MDM2 SNP309 associates with accelerated pancreatic adenocarcinoma formation.
OBJECTIVE
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.
Grochola
Lukasz F
LF
Department of General, Visceral and Transplantation Surgery, University of Ulm, Ulm, Germany. lukasz.grochola@ludwig.ox.ac.uk
Müller
Thomas H
TH
Bond
Gareth L
GL
Taubert
Helge
H
Udelnow
Andrej
A
Würl
Peter
P
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012737:Sex Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2