Tumor Biology

, Volume 37, Issue 5, pp 6905–6912 | Cite as

Influence of BCL2-938 C>A promoter polymorphism and BCL2 gene expression on the progression of breast cancer

  • Phanni bhushann Meka
  • Sarika Jarjapu
  • Sandeep Kumar Vishwakarma
  • Santhoshi Rani Nanchari
  • Anuradha Cingeetham
  • Sandhya Annamaneni
  • Srinivasulu Mukta
  • B. Triveni
  • Vishnupriya Satti
Original Article

Abstract

BCL2 (B-cell leukemia/lymphoma 2) gene functions as antiapoptotic regulatory element and known to be associated with tumorigenesis. The SNP-938 (C>A) (rs2279115), located in the inhibitory P2 promoter of the BCL2 gene, influences differential binding affinities of transcriptional factors thereby affecting BCL2 expression. The present study is an attempt to evaluate the association between BCL2(-938C>A) polymorphism and clinical characteristics of breast cancer patients as well as to analyze BCL2 expression and Ki67 proliferation index with respect to the genotypes. One hundred ten primary breast cancer tumor tissues were genotyped for -938 C>A polymorphism through PCR-RFLP method as well as evaluated for BCL2 expression and ki67 proliferation index by immunohistochemistry. Evaluation of apoptosis level was performed by flowcytometry. The results revealed that AA genotype was associated with an increased risk (AA Vs AC + CC) by 2.86-fold (p = 0.07) for breast cancer development which reflected in elevated A allele frequency also. AA genotype was found to be predominant among BCL2 positive tumors as compared to BCL2 negative tumors. Further, AA genotype was found to be associated with advanced stage tumors, node positive status, and high Ki67 proliferation index compared to CA and CC genotypes indicating that elevated expression of BCL2 gene in the presence of A allele might be associated with decreased apoptosis and enhanced proliferation rate. AA genotype of BCL2-938C>A polymorphism might influence BCL2 gene expression there by associated with elevated risk for breast cancer progression. Probably, failure of apoptosis due to enhanced expression and antiapoptotic protein BCL2 might promote malignant growth.

Keywords

BCL2 Apoptosis Immunohistochemistry Ki67 proliferation index Flow cytometry Breast cancer 

Notes

Acknowledgments

We would like to thank MNJ institute of oncology and regional cancer centre, Hyderabad, India for providing samples from breast cancer patients.

Compliance with ethical standards

Conflicts of interest

None

Funding

This study was funded by University Grants Commission-Centre for Advanced Studies (UGC-CAS-II), New Delhi and DBT-OU-ISLARE. Phanni bhushann Meka is thankful to UGC-CAS-II for providing fellowship.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Phanni bhushann Meka
    • 1
  • Sarika Jarjapu
    • 1
  • Sandeep Kumar Vishwakarma
    • 2
  • Santhoshi Rani Nanchari
    • 1
  • Anuradha Cingeetham
    • 1
  • Sandhya Annamaneni
    • 1
  • Srinivasulu Mukta
    • 3
  • B. Triveni
    • 3
  • Vishnupriya Satti
    • 1
  1. 1.Department of GeneticsOsmania UniversityHyderabadIndia
  2. 2.Central Laboratory for Stem Cell Research & Translational Medicine, CLRDDeccan College of Medical SciencesHyderabadIndia
  3. 3.MNJ Institute of Oncology & Regional Cancer CentreHyderabadIndia

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