title: Prognostic potential of the MDM2 309T>G polymorphism in stage I lung adenocarcinoma.
abstract: The MDM2 protein plays an important role in the regulation of cell proliferation and apoptosis via ubiquitination and proteasome-mediated degradation of p53. The genetic polymorphism rs2279744 (c.309T>G) of the MDM2 gene is reportedly associated with susceptibility and/or prognosis in various cancers. In this study, we investigated the risk factors for worse survival in patients with lung adenocarcinoma (AC). We examined the association between c.309T>G and the prognosis of lung cancer by retrospectively reviewing 453 lung cancer patients. We studied both, clinicopathological and genetic characteristics, including the c.309T>G, p53 Arg72Pro, EGFR, KRAS, and p53 mutations. Associations between these factors and survival outcome were analyzed using Cox proportional hazards models. The frequencies of MDM2 polymorphisms were T/T, 20.8%; T/G, 48.6%, and G/G, 30.7%. The overall survival (OS) of AC patients with pathological stage I disease and the MDM2 T/T genotype was significantly shorter than that of those with the T/G or G/G genotypes (P = 0.02). Multivariate analysis revealed that the MDM2 T/T genotype was an independent, significant prognostic factor (hazard ratio [HR] = 2.23; 95% confidence interval [CI]: 1.07-4.65; P = 0.03). The MDM2 T/T genotype was predictive of poorer survival in a Japanese population. Genotyping for this polymorphism might predict the clinical outcomes of stage I AC patients.
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Enokida
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Atsumi
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kakegawa
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takase
authors.affiliation: Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kaira
authors.affiliation: Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yashima
authors.affiliation: Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Araki
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Seshiru
authors.initials: S
authors.lastname: Nakazawa
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ohtaki
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Toshiteru
authors.initials: T
authors.lastname: Nagashima
authors.affiliation: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Lezhava
authors.initials: L
authors.lastname: Alexander
authors.affiliation: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Usui
authors.affiliation: NGO Personalized Medicine & Healthcare, Yokohama, Kanagawa, 226-0016, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: RIKEN Preventive Medicine and Diagnosis Innovation Program, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Takeyoshi
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011013:Pneumonectomy / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Lung cancer; MDM2; SNP; SNP309; p53; polymorphism; prognosis