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ADRA2A Germline Gene Polymorphism is Associated to the Severity, but not to the Risk, of Breast Cancer

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Pathology & Oncology Research

Abstract

Breast cancer (BC) prognosis and risk were associated to obesity, metabolic syndrome and type 2 diabetes mellitus. Two Single Nucleotide Polymorphisms (SNPs) of the adrenergic receptor-2a gene (ADRA2A): rs1800544 and rs553668, have been associated to these metabolic disorders. We investigated these SNPs in BC risk and prognosis. A total of 102 BC patients and 102 healthy controls were included. The rs1800544 and rs553668 were determined by real-time PCR. Genotypes and haplotypes frequencies between patients and controls, and for different clinico-pathologic parameters were compared. We found a significant association of rs1800544 GG genotype with young age at diagnosis, premenopausal status, higher tumor size, metastasis in lymph nodes, advanced TNM stages and higher Nottingham Prognosis Indicator (NPI) (p < 0.05). There was no association between rs1800544 and SBR stages, Her2, ER and PR statuses and the molecular classification. The rs553668 AA genotype was associated to young age at diagnosis and premenopausal status (p < 0.05). The haplotype GA was associated to the early age of diagnosis (p = 0.03), and the haplotype GG to higher tumor size, lymph node involvement, advanced TNM stages and Her2 positive status (p < 0.05). There was no polymorphism or haplotype association with BC risk (p > 0.05). ADRA2A polymorphism is associated with indicators BC poor prognosis but not with BC susceptibility. This is the first report suggesting that ADRA2A germline gene polymorphism could represent a predictor factor for BC outcome. Further investigation of other ADRA2A polymorphisms in BC risk or prognosis are needed and may lead to a genotype-based therapy.

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Acknowledgments

The authors thank the patients and control subjects for their participation.

Authors' Contributions

GB conceived of the study, obtained financial support for the project, carried out genotyping, carried out the statistical analyses, managed the project, coordinated data collection and wrote the manuscript. BK carried out genotyping, retrieved the clinical data and wrote the manuscript. WB and KH retrieved the clinical data. WT and MS carried out genotyping. HB co-ordinated data collection.

All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Faculty of Sciences, Batna 1 University, Batna, Algeria

    Batoul Kaabi

  2. Faculty of Medicine, Batna 2 University, 05000, Citée Ezzouhour, Batna, Algeria

    Ghania Belaaloui, Wassila Benbrahim, Kamel Hamizi & Hocine Bounecer

  3. Anti-Cancer Center, Batna, Algeria

    Wassila Benbrahim & Kamel Hamizi

  4. LAM Laboratory, Batna, Algeria

    Mourad Sadelaoud & Wided Toumi

  5. Epidemiology Unit, University Hospital Center, Batna, Algeria

    Hocine Bounecer

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  1. Batoul Kaabi
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  2. Ghania Belaaloui
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  4. Kamel Hamizi
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Correspondence to Ghania Belaaloui.

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Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in this study are in accordance with the ethical standards of the Thematic Agency for Research in Health Sciences (ATRSS, ex-ANDRS) 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.

Funding

This work was funded by contract No. 71/ANDRS/2011, from the Ministry of Higher Education and Scientific Research in Algeria.

Additional information

Batoul Kaabi and Ghania Belaaloui contributed equally to this work.

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Kaabi, B., Belaaloui, G., Benbrahim, W. et al. ADRA2A Germline Gene Polymorphism is Associated to the Severity, but not to the Risk, of Breast Cancer. Pathol. Oncol. Res. 22, 357–365 (2016). https://doi.org/10.1007/s12253-015-0010-0

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