Aberrant promoter hypermethylation of p21 (WAF1/CIP1) gene and its impact on expression and role of polymorphism in the risk of breast cancer
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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DOI：
10.1007/s11010-013-1696-5
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发表时间：
2013-10-01
影响因子：
4.3
通讯作者：
Sharma, Suresh C.
中科院分区：
文献类型：
--
作者：
Askari, Marjan;Sobti, Ranbir Chander;Sharma, Suresh C.
p21（Waf-1）是细胞周期蛋白依赖性激酶抑制剂，在细胞生长停滞、终末分化和凋亡中起重要作用。p21/CIP 1基因甲基化水平与正常对照组相比差异有统计学意义（p < 0. 05）。05)观察乳腺癌患者与健康对照组之间的差异。p21/CIP 1启动子高甲基化患者乳腺癌风险增加2.31倍（OR = 2.31，95%CI 1.95-2.74）。启动子甲基化患者p21/CIP 1 mRNA表达下调与非甲基化患者相比有统计学意义（p < 0.00）。p21/CIP 1基因启动子甲基化导致mRNA表达下调达79%。我们检测了乳腺癌患者的几种p21/CIP 1基因型，发现这些p21/CIP 1基因型与乳腺癌的发生风险无显著相关性。然而，在p21/CIP 1基因型中携带至少一个等位基因Arg突变体的候选者中观察到发生乳腺癌的机会显著增加2.21倍（即，Ser/Arg + Arg/Arg）（OR = 2.21; 95%CI 1.03-4.79）。
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).