Abstract
Single-nucleotide polymorphisms (SNPs) of TP53 (codon 72, rs1042522) and MDM2 promoter (SNP 309, rs2279744) have been associated with risk for various human cancers. However, studies analyzing these polymorphisms in pancreatic ductal adenocarcinoma (PDAC) are lacking. We investigated TP53 codon 72 and MDM2 SNP 309 polymorphisms in 32 patients with PDAC, 16 patients with chronic pancreatitis (CP), and 32 normal controls, using formalin-fixed paraffin-embedded tissue. We also examined TP53 and MDM2 protein immunohistochemistry (IHC) to assess the involvement of these differences in malignant transformation and disease progression. TP53 Pro/Pro genotype was significantly more frequent in PDAC patients than in controls (65.6 vs. 15.6%, p < 0.001) and no significant difference was found between CP patients (37.5%) and controls. In MDM2 SNP 309, there were no significant differences among the three groups. Based on the Kaplan-Meier analysis, overall survival was significantly shorter in MDM2 G/G genotypes compared with other genotypes (G/T and T/T) (359 vs. 911 days, p = 0.016) whereas no significant differences in TP53 genotypes were observed (638 vs. 752 days, p = 0.471). Although TP53 IHC was frequent in PDAC patients (53.1%), TP53 and MDM2 protein expression was not correlated with polymorphisms. Our study demonstrated TP53 codon 72 polymorphism is potentially a genetic predisposing factor while MDM2 SNP 309 polymorphism might be useful in predicting survival outcome.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is a gastrointestinal neoplasm with high malignancy and poor prognosis
Recent research has shown that single nucleotide polymorphisms (SNPs) of genes involved in the cell cycle play an important role in carcinogenesis [4,5,6,7] and that common polymorphisms may lead to altered susceptibility to PDAC and affect clinical outcome [7]
In the present study, using IHC we examined the tumor protein p53 (TP53) codon 72 and mouse double minute 2 (MDM2) SNP 309 polymorphisms and TP53 and MDM2 proteins in PDAC and chronic pancreatitis (CP) patients to assess the involvement of these differences in the malignant transformation and disease progression
Summary
Pancreatic ductal adenocarcinoma (PDAC) is a gastrointestinal neoplasm with high malignancy and poor prognosis. Incidence of PDAC has increased in recent years, but the therapeutic efficacy remains unsatisfactory. Complete surgical resection is an essential part of curative. TP53 Codon 72 and MDM2 SNP309 in Pancreatic Ductal Adenocarcinoma therapy. Most tumors are unresectable and are treated primarily with chemotherapy and/or radiation [1,2,3]. Recent research has shown that single nucleotide polymorphisms (SNPs) of genes involved in the cell cycle play an important role in carcinogenesis [4,5,6,7] and that common polymorphisms may lead to altered susceptibility to PDAC and affect clinical outcome [7]
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