Molecular and Cellular Biochemistry

, Volume 382, Issue 1–2, pp 19–26 | Cite as

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

  • Marjan Askari
  • Ranbir Chander Sobti
  • Mohsen Nikbakht
  • Suresh C. Sharma


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).


p21 (Waf-1) Breast cancer Hypermethylation Expression Polymorphism 



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


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Marjan Askari
    • 1
  • Ranbir Chander Sobti
    • 1
  • Mohsen Nikbakht
    • 2
  • Suresh C. Sharma
    • 3
  1. 1.Department of BiotechnologyPanjab UniversityChandigarhIndia
  2. 2.Hematology-Oncology and Stem Cell Transplantation Research CenterTehran University of Medical SciencesTehranIran
  3. 3.Department of Radiotherapy and OncologyPost Graduate Institute of Medical Education and ResearchChandigarhIndia

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