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

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 can...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884639/
https://www.ncbi.nlm.nih.gov/pubmed/27228500
http://dx.doi.org/10.1002/cam4.750
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author 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
author_facet 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
author_sort Enokida, Yasuaki
collection PubMed
description 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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spelling pubmed-48846392016-08-11 Prognostic potential of the MDM2 309T>G polymorphism in stage I lung adenocarcinoma 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 Cancer Med Clinical Cancer Research 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. John Wiley and Sons Inc. 2016-05-26 /pmc/articles/PMC4884639/ /pubmed/27228500 http://dx.doi.org/10.1002/cam4.750 Text en © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Cancer Research
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
Prognostic potential of the MDM2 309T>G polymorphism in stage I lung adenocarcinoma
title Prognostic potential of the MDM2 309T>G polymorphism in stage I lung adenocarcinoma
title_full Prognostic potential of the MDM2 309T>G polymorphism in stage I lung adenocarcinoma
title_fullStr Prognostic potential of the MDM2 309T>G polymorphism in stage I lung adenocarcinoma
title_full_unstemmed Prognostic potential of the MDM2 309T>G polymorphism in stage I lung adenocarcinoma
title_short Prognostic potential of the MDM2 309T>G polymorphism in stage I lung adenocarcinoma
title_sort prognostic potential of the mdm2 309t>g polymorphism in stage i lung adenocarcinoma
topic Clinical Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884639/
https://www.ncbi.nlm.nih.gov/pubmed/27228500
http://dx.doi.org/10.1002/cam4.750
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