title: Significance of MDM2-309 polymorphisms and induced corresponding plasma MDM2 levels in susceptibility to laryngeal squamous cell carcinoma.
abstract: The tumor suppressor p53 plays a crucial role in maintaining genomic stability and tumor prevention. Murine double-minute 2 (MDM2) oncoprotein plays a pivotal role in regulating p53, and the single-nucleotide polymorphism (SNP) 309T/G SNP in the promoter region of Mdm2 has been shown to be associated with increased risk of cancer. We investigated the association between Mdm2-309 promoter polymorphism, plasma MDM2 levels, and risk of laryngeal squamous cell carcinoma (LSCC). In this case-control study, 146 patients with LSCC, 61 patients with vocal leukoplakia, and 212 healthy controls were genotyped for the Mdm2-309 T/G gene using pyrosequencing. Plasma MDM2 levels were also analyzed by enzyme-linked immunosorbent assay (ELISA). Patients with LSCC had a significantly lower frequency of GT at Mdm2-309 (odds ratio [OR]=0.50, p=0.02) than controls. The proportion of GT heterozygotes in advanced stage cases were less than that in the initial stage patients (OR: 0.36 vs. 0.63; p=0.007 and 0.16). The same result was found between cases with and without lymph node metastases (OR: 0.45 vs. 0.52; p=0.075 and 0.04). Moreover, the plasma Mdm2 concentrations of LSCC patients (343.36±14.8 pg/mL) were significantly higher than those in controls (255.76±8.2 pg/mL; p<0.01) and vocal leukoplakia patients (301.42±8.6 pg/mL; p<0.05). Patients in advanced stages and with lymph node metastasis had higher plasma MDM2 levels, while the GT genotypes (308.06±18.9 pg/mL; p=0.037) had lower MDM2 plasma levels than the TT genotypes (369.00±25.2 pg/mL). The Mdm2 SNP309 G allele is implicated as an important LSCC and a vocal leukoplakia protective factor in the Chinese Han Population, and the proportion of GT genotype was lower in advanced LSCC patients and lymph node metastasis patients. Moreover, Mdm2-309 GT genotype patients had a lower plasma MDM2 level than the TT genotypes.
authors: 1 Department of Otolaryngology, Eye Ear Nose and Throat Hospital, Fudan University , Shanghai, China .
authors: Jian
authors: J
authors: Zhou
authors: Fei
authors: F
authors: Liu
authors: Duo
authors: D
authors: Zhang
authors: Bin
authors: B
authors: Chen
authors: Qing
authors: Q
authors: Li
authors: Lin
authors: L
authors: Zhou
authors: Li-Ming
authors: LM
authors: Lu
authors: Lei
authors: L
authors: Tao
mesh_terms: D000818:Animals; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics*; D016015:Logistic Models; D051379:Mice; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000097:blood* / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D017931:DNA Primers; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2