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 ( ). This mutation demonstrated statistically significant association with pancreatic cancer risk in unadjusted odds ratio (OR: 3.74, 95% CI: 1.1–13.2; ); 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. 1. Introduction Pancreatic ductal adenocarcinoma (PDAC), the most common cancer of the pancreas, is the fifth commonest cause of cancer-related mortality among industrialized countries [1]. There is not much data regarding incidence and mortality of pancreatic cancer in Middle East. However the cancer of pancreas is not in the top 10 of cancer-related deaths in Iran [2]. The aggressive nature of the PDAC is related to poor prognosis; therefore, most of the patients at the time of diagnosis are harboring unsuitable cancer that is extremely resistant to chemotherapy [3]. The incidence rate of pancreatic cancer has been stabilizing over the past two decades in many developed countries; however, this continues to increase in countries where the rate of pancreatic cancer was relatively low four decades ago, such as Japan [4]. In Iran, pancreatic cancer is diagnosed in advanced stage with no identified risk factors. Pancreatic cancer is primarily an environmental disease and attributed mostly to cigarette smoking [5]; however the pathogenesis of this cancer also involves various genetic alterations particularly genes that controlled the cell cycle [6, 7]. The TP53 (tumor protein p53) as a main tumor suppressor gene is mutated in most of the tumors [8, 9]. The p53 protein inhibits cancer formation
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