MDM2 SNP309 Associates With Accelerated Pancreatic Adenocarcinoma Formation

Objectives: The G-allele of a single nucleotide polymorphism in the promoter of the MDM2 gene (MDM2 SNP309, T/G) associates with the acceleration of tumor formation and an increased risk for developing various malignancies. In this report, the possible role of the MDM2 SNP309 locus with regard to sex, age, and p53 mutational status in the development and progression of pancreatic ductal adenocarcinoma (PDAC) was examined. Methods: One hundred three PDAC patients with comprehensive clinical, histopathologic, and follow-up data and 499 controls were included into the study and their MDM2 SNP309 genotypes obtained. Results: Interestingly, the G-allele of MDM2 SNP309 is shown to associate with a 9-year earlier age of PDAC onset (P = 0.021). However, in contrast to studies of other tumor types, these observations are made predominantly in men and not women. Conditions of male PDAC patients with a G/G genotype are diagnosed at a mean of 12 years earlier than T-allele carriers (P = 0.0032). Furthermore, particularly younger male patients present a significant enrichment of the G-allele (P = 0.019). Conclusions: These observations suggest a novel role of the MDM2 SNP309 locus in regulating PDAC tumor formation in a male-specific manner.