title: Combined effects of MDM2 SNP 309 and p53 mutation on oral squamous cell carcinomas associated with areca quid chewing.
abstract: The recently identified single nucleotide polymorphism in the MDM2 promoter (SNP 309) may contribute to the early onset of both sporadic and hereditary malignancies in patients with defective p53. We tested this hypothesis by examining the effects of combined MDM2 polymorphisms and somatic p53 mutations on 351 oral squamous cell carcinomas (OSCCs) associated with areca quid chewing. We found that the G allele of MDM2 SNP 309 was associated with early age of onset (p=0.02) and poor differentiation of OSCC tumors (p=0.01). The frequency of lymph node extracapsular spread (LNECS) was increased in individuals having both the MDM2 SNP 309 GG genotype and p53 mutation (chi(2) for trend p=0.04). MDM2 GG genotype and p53 mutations were associated with poor disease-free survival in both early and lymph node positive advanced stage OSCC patients (Hazard ratio=2.77 and 1.93, respectively). Taken together, an interaction between MDM2 SNP 309 and p53 with respect to tumor behaviors (including disease onset, tumor differentiation, LNECS and disease-free survival) was observed in sporadic Taiwanese OSCCs.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors.forename: Shiang-Fu
authors.initials: SF
authors.lastname: Huang
authors.forename: I-How
authors.initials: IH
authors.lastname: Chen
authors.forename: Chun-Ta
authors.initials: CT
authors.lastname: Liao
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Wang
authors.forename: Saou-Hsing
authors.initials: SH
authors.lastname: Liou
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Hsieh
mesh_terms: D001114:Areca / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism
chemical_list: C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2