PMID- 24325471 OWN - NLM STAT- MEDLINE DCOM- 20140404 LR - 20221207 IS - 1557-7430 (Electronic) IS - 1044-5498 (Linking) VI - 33 IP - 2 DP - 2014 Feb TI - Significance of MDM2-309 polymorphisms and induced corresponding plasma MDM2 levels in susceptibility to laryngeal squamous cell carcinoma. PG - 88-94 LID - 10.1089/dna.2013.2220 [doi] AB - 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. FAU - Zhou, Jian AU - Zhou J AD - 1 Department of Otolaryngology, Eye Ear Nose and Throat Hospital, Fudan University , Shanghai, China . FAU - Liu, Fei AU - Liu F FAU - Zhang, Duo AU - Zhang D FAU - Chen, Bin AU - Chen B FAU - Li, Qing AU - Li Q FAU - Zhou, Lin AU - Zhou L FAU - Lu, Li-Ming AU - Lu LM FAU - Tao, Lei AU - Tao L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131210 PL - United States TA - DNA Cell Biol JT - DNA and cell biology JID - 9004522 RN - 0 (DNA Primers) RN - 0 (Tumor Suppressor Protein p53) RN - EC 2.3.2.27 (MDM2 protein, human) RN - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) SB - IM MH - Animals MH - Asian People/*genetics MH - Base Sequence MH - Carcinoma, Squamous Cell/*genetics MH - Case-Control Studies MH - DNA Primers/genetics MH - Enzyme-Linked Immunosorbent Assay MH - Genetic Predisposition to Disease/*genetics MH - Genotype MH - Humans MH - Laryngeal Neoplasms/*genetics MH - Logistic Models MH - Mice MH - Molecular Sequence Data MH - Neoplasm Metastasis/genetics MH - Odds Ratio MH - Polymorphism, Single Nucleotide/*genetics MH - Proto-Oncogene Proteins c-mdm2/*blood/*genetics MH - Sequence Analysis, DNA MH - Tumor Suppressor Protein p53/metabolism EDAT- 2013/12/12 06:00 MHDA- 2014/04/05 06:00 CRDT- 2013/12/12 06:00 PHST- 2013/12/12 06:00 [entrez] PHST- 2013/12/12 06:00 [pubmed] PHST- 2014/04/05 06:00 [medline] AID - 10.1089/dna.2013.2220 [doi] PST - ppublish SO - DNA Cell Biol. 2014 Feb;33(2):88-94. doi: 10.1089/dna.2013.2220. Epub 2013 Dec 10.