;169:214–9.

    Article  PubMed  Google Scholar 

  14. Dunning AM, Ellis PD, McBride S, Kirschenlohr HL, Healey CS, Kemp PR, et al. A transforming growth factorbeta1 signal peptide variant increases secretion in vitro and is associated with increased incidence of invasive breast cancer. Cancer Res. 2003;63:2610–5.

    CAS  PubMed  Google Scholar 

  15. Saha A, Gupta V, Bairwa NK, Malhotra D, Bamezai R. 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. 2004;31:37–42.

    Article  CAS  PubMed  Google Scholar 

  16. Vinod C, Jyothy A, Vijay Kumar M, Raghu Raman R, Nallari P, Venkateshwari A. Heterozygosity for tgf beta1 -509c/t polymorphism is associated with risk for breast cancer in south Indian population. Tumour Biol. 2012. doi:10.1007/s13277-012-0516-y.

    PubMed  Google Scholar 

  17. Cox DG, Penney K, Guo Q, Hankinson SE, Hunter DJ. Tgfb1 and tgfbr1 polymorphisms and breast cancer risk in the nurses’ health study. BMC Cancer. 2007;7:175.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Babyshkina N, Malinovskaya E, Stakheyeva M, Volkomorov V, Slonimskaya E, Maximov V, et al. Association of functional -509c > t polymorphism in the tgf-beta1 gene with infiltrating ductal breast carcinoma risk in a Russian Western Siberian population. Cancer Epidemiol. 2011;35:560–3.

    Article  CAS  PubMed  Google Scholar 

  19. Jakubowska A, Gronwald J, Menkiszak J, Gorski B, Huzarski T, Byrski T, et al. Brca1-associated breast and ovarian cancer risks in Poland: no association with commonly studied polymorphisms. Breast Cancer Res Treat. 2010;119:201–11.

    Article  PubMed  Google Scholar 

  20. Jakubowska A, Jaworska K, Cybulski C, Janicka A, Szymanska-Pasternak J, Lener M, et al. Do brca1 modifiers also affect the risk of breast cancer in non-carriers? Eur J Cancer. 2009;45:837–42.

    Article  CAS  PubMed  Google Scholar 

  21. Jin Q, Hemminki K, Grzybowska E, Klaes R, Soderberg M, Zientek H, et al. Polymorphisms and haplotype structures in genes for transforming growth factor beta1 and its receptors in familial and unselected breast cancers. Int J Cancer. 2004;112:94–9.

    Article  CAS  PubMed  Google Scholar 

  22. MARIE-GENICA. Polymorphisms in the brca1 and abcb1 genes modulate menopausal hormone therapy associated breast cancer risk in postmenopausal women. Breast Cancer Res Treat. 2010;120:727–36.

    Article  Google Scholar 

  23. Shin A, Shu XO, Cai Q, Gao YT, Zheng W. Genetic polymorphisms of the transforming growth factor-beta1 gene and breast cancer risk: a possible dual role at different cancer stages. Cancer Epidemiol Biomark Prev. 2005;14:1567–70.

    Article  CAS  Google Scholar 

  24. Huang Y, Hao Y, Li B, Xie J, Qian J, Chao C, et al. Lack of significant association between tgf-beta1-590c/t polymorphism and breast cancer risk: a meta-analysis. Med Oncol. 2011;28:424–8.

    Article  CAS  PubMed  Google Scholar 

  25. Niu W, Qi Y, Gao P, Zhu D. Association of tgfb1–509 c > t polymorphism with breast cancer: evidence from a meta-analysis involving 23,579 subjects. Breast Cancer Res Treat. 2010;124:243–9.

    Article  CAS  PubMed  Google Scholar 

  26. Qi X, Zhang F, Yang X, Fan L, Zhang Y, Chen L, et al. Transforming growth factor-beta1 polymorphisms and breast cancer risk: a meta-analysis based on 27 case-control studies. Breast Cancer Res Treat. 2010;122:273–9.

