MDM2 SNP 309 and p 53 codon 72 polymorphisms are associated with the outcome of oral carcinoma patients receiving postoperative irradiation

Background and Purpose: The p 53 tumor suppression pathway is important in effects associated with radiotherapy. The mouse double minute 2 (MDM2) plays a pivotal role in this pathway by down regulating p 53. A functional T-to-G polymorphism at nucleotide 309 in MDM2 promoter intron 1 (SNP309) has been identified which influenced transcription activity. A G-to-C SNP at p 53 codon 72 results in an Arg/Pro polymorphism, which is associated with apoptosis induction potential and p 53 mutation status. Materials and methods: We sequenced both MDM2 SNP309 and p 53 codon 72 SNP in patients with oral squamous cell carcinoma (OSCC, n = 189), oral submucosal fibrosis (OSF, n = 70), and 116 controls. Results: Neither MDM2 SNP309 nor p 53 codon 72 SNP was associated with susceptibility to or the age at onset of OSCC or OSF. p 53 codon 72 SNP Arg/Arg polymorphism was associated with the progression of OSCC, and the overall (OS) and disease-free survival (DFS) of irradiated patients. The MDM2 SNP309 G/G polymorphism was associated with poor OS in advanced OSCC, and the OS and DSF of irradiated patients. The combination of MDM2 SNP309 G/G and p 53 codon 72 Arg/Arg polymorphism is associated with the worst OS and DFS. Conclusions: Advanced OSCC has high mortality and recurrence. We identified that both MDM2 SNP309 and p 53 codon 72 SNP could be useful factors for evaluating the outcome of advanced OSCC treated with adjuvant radiation.