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

Abstract

Transforming growth factor-b (TGF-b)-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-b1 at T29C and TGF-b1 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-b1 genotype and phenotype were analysed with TaqMan s 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-b1 and disease outcomes. Patients with the T/T (29%) genotype at T29C had the highest TGF-b1, 707.9 pg mg À1 , followed by the T/C (49%), 657.8 pg mg À1 , and C/C (22%) genotypes, 640.8 pg mg À1 , (P ¼ 0.210, T/T vs C/C and C/T). TGF-b1 concentrations were positively correlated with levels of oestrogen receptor, IGF-I, IGF-II and IGFBP-3. Survival analysis showed TGF-b1 associated with disease progression, but the association differed by disease stage. For early-stage disease, patients with the T/T genotype or high TGF-b1 had shorter overall survival compared to those without T/T or with low TGF-b1; 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 ¼ 0.13, 95% CI: 0.02 -1.00), whereas no association was found between TGF-b1 phenotype and survival outcomes. The study suggests a complex role of TGF-b1 in breast cancer progression, which supports the finding of in vitro studies that TGF-b1 has conflicting effects on tumour growth and metastasis.

Expression of TGF-β signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics

“…Extracellular-TGF-β1 expression was associated with ER-positive status, consistent with previous reports [24, 25] despite differences in the TGF-β1 assays employed (including enzyme-linked immunosorbent assays). However, we did not confirm the prior finding that TGF-β1 expression is more frequent in tumors with lymph node metastases although the percentage of extracellular-TGF-β1-positive tumors was similar to the previous report [24].…”

Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study

“…Intra-tumoral expression of TGF-β1 has been found to be significantly higher in invasive breast cancer patients [55]. It is well documented that TGF-β1 polymorphic variants are functionally associated with the level of TGF-β1 expression [40], [56]–[57]. Therefore, it is plausible that TGF-β1 polymorphisms affect breast cancer risk by modulating the level of TGF-β1 expression.…”

The influence of genetic ancestry and ethnicity on breast cancer survival associated with genetic variation in the TGF-β-signaling pathway: The Breast Cancer Health Disparities Study

“…Some studies have shown that TGF-β1 protein levels are associated with shorter disease-free survival, especially among those with node-negative tumors[9], whereas others have reported associations between TGFβ1-expressing tumors and a greater likelihood of breast cancer recurrence[43, 44]. A study by Mu [45] found significantly higher TGF-β1 expression with the TT genotype of rs1982073, with an accompanying two-fold increase in risk of breast cancer death; the study by Zheng supported these findings [46]. We found a similar association with rs1800469 for women with higher levels of NA ancestry, but not for women with low NA ancestry.…”