Transforming growth factor beta 1 (TGFβ1) plasmatic levels in breast cancer and neoplasia-free women: Association with patients’ characteristics and TGFB1 haplotypes

Abstract

Transforming growth factor beta 1 (TGFβ1) is a pleiotropic cytokine that acts in a context-dependent manner. In breast cancer (BC) this cytokine exerts subtype- and stage-specific roles, inhibiting poorly aggressive tumors while enhances the invasive potential of highly aggressive cancers. Single-nucleotide polymorphisms (SNPs) affecting TGFβ1 production largely reflect this pattern of association, but studies investigating systemic TGFβ1 levels in BC patients and their association with clinical features or SNPs produced conflicting conclusions. Therefore, the present work investigated plasmatic TGFβ1 levels through enzyme linked immunosorbent assay (ELISA) in 341 individuals previously genotyped for four TGFB1 SNPs [G-800A (rs1800468), C-509T (rs1800469), T29C (rs1800470) and G74C (rs1800471)], encompassing 184 neoplasia-free women with clinical information regarding health status, 113 treatment-free pre-surgery BC patients and 44 treated BC patients. Results have shown that TGFβ1 levels varied greatly in function of health status in neoplasia-free women, and disease-free individuals had higher TGFβ1 levels than both treatment-free or treated BC patients. There was no correlation between TGFβ1 with clinicopathological features in treatment-free BC general group, but it was negatively correlated with tumor size in luminal-B-HER2+ patients and with histopathological grade in triple-negative group. Also, TGFB1 ACTG haplotype (from G-800A to G74C) was associated with decreased TGFβ1 levels compared to the reference GCTG haplotype, and regression analyses showed that this association was independent of age, health status or BC diagnosis. In conclusion, several factors may influence TGFβ1 levels, and ACTG haplotype seems to be an important factor regulating TGFβ1 production.