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

作者：Askari Marjan; Sobti Ranbir Chander^*; Nikbakht Mohsen; Sharma Suresh C

来源：Molecular and Cellular Biochemistry, 2013, 382(1-2): 19-26.

DOI：10.1007/s11010-013-1696-5

• p21 (Waf-1)
• Breast cancer
• Hypermethylation
• Expression
• Polymorphism

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 %26lt; 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 %26lt; 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 %26gt; 50 (OR = 2.21; 95 % CI 1.03-4.79).

• 出版日期2013-10
• 单位河北医科大学