MDM2 SNP 309 and p53 codon 72 polymorphisms are associated with the outcome of oral carcinoma patients receiving postoperative irradiation.
OBJECTIVE
The p53 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 p53. 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 p53 codon 72 results in an Arg/Pro polymorphism, which is associated with apoptosis induction potential and p53 mutation status.


METHODS
We sequenced both MDM2 SNP309 and p53 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 p53 codon 72 SNP was associated with susceptibility to or the age at onset of OSCC or OSF. p53 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 p53 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 p53 codon 72 SNP could be useful factors for evaluating the outcome of advanced OSCC treated with adjuvant radiation.
Tu
Hsi-Feng
HF
Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.
Chen
Hong-Wen
HW
Kao
Shou-Yen
SY
Lin
Shu-Chun
SC
Liu
Chung-Ji
CJ
Chang
Kuo-Wei
KW
D000328:Adult; D000704:Analysis of Variance; D001114:Areca / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D016022:Case-Control Studies; D003062:Codon; D005355:Fibrosis / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D003062:Codon; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2