Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Young Researchers Club, Ahar Branch, Islamic Azad University, Ahar, Iran.
J Oncol. 2013;2013:738915. doi: 10.1155/2013/738915. Epub 2013 Dec 30.
The TP53 gene encodes tumor protein p53 which play a major role in the etiology of pancreatic cancer. The important role of codon 249 of TP53 for binding of p53 to its sequence-specific consensus site in DNA has been revealed by crystallography's studies, and mutation at this codon was detected in the plasma of some human cancers. The TP53 Mut assessor software within the International Agency for Research on Cancer (IARC) TP53 Database was performed to evaluate every possible mutation at codon 249. DNA was extracted from the plasma of 133 pancreatic cancer patients and 85 noncancer-bearing individuals. Exon 7 in TP53 was amplified, and mutation at R249 was identified by the endonuclease cleavage of HaeIII. The group of patients showed a frequency of 11% (22 of 133 samples) R249 mutation compared to 3.5% (3 of 85 samples) in the group of control which was significant (P = 0.03). This mutation demonstrated statistically significant association with pancreatic cancer risk in unadjusted odds ratio (OR: 3.74, 95% CI: 1.1-13.2; P = 0.041); however when adjusted for confounding factors, it was marginally significant because of lower control samples. These findings demonstrate that mutation at R249 of TP53 can be considered for increasing risk of pancreatic cancer that needs more research.
TP53 基因编码肿瘤蛋白 p53,在胰腺癌的病因学中起着重要作用。晶体学研究揭示了 TP53 密码子 249 对 p53 与其 DNA 序列特异性共有结合位点结合的重要作用,并且在一些人类癌症的血浆中检测到该密码子的突变。国际癌症研究机构 (IARC) TP53 数据库中的 TP53 Mut assessor 软件用于评估密码子 249 上的每一种可能突变。从 133 例胰腺癌患者和 85 例非癌症患者的血浆中提取 DNA。扩增 TP53 的外显子 7,并通过 HaeIII 内切酶切割鉴定 R249 突变。与对照组 3.5%(85 例样本中的 3 例)相比,患者组的 R249 突变频率为 11%(133 例样本中的 22 例),差异有统计学意义(P=0.03)。在未调整的比值比(OR:3.74,95%CI:1.1-13.2;P=0.041)中,该突变与胰腺癌风险呈统计学显著关联;然而,当调整混杂因素时,由于对照组样本较少,该关联仅具有边缘统计学意义。这些发现表明,TP53 密码子 249 的突变可被视为增加胰腺癌风险的因素,需要进一步研究。