Prognostic potential of the MDM2 309T>G polymorphism in stage I lung adenocarcinoma

Published on May 1, 2016in Cancer Medicine3.491
· DOI :10.1002/CAM4.750
Yasuaki Enokida5
Estimated H-index: 5
(Gunma University),
Kimihiro Shimizu33
Estimated H-index: 33
(Gunma University)
+ 13 AuthorsIzumi Takeyoshi30
Estimated H-index: 30
(Gunma University)
Sources
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.
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#1Yasuaki Enokida (Gunma University)H-Index: 5
#2Kimihiro Shimizu (Gunma University)H-Index: 33
Last. Izumi Takeyoshi (Gunma University)H-Index: 30
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Murine double minute 2 (MDM2) is a negative regulator of p53. A single-nucleotide polymorphism (SNP) (rs2279744: c.309T>G) in the promoter region of the MDM2 gene has been shown to result in higher levels of MDM2 RNA and protein. Regarding the contribution of c.309T>G in the MDM2 gene to the lung cancer risk, previous studies are conflicting. In order to evaluate the association between c.309T>G and the lung cancer risk, a case-control study was performed. The MDM2 genotypes were determined in 7...
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#2Kimihiro Shimizu (Gunma University)H-Index: 33
Last. Izumi Takeyoshi (Gunma University)H-Index: 30
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Murine double minute 2 (MDM2) is a negative regulator of the tumor suppressor gene p53. Single nucleotide polymorphisms in MDM2 and p53 can affect patient's response to chemotherapy as well as overall survival of many cancers. This study aimed to assess the associations between polymorphisms in MDM2 and p53 and survival of non-small cell lung cancer (NSCLC) patients in Chinese. We selected and genotyped both potentially functional SNPs and tagging SNPs in MDM2 and p53 using Illumina Golden Gate ...
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