TGF-β1 genotype and phenotype in breast cancer and their associations with IGFs and patient survival

L. Mu, D. Katsaros, L. Lu, M. Preti, A. Durando, R. Arisio, H. Yu

Research output: Contribution to journalArticlepeer-review

Abstract

Transforming growth factor-β (TGF-β)-mediated signals play complicated roles in the development and progression of breast tumour. The purposes of this study were to analyse the genotype of TGF-β1 at T29C and TGF-β1 phenotype in breast tumours, and to evaluate their associations with IGFs and clinical characteristics of breast cancer. Fresh tumour samples were collected from 348 breast cancer patients. TGF-β1 genotype and phenotype were analysed with TaqMan® and ELISA, respectively. Members of the IGF family in tumour tissue were measured with ELISA. Cox proportional hazards regression analysis was performed to assess the association of TGF-β1 and disease outcomes. Patients with the T/T (29%) genotype at T29C had the highest TGF-β1, 707.9 pg mg-1, followed by the T/C (49%), 657.8 pg mg-1, and C/C (22%) genotypes, 640.8 pg mg-1, (P=0.210, T/T vs C/C and C/T). TGF-β1 concentrations were positively correlated with levels of oestrogen receptor, IGF-I, IGF-II and IGFBP-3. Survival analysis showed TGF-β1 associated with disease progression, but the association differed by disease stage. For early-stage disease, patients with the T/T genotype or high TGF-β1 had shorter overall survival compared to those without T/T or with low TGF-β1; the hazard ratios (HR) were 3.54 (95% CI: 1.21-10.40) for genotype and 2.54 (95% CI: 1.10-5.89) for phenotype after adjusting for age, grade, histotype and receptor status. For late-stage disease, however, the association was different. The T/T genotype was associated with lower risk of disease recurrence (HR=0.13, 95% CI: 0.02-1.00), whereas no association was found between TGF-β1 phenotype and survival outcomes. The study suggests a complex role of TGF-β1 in breast cancer progression, which supports the finding of in vitro studies that TGF-β1 has conflicting effects on tumour growth and metastasis.

Original languageEnglish
Pages (from-to)1357-1363
Number of pages7
JournalBritish Journal of Cancer
Volume99
Issue number8
DOIs
Publication statusPublished - Oct 21 2008

Keywords

  • Breast cancer
  • IGFs
  • Polymorphism
  • Survival
  • TGF-β1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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