Genetic polymorphisms in the TGF-beta 1 gene and breast cancer survival: a report from the Shanghai Breast Cancer Study.

The effect of genetic polymorphisms in the TGF-beta1 gene at codon 10 (T+29C), codon 25 (G+74C), and the promoter region [C --> T at -509 from the transcription site, (C-509T)] on breast cancer survival was evaluated among a cohort of 1111 patients. The median follow-up time for the cohort was 5.17 years after cancer diagnosis. No DNA sequence variation at codon 25 of the TGF-beta1 gene was found, whereas polymorphisms in C-509T and T+29C were in strong linkage disequilibrium. Patients who carried the C allele of T+29C polymorphism had a reduced 5-year disease-free survival rate (75.6% for T/C, and 78.2% for C/C) compared with the T/T genotype (85.1%; P, 0.04); the age-adjusted hazard ratio was 1.5 (95% confidence interval, 1.1-2.2). Adjustment for clinical prognostic factors slightly attenuated the association (hazard ratio, 1.4, 95% confidence interval, 1.0-1.9). Our study suggests that genetic polymorphisms in the TGF-beta1 gene may play a role in breast cancer progression.

[1]  L. Wakefield,et al.  TGF-β switches from tumor suppressor to prometastatic factor in a model of breast cancer progression , 2003 .

[2]  J. Chang-Claude,et al.  A Transforming Growth Factorβ1 Signal Peptide Variant Increases Secretion in Vitro and Is Associated with Increased Incidence of Invasive Breast Cancer , 2003 .

[3]  N. Todorović-Raković,et al.  Elevated plasma levels of transforming growth factor-beta 1 (TGF-beta 1) in patients with advanced breast cancer: association with disease progression. , 2003, European journal of cancer.

[4]  C. Arteaga,et al.  Blockade of TGF-β inhibits mammary tumor cell viability, migration, and metastases , 2002 .

[5]  R. Akhurst.  TGF-β antagonists: Why suppress a tumor suppressor? , 2002 .

[6]  B. Ponder,et al.  Effect of germ-line genetic variation on breast cancer survival in a population-based study. , 2002, Cancer research.

[7]  Y. Ba,et al.  Enhancement of tumorigenic, metastatic and in vitro invasive capacity of rat mammary tumor cells by transforming growth factor-beta. , 2002, Cancer letters.

[8]  K. Armstrong.  Genetic susceptibility to breast cancer: from the roll of the dice to the hand women were dealt. , 2001, JAMA.

[9]  E. Ziv,et al.  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. , 2001, JAMA.

[10]  Marek,et al.  Plasma transforming growth factor β1 in breast cancer patients treated with CMF chemotherapy , 2000, Journal of clinical pharmacy and therapeutics.

[11]  T. Sellers,et al.  Association of menstrual and reproductive factors with breast cancer risk: Results from the Shanghai breast cancer study , 2000, International journal of cancer.

[12]  M. Yokota,et al.  Association of a T29-->C polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to myocardial infarction in Japanese. , 2000, Circulation.

[13]  MitsuhiroYokota,et al.  Association of a T29→C Polymorphism of the Transforming Growth Factor-β1 Gene With Genetic Susceptibility to Myocardial Infarction in Japanese , 2000 .

[14]  H. Lodish,et al.  Role of transforming growth factor beta in human disease. , 2000, The New England journal of medicine.

[15]  D. Grainger,et al.  TGF-β in blood: a complex problem , 2000 .

[16]  M. Barcellos-Hoff,et al.  Transforming growth factor-β and breast cancer: Mammary gland development , 2000, Breast Cancer Research.

[17]  Carlos L Arteaga,et al.  Transforming growth factor-β and breast cancer: Tumor promoting effects of transforming growth factor-β , 2000, Breast Cancer Research.

[18]  S. Parodi,et al.  Correlation between plasma transforming growth factor-beta 1 and second primary breast cancer in a chemoprevention trial. , 1998, European journal of cancer.

[19]  P. Sminia,et al.  Plasma transforming growth factor beta levels in breast cancer patients. , 1998, Oncology reports.

[20]  M. Anscher,et al.  Elevated Plasma Transforming Growth Factor-β1 Levels in Breast Cancer Patients Decrease After Surgical Removal of the Tumor , 1995, Annals of surgery.

[21]  B. Teicher.  Malignant Cells, Directors of the Malignant Process: Role of Transforming Growth Factor-beta , 2004, Cancer and Metastasis Reviews.

[22]  R. Cardiff,et al.  Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[23]  H. Lodish,et al.  Role of Transforming Growth Factor in Human Disease , 2000 .

[24]  T. Spector,et al.  Genetic control of the circulating concentration of transforming growth factor type beta1. , 1999, Human molecular genetics.

[25]  M. Sporn,et al.  Transforming Growth Factor-β1 Circulates in Normal Human Plasma and is Unchanged in Advanced Metastatic Breast Cancer , 1995 .