Open AccessPrognostic potential of the MDM 2 309T>G polymorphism in stage I lung adenocarcinoma
Author(s) -
Enokida Yasuaki,
Shimizu Kimihiro,
Atsumi Jun,
Kakegawa Seiichi,
Takase Yoshiaki,
Kaira Kyoichi,
Yashima Hideaki,
Araki Takuya,
Nakazawa Seshiru,
Ohtaki Yoichi,
Nagashima Toshiteru,
Alexander Lezhava,
Usui Kengo,
Ishikawa Toshihisa,
Hayashizaki Yoshihide,
Takeyoshi Izumi
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.750
Subject(s) - genotype , medicine , hazard ratio , lung cancer , kras , oncology , adenocarcinoma , genotyping , confidence interval , proportional hazards model , biology , mdm2 , gastroenterology , cancer , apoptosis , genetics , colorectal cancer , gene
The MDM 2 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 MDM 2 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 MDM 2 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 MDM 2 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 MDM 2 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 MDM 2 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.