Impact of TP53 Codon 72 and MDM2 SNP 309 Polymorphisms in Pancreatic Ductal Adenocarcinoma

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.

The Role of p16 and MDM2 Gene Polymorphisms in Prolactinoma: MDM2 Gene Polymorphisms May Be Associated with Tumor Shrinkage

“…However, they found patients with MDM2 GG genotype had shorter total life expectancy compared to those with other (TG, TT) genotypes (40). Another study by Chua et al reported MDM2 TT genotype was associated with lung cancer in non-smoking women in a Chinese population (41). A similar study in the same population showed the G allele was associated with increased risk of cancer; however, early age of onset was found to be associated with the TT genotype (42).…”

p53 R72P Alone and in Combination with MDM2 SNP T309G is Associated with Colon Carcinoma Incidence and Survival

“…The best explanation of this came from the knowledge of different polymorphic variants of various genes; particularly those involved in cell cycle control and DNA repair mechanism, and their frequency varies among different population. p53 is one of the most studied proteins that plays fundamental role in regulating basic cellular function and because of this, it is an important target protein to study different polymorphic variants of p53 for their association with various diseases including colon carcinomas [10,[12][13][14]27]. A SNP in MDM2 (SNPT309G), a negative regulator of p53, alone or in combination with p53 has been reported to associate with different carcinomas and progression of disease [14,18,22,23,25,[27][28][29][30].…”

“…p53 is one of the most studied proteins that plays fundamental role in regulating basic cellular function and because of this, it is an important target protein to study different polymorphic variants of p53 for their association with various diseases including colon carcinomas [10,[12][13][14]27]. A SNP in MDM2 (SNPT309G), a negative regulator of p53, alone or in combination with p53 has been reported to associate with different carcinomas and progression of disease [14,18,22,23,25,[27][28][29][30]. Over the last decade, studies have reported the role of p53 R72P and MDM2 T309G polymorphisms as risk factor for colorectal carcinoma [14,15,19,[23][24][25].…”

<p>Is there a CDKN2A-centric network in pancreatic ductal adenocarcinoma?</p>

“…Hence, affecting the AURORA signaling pathway by influencing TP53 and MDM2 can indirectly lead to changes in the occurrence and progression of PDAC. 85 In the past, many signaling pathways, nutrients and natural products interacted with pathways involved in TP53 and drug resistance. 86 TP53-positive chronic pancreatitis is considered inefficient in inducing carcinogenesis.…”