    Article  CAS  PubMed  Google Scholar 

  27. Woo SU, Park KH, Woo OH, Yang DS, Kim AR, Lee ES, et al. Association of a tgf-beta1 gene -509 c/t polymorphism with breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2010;124:481–5.

    Article  CAS  PubMed  Google Scholar 

  28. Shu XO, Gao YT, Cai Q, Pierce L, Cai H, Ruan ZX, et al. Genetic polymorphisms in the tgf-beta 1 gene and breast cancer survival: a report from the Shanghai breast cancer study. Cancer Res. 2004;64:836–9.

    Article  CAS  PubMed  Google Scholar 

  29. Quarmby S, Fakhoury H, Levine E, Barber J, Wylie J, Hajeer AH, et al. Association of transforming growth factor beta-1 single nucleotide polymorphisms with radiation-induced damage to normal tissues in breast cancer patients. Int J Radiat Biol. 2003;79:137–43.

    Article  CAS  PubMed  Google Scholar 

  30. Scollen S, Luccarini C, Baynes C, Driver K, Humphreys MK, Garcia-Closas M, et al. Tgf-beta signaling pathway and breast cancer susceptibility. Cancer Epidemiol Biomark Prev. 2011;20:1112–9.

    Article  CAS  Google Scholar 

  31. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  CAS  PubMed  Google Scholar 

  32. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  CAS  PubMed  Google Scholar 

  33. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.

    Article  CAS  PubMed  Google Scholar 

  34. Lux MP, Fasching PA, Beckmann MW. Hereditary breast and ovarian cancer: review and future perspectives. J Mol Med (Berl). 2006;84:16–28.

    Article  Google Scholar 

  35. Jin G, Wang L, Chen W, Hu Z, Zhou Y, Tan Y, et al. Variant alleles of tgfb1 and tgfbr2 are associated with a decreased risk of gastric cancer in a chinese population. Int J Cancer. 2007;120:1330–5.

    Article  CAS  PubMed  Google Scholar 

  36. Slattery ML, Herrick JS, Lundgreen A, Wolff RK. Genetic variation in the tgf-beta signaling pathway and colon and rectal cancer risk. Cancer Epidemiol Biomark Prev. 2011;20:57–69.

    Article  CAS  Google Scholar 

  37. Vishnoi M, Pandey SN, Modi DR, Kumar A, Mittal B. Genetic susceptibility of epidermal growth factor +61a > g and transforming growth factor beta1–509c > t gene polymorphisms with gallbladder cancer. Hum Immunol. 2008;69:360–7.

    Article  CAS  PubMed  Google Scholar 

  38. Wei YS, Zhu YH, Du B, Yang ZH, Liang WB, Lv ML, et al. Association of transforming growth factor-beta1 gene polymorphisms with genetic susceptibility to nasopharyngeal carcinoma. Clin Chim Acta. 2007;380:165–9.

    Article  CAS  PubMed  Google Scholar 

  39. Kim YJ, Lee HS, Im JP, Min BH, Kim HD, Jeong JB, et al. Association of transforming growth factor-beta1 gene polymorphisms with a hepatocellular carcinoma risk in patients with chronic hepatitis b virus infection. Exp Mol Med. 2003;35:196–202.

    Article  CAS  PubMed  Google Scholar 

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Funding Statement

This research was supported by National Basic Research Program of China (No. 2012CB518200) and National Nature Science Foundation of China (No. 81272180).

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Authors and Affiliations

  1. Henan Center for Disease Control and Prevention, Zhengzhou, 450016, People’s Republic of China

    Yadong Wang

  2. Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China

    Yadong Wang, Xiaojing Meng & Fei Zou

  3. Department of Nutrition Health, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China

    Xinwei Chu

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  1. Yadong Wang
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Correspondence to Fei Zou.

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Yadong Wang and Xinwei Chu equally contributed to this work.

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Wang, Y., Chu, X., Meng, X. et al. Association of TGF-β1 -509C/T polymorphisms with breast cancer risk: evidence from an updated meta-analysis. Tumor Biol. 35, 935–942 (2014). https://doi.org/10.1007/s13277-013-1122-3

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