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Aberrant promoter hypermethylation of p21 (WAF1/CIP1) gene and its impact on expression and role of polymorphism in the risk of breast cancer

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Abstract

p21 (Waf-1) is a cyclin-dependent kinase inhibitor that plays essential roles in cell growth arrest, terminal differentiation, and apoptosis. Statistically significant difference in the level of methylation of p21/CIP1 (p < 0. 05) between the patients with breast cancer and the healthy controls was observed. Risk of breast cancer was increased in patients with hypermethylated p21/CIP1 promoter by 2.31-fold (OR = 2.31, 95 % CI 1.95–2.74). The downregulation of p21/CIP1 mRNA expression was statistically significant in patients with methylated promoter (p < 0.00) in comparison to patients with unmethylated genes. Downregulation of mRNA expression of p21/CIP1 was up to 79 % due to promoter hypermethylation. We examined several p21/CIP1 genotypes in the patients with breast cancer and found that there is no significant association of these p21/CIP1 genotypes with the risk of developing breast cancer. However, a significant 2.21-fold increase in the chance of developing breast cancer was observed in the candidates carrying at least one allele Arg mutant in p21/CIP1 genotype (i.e., Ser/Arg + Arg/Arg) with age >50 (OR = 2.21; 95 % CI 1.03–4.79).

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Acknowledgments

We are indebted to the staff of PGIMER for providing the clinical samples.

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Authors and Affiliations

  1. Department of Biotechnology, Panjab University, Chandigarh, India

    Marjan Askari & Ranbir Chander Sobti

  2. Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Mohsen Nikbakht

  3. Department of Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Suresh C. Sharma

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  1. Marjan Askari
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Correspondence to Ranbir Chander Sobti.

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Askari, M., Sobti, R.C., Nikbakht, M. et al. Aberrant promoter hypermethylation of p21 (WAF1/CIP1) gene and its impact on expression and role of polymorphism in the risk of breast cancer. Mol Cell Biochem 382, 19–26 (2013). https://doi.org/10.1007/s11010-013-1696-5

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