Breast Cancer Research and Treatment

, Volume 178, Issue 1, pp 207–219 | Cite as

Transforming growth factor beta receptor II (TGFBR2) promoter region polymorphism in Brazilian breast cancer patients: association with susceptibility, clinicopathological features, and interaction with TGFB1 haplotypes

  • Glauco Akelinghton Freire Vitiello
  • Marla Karine Amarante
  • Bruna Karina Banin-Hirata
  • Clodoaldo Zago Campos
  • Karen Brajão de Oliveira
  • Roberta Losi-Guembarovski
  • Maria Angelica Ehara WatanabeEmail author



Transforming growth factor beta (TGFβ) has paradoxical effects in breast cancer (BC), inhibiting initial tumors while promoting aggressive ones. A polymorphism on TGFBR2 promoter region (G-875A, rs3087465) increases TGFβ type II receptor expression and is protective against cancer. Previously, we have shown that TGFB1 variants have subtype-specific roles in BC. This work sought to investigate the association between TGFBR2 and susceptibility and clinicopathological features in BC subgroups.


TGFBR2 G-875A was analyzed through PCR-RFLP in 388 BC patients and 405 neoplasia-free women. Case–control analyses as well as interaction with TGFB1 haplotypes previously associated with BC were tested through age-adjusted logistic regression. Correlations between G-875A and clinicopathological parameters were assessed through Kendall’s Tau-b test. All statistical tests were two-tailed (α = 0.05).


TGFBR2 G-875A was protective against BC in additive, genotypic, and dominant models. In subgroup-stratified analyses, these effects were greater in hormonal receptor-positive and luminal-A tumors, but were not significant in other subgroups. Logistic models including TGFB1 variants showed that in luminal-A tumors, G-875A retained its significance while TGFB1 haplotype showed a trend towards significance; otherwise, in HER2+ tumors TGFB1 variants remained significant while TGFBR2 showed a trend for association. There was no interaction between these genes. In correlation analyses, G-875A positively correlated with histopathological grade in total sample, and a trend towards significance was observed in triple-negative BCs.


These results indicate that G-875A is a protective factor against BC, especially from luminal-A subtype, but may promote anaplasia in established tumors, consistent with TGFβ signaling roles in BC.


Transforming growth factor beta TGFBR2 Polymorphism Breast neoplasm Disease susceptibility 



The authors acknowledge all the volunteer donors involved in this study and the Clinical Hospital (HC-UEL) and Londrina Cancer Hospital (HCL) staff for supporting during sample collection.


This study was supported by the Brazilian National Council for Scientific and Technological Development (CNPq, process 303186/2015-1), Fundação Araucária (1027/2013), and by the Londrina State University Postgraduate Coordination (PROPPG-UEL).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ethics Committee for Research Involving Human Subjects from Londrina State University - CEP/UEL 189/2013—CAAE 17123113400005231) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10549_2019_5370_MOESM1_ESM.docx (199 kb)
Supplementary material 1 (DOCX 199 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Glauco Akelinghton Freire Vitiello
    • 1
  • Marla Karine Amarante
    • 1
  • Bruna Karina Banin-Hirata
    • 1
  • Clodoaldo Zago Campos
    • 2
    • 5
  • Karen Brajão de Oliveira
    • 1
  • Roberta Losi-Guembarovski
    • 3
  • Maria Angelica Ehara Watanabe
    • 1
    • 4
    Email author
  1. 1.Department of Pathological SciencesBiological Sciences Center, Londrina State UniversityLondrinaBrazil
  2. 2.Department of Clinical ResearchLondrina Cancer HospitalLondrinaBrazil
  3. 3.Department of General BiologyBiological Sciences Center, Londrina State UniversityLondrinaBrazil
  4. 4.Laboratory of DNA Polymorphisms and Immunology, Department of Pathological SciencesBiological Sciences Center, Londrina State UniversityLondrinaBrazil
  5. 5.Department of Clinical Medicine, Health Sciences CenterLondrina State UniversityLondrinaBrazil

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