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Association of promoter polymorphisms of Fas –FasL genes with development of Chronic Myeloid Leukemia

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Tumor Biology

Abstract

Chronic myeloid leukemia (CML) is a monoclonal myeloproliferative disorder of hematopoietic stem cells (HSCs), characterized by reciprocal translocation, leading to the formation of BCR-ABL oncogene with constitutive tyrosine kinase (TK) activity. This oncogene is known to deregulate different downstream pathways which ultimately lead to cell proliferation, defective DNA repair, and inhibition of apoptosis. Fas (Fas cell surface death receptor) is a member of tumor necrosis factor (TNF) superfamily which interacts with its ligand, FasL, to initiate apoptosis. Promoter polymorphisms in Fas-FasL genes are known to influence the apoptotic signaling. Hence, the present study has been aimed to find out the association of the promoter polymorphisms in Fas and FasL genes with the development and progression of CML. Blood samples from 772 subjects (386 controls and 386 cases) were collected and genotyped for Fas-FasL gene polymorphisms through PCR-RFLP method. The association between SNPs and clinical outcome was analyzed using statistical softwares like SPSS version 20, SNPSTATs, and Haploview 2.1. The study revealed a significant association of Fas −670 G>A and FasL −844 T>C polymorphisms with the development of CML while Fas −670 AG was associated with accelerated phase. Combined risk analysis by taking the risk genotypes in cases and controls revealed a significant increase in CML risk with increase in number of risk genotypes (one risk genotype—OR 1.99 (1.44–2.76), p < 0.0001; two risk genotypes—OR 3.33 (1.91–5.81), p < 0.0001). Kaplan–Meier survival analysis of Fas −670 A>G and FasL −844 T>C showed reduced event-free survival in patients carrying the variant genotypes, Fas −670 GG, 32.363 ± 6.33, and FasL −844 CC, 33.489 ± 5.83, respectively. Our findings revealed a significant association of Fas −670 GG, FasL −844 TC, and CC genotypes with increased risk of CML.

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Acknowledgments

We are grateful to the Council of Scientific Research-Extra Mural Research (CSIR-EMR-II) project (vide no-027/ (0258)/12/EMR-II) and Osmania University-Department of Science and Technology (OU-DST)-PURSE program, Osmania University, for the financial assistance to carry out the research work. We would like to express our deep gratitude to all the patients and volunteers who participated in the study.

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Authors and Affiliations

  1. Department of Genetics, Osmania University, Hyderabad, 500007, India

    Prajitha Mohandas Edathara, Manjula Gorre, Sugunakar Vuree, Anuradha Cingeetham, Santhoshi Rani Nanchari, Phanni bhushann Meka, Sandhya Annamaneni & Vishnupriya Satti

  2. Homi Bhabha Cancer Hospital and Research Centre, Visakhapatnam, 530053, India

    Sailaja Kagita & Raghunadha Rao Digumarthi

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  1. Prajitha Mohandas Edathara
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  2. Manjula Gorre
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Edathara, P.M., Gorre, M., Kagita, S. et al. Association of promoter polymorphisms of Fas –FasL genes with development of Chronic Myeloid Leukemia. Tumor Biol. 37, 5475–5484 (2016). https://doi.org/10.1007/s13277-015-4295-0

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