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Glutathione S-transferases deletions may act as prognosis and therapeutic markers in breast cancer

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Abstract

Breast cancer (BC) is the main worldwide neoplasia in women. The metabolic balance between xenobiotic absorption and elimination rates plays an important role in preventing DNA damage and, consequently, tumor development. The glutathione S-transferases (GSTs), such as GSTM1 and GSTT1, and the NAD(P)H quinone oxidoreductase are important enzymes involved in phase II detoxification reactions. Deletions in GSTM1 and GSTT1, and single-nucleotide polymorphism (SNP) in NQO1 (rs1800655) have been investigated in cancer context, revealing conflicting results. The present study analyzed these genetic polymorphisms in 121 BC patients and 151 BC-free controls in order to verify if they could act as susceptibility modifiers and/or prognostic factors. Binary logistic regressions adjusted by age were performed to assess associations between allelic variants and interactions in polymorphisms combination with BC susceptibility, but no significant association was found. Genotypes distribution was also compared between BC subtypes, but no significant difference was observed (p > 0.05). GSTM1 deletion was significantly associated with histopathological grade, with a greater proportion of patients presenting grade III tumors (p = 0.007). Univariate analysis identified tumor size as the only clinicopathological parameter potentially associated with recurrence risk in patients that received adjuvant chemotherapy (p < 0.1). Thus, logistic regression analysis adjusted by tumor size revealed a positive association between GSTT1 deletion and recurrence risk in general BC (OR 4.25; p = 0.04), while GSTM1 was negatively associated with recurrence risk in ER/PR+HER2− samples (OR 0.07; p = 0.03). In conclusion, the present study indicated that GSTT1 deletion was associated with increased recurrence risk, while GSTM1 correlated with worst prognosis parameters at diagnosis, but was negatively associated with recurrence risk in luminal subtype samples.

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Acknowledgements

We acknowledge the volunteers who made this study possible, the Londrina Cancer Hospital and Orlando Sestari Primary Health Care Unit staff for helping during sample collection and patient’s recruitment.

Funding

This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq, the Fundação Araucária and the Coordenadoria de Pós-Graduação, Londrina State University, Brazil.

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Authors and Affiliations

  1. Department of Medicine, Health Sciences Center, Londrina State University, Londrina, Parana, Brazil

    Clodoaldo Zago Campos

  2. Department of Clinical Research, Londrina Cancer Hospital, Londrina, Parana, Brazil

    Clodoaldo Zago Campos

  3. Department of General Biology, Biological Sciences Center, Londrina State University, Londrina, Parana, Brazil

    Roberta Losi Guembarovski

  4. Laboratory of Studies and Applications of DNA Polymorphisms, Department of Pathological Sciences, Biological Sciences Center, Londrina State University, Celso Garcia Cid Highway, PR 445, Km 380, Londrina, Parana, Brazil

    Carlos Eduardo Coral de Oliveira, Bruna Karina Banin Hirata, Glauco Akelinghton Freire Vitiello, Flávia Luísa Dias, Carlos Hiroji Hiroki & Maria Angelica Ehara Watanabe

  5. Endocrine Interactions Research Group, Department of Medical Clinic, Health Sciences Center, Londrina State University, Londrina, Parana, Brazil

    Tânia Longo Mazzuco

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  1. Clodoaldo Zago Campos
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  2. Roberta Losi Guembarovski
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  3. Carlos Eduardo Coral de Oliveira
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  8. Maria Angelica Ehara Watanabe
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  9. Tânia Longo Mazzuco
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Correspondence to Maria Angelica Ehara Watanabe.

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The authors declare that they have no conflict of interest regarding the publication of the manuscript.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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

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Campos, C.Z., Losi Guembarovski, R., de Oliveira, C.E.C. et al. Glutathione S-transferases deletions may act as prognosis and therapeutic markers in breast cancer. Clin Exp Med 18, 27–35 (2018). https://doi.org/10.1007/s10238-017-0461-6

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  • DOI: https://doi.org/10.1007/s10238-017-0461-6

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