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 language | English |
|---|---|
| Pages (from-to) | 1357-1363 |
| Number of pages | 7 |
| Journal | British Journal of Cancer |
| Volume | 99 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Oct 21 2008 |
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Keywords
- Breast cancer
- IGFs
- Polymorphism
- Survival
- TGF-β1
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
TGF-β1 genotype and phenotype in breast cancer and their associations with IGFs and patient survival. / Mu, L.; Katsaros, D.; Lu, L.; Preti, M.; Durando, A.; Arisio, R.; Yu, H.
In: British Journal of Cancer, Vol. 99, No. 8, 21.10.2008, p. 1357-1363.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TGF-β1 genotype and phenotype in breast cancer and their associations with IGFs and patient survival
AU - Mu, L.
AU - Katsaros, D.
AU - Lu, L.
AU - Preti, M.
AU - Durando, A.
AU - Arisio, R.
AU - Yu, H.
PY - 2008/10/21
Y1 - 2008/10/21
N2 - 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.
AB - 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.
KW - Breast cancer
KW - IGFs
KW - Polymorphism
KW - Survival
KW - TGF-β1
UR - http://www.scopus.com/inward/record.url?scp=53849129518&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=53849129518&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6604689
DO - 10.1038/sj.bjc.6604689
M3 - Article
C2 - 18827819
AN - SCOPUS:53849129518
VL - 99
SP - 1357
EP - 1363
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 8
ER -