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Journal of Cancer Research and Clinical Oncology

Erschienen in:

23.01.2018 | Original Article – Cancer Research

Transforming growth factor beta 1 (TGFβ1) polymorphisms and haplotype structures have dual roles in breast cancer pathogenesis

verfasst von: Glauco Akelinghton Freire Vitiello, Roberta Losi Guembarovski, Bruna Karina Banin Hirata, Marla Karine Amarante, Carlos Eduardo Coral de Oliveira, Karen Brajão de Oliveira, Guilherme Cesar Martelossi Cebinelli, Alda Losi Guembarovski, Clodoaldo Zago Campos, Maria Angelica Ehara Watanabe

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 4/2018

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Abstract

Purpose

Despite the documented dual role of TGFβ1 in breast cancer (BC) pathogenesis, the subtype-specific influences of its polymorphisms remain undocumented. The present study investigated the effects of the TGFB1 promoter region (rs1800468 or G-800A and rs1800469 or C-509T) and signal peptide (rs1800470 or C29T and rs1800471 or G74C) single nucleotide polymorphisms (SNPs) and their haplotype structures on the susceptibility and clinicopathological presentation of BC subtypes.

Methods

TGFB1 genotypes were assessed by PCR-RFLP and haplotype structures were inferred for 323 BC patients and 405 neoplasia-free women, and case–control analyses were performed by logistic regression adjusted by age. Clinicopathological parameters (age at diagnosis, tumor size, histopathological grade, lymph node metastasis, proliferation index and disease stage) were tested for correlation with TGFB1 variants. All statistical analyses were two-tailed with an alpha level of 0.05.

Results

Variants related to increased TGFβ1 production (C-509T SNP and GTCG haplotype) were associated with increased susceptibility to HER2⁺ tumors and correlated with worse prognostic parameters in HER2⁺ and triple-negative (TN) BCs, but correlated negatively to Ki67 in ER/PR⁺HER2⁻ tumors. Conversely, low TGFβ1 production variants (C29T SNP and GCTG haplotype) were protective against HER2⁺ tumors and correlated negatively with prognostic parameters in HER2⁺ and TN BCs, while indicating higher proliferation rates in ER/PR⁺HER2⁻ tumors. Furthermore, the GCCG haplotype was associated with decreased susceptibility to ER/PR⁺HER2⁻ tumors, but correlated positively with Ki67 in this subgroup.

Conclusion

The present study indicates that TGFB1 variants have subtype-specific roles in BC and may switch from tumor suppressor to promoter during tumor development, consistent with TGFβ1 dual role in BC pathogenesis.

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Titel: Transforming growth factor beta 1 (TGFβ1) polymorphisms and haplotype structures have dual roles in breast cancer pathogenesis
verfasst von: Glauco Akelinghton Freire Vitiello
Roberta Losi Guembarovski
Bruna Karina Banin Hirata
Marla Karine Amarante
Carlos Eduardo Coral de Oliveira
Karen Brajão de Oliveira
Guilherme Cesar Martelossi Cebinelli
Alda Losi Guembarovski
Clodoaldo Zago Campos
Maria Angelica Ehara Watanabe
Publikationsdatum: 23.01.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 4/2018
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-018-2585-9

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Transforming growth factor beta 1 (TGFβ1) polymorphisms and haplotype structures have dual roles in breast cancer pathogenesis

Abstract

Purpose

Methods

Results

Conclusion

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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