title: Influence of BCL2-938 C>A promoter polymorphism and BCL2 gene expression on the progression of breast cancer.
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.
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, 500007, India.
authors.forename: Phanni
authors.initials: P
authors.lastname: Bhushann Meka
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, 500007, India.
authors.forename: Sarika
authors.initials: S
authors.lastname: Jarjapu
authors.affiliation: Central Laboratory for Stem Cell Research & Translational Medicine, CLRD, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, India.
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Vishwakarma
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, 500007, India.
authors.forename: Santhoshi Rani
authors.initials: SR
authors.lastname: Nanchari
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, 500007, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Cingeetham
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, 500007, India.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Annamaneni
authors.affiliation: MNJ Institute of Oncology & Regional Cancer Centre, Hyderabad, India.
authors.forename: Srinivasulu
authors.initials: S
authors.lastname: Mukta
authors.affiliation: MNJ Institute of Oncology & Regional Cancer Centre, Hyderabad, India.
authors.forename: B
authors.initials: B
authors.lastname: Triveni
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, 500007, India. sattivishnupriya@gmail.com.
authors.forename: Vishnupriya
authors.initials: V
authors.lastname: Satti
mesh_terms: D000328:Adult; D000483:Alleles; D017209:Apoptosis; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: Apoptosis; BCL2; Breast cancer; Flow cytometry; Immunohistochemistry; Ki67 proliferation index