Impact of MDM2 single nucleotide polymorphism on tumor onset in head and neck squamous cell carcinoma.
CONCLUSIONS
The GG genotype of MDM2 SNP309 is associated with an earlier onset of head and neck squamous cell carcinoma (HNSCC) in the Japanese population. SNP309 may be a key factor in the tumorigenesis of HNSCC as well as other hereditary or sporadic tumors.


OBJECTIVE
This study was designed to evaluate the association between the single nucleotide polymorphism (SNP) 309 in the MDM2 gene with HNSCC. An MDM2 protein down-regulates the p53 pathway. Recently, an important SNP was discovered in the MDM2 promoter region, which could affect the tumorigenesis of HNSCC by attenuation of the p53 pathway.


METHODS
Patients with 103 HNSCCs were genotyped using direct sequencing and real-time PCR. The relationship between the SNP309 genotypes and the clinicopathological features was statistically analyzed.


RESULTS
The number of patients genotyped to TT, TG, and GG was 29 (28%), 46 (44.7%), and 28 (27.2%), respectively. The average age at tumor onset was 65.6 years for TT, 62.9 years for TG, and 56.7 years for GG. The patients with the GG genotype had a significantly earlier tumor onset in comparison to those with the TT genotype (p=0.032).
Nakashima
Masashi
M
Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
Kondo
Satoru
S
Shimizu
Yoshinori
Y
Wakisaka
Naohiro
N
Murono
Shigeyuki
S
Furukawa
Mitsuru
M
Yoshizaki
Tomokazu
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012189:Retrospective Studies
D004247:DNA; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2