<i>MDM2</i> SNP309 and SNP285 Act as Negative Prognostic Markers for Non-small Cell Lung Cancer Adenocarcinoma Patients

Deben, Christophe; Op de Beeck, Ken; Van den Bossche, Jolien; Jacobs, Julie; Lardon, Filip; Wouters, An; Peeters, Marc; Van Camp, Guy; Rolfo, Christian; Deschoolmeester, Vanessa; Pauwels, Patrick

doi:10.7150/jca.19254



International Journal of Biological Sciences

International Journal of Medical Sciences

Theranostics

Journal of Genomics

Nanotheranostics

Global reach, higher impact

Full Text | PDF

J Cancer 2017; 8(12):2154-2162. doi:10.7150/jca.19254 This issue Cite

Research Paper

MDM2 SNP309 and SNP285 Act as Negative Prognostic Markers for Non-small Cell Lung Cancer Adenocarcinoma Patients

Christophe Deben^{1, 2✉}, Ken Op de Beeck^{1, 4}, Jolien Van den Bossche¹, Julie Jacobs^{1, 2}, Filip Lardon¹, An Wouters¹, Marc Peeters^{1, 3}, Guy Van Camp^{1, 4}, Christian Rolfo^{3, 5}, Vanessa Deschoolmeester^{1, 2*}, Patrick Pauwels^{1, 2*}

1. Center for Oncological Research (CORE), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium;
2. Department of Pathology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Antwerp, Belgium;
3. Department of Medical Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Antwerp, Belgium;
4. Center of Medical Genetics, University of Antwerp & Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Antwerp, Belgium;
5. Phase-1 Early Clinical Trials Unit, Antwerp University Hospital Wilrijkstraat 10, 2650 Edegem, Antwerp, Belgium.
* These authors are co-senior authors

Citation:

Deben C, Op de Beeck K, Van den Bossche J, Jacobs J, Lardon F, Wouters A, Peeters M, Van Camp G, Rolfo C, Deschoolmeester V, Pauwels P. MDM2 SNP309 and SNP285 Act as Negative Prognostic Markers for Non-small Cell Lung Cancer Adenocarcinoma Patients. J Cancer 2017; 8(12):2154-2162. doi:10.7150/jca.19254. https://www.jcancer.org/v08p2154.htm

Other styles

Abstract

Objectives: Two functional polymorphisms in the MDM2 promoter region, SNP309T>G and SNP285G>C, have been shown to impact MDM2 expression and cancer risk. Currently available data on the prognostic value of MDM2 SNP309 in non-small cell lung cancer (NSCLC) is contradictory and unavailable for SNP285. The goal of this study was to clarify the role of these MDM2 SNPs in the outcome of NSCLC patients.

Materials and Methods: In this study we genotyped SNP309 and SNP285 in 98 NSCLC adenocarcinoma patients and determined MDM2 mRNA and protein levels. In addition, we assessed the prognostic value of these common SNPs on overall and progression free survival, taking into account the TP53 status of the tumor.

Results and Conclusion: We found that the SNP285C allele, but not the SNP309G allele, was significantly associated with increased MDM2 mRNA expression levels (p = 0.025). However, we did not observe an association with MDM2 protein levels for SNP285. The SNP309G allele was significantly associated with the presence of wild type TP53 (p = 0.047) and showed a strong trend towards increased MDM2 protein levels (p = 0.068). In addition, patients harboring the SNP309G allele showed a worse overall survival, but only in the presence of wild type TP53. The SNP285C allele was significantly associated with an early age of diagnosis and metastasis. Additionally, the SNP285C allele acted as an independent predictor for worse progression free survival (HR = 3.97; 95% CI = 1.51 - 10.42; p = 0.005).

Our data showed that both SNP309 (in the presence of wild type TP53) and SNP285 act as negative prognostic markers for NSCLC patients, implicating a prominent role for these variants in the outcome of these patients.

Keywords: MDM2, SNP309, SNP285, NSCLC, Prognostic.

Citation styles

APA

Deben, C., Op de Beeck, K., Van den Bossche, J., Jacobs, J., Lardon, F., Wouters, A., Peeters, M., Van Camp, G., Rolfo, C., Deschoolmeester, V., Pauwels, P. (2017). MDM2 SNP309 and SNP285 Act as Negative Prognostic Markers for Non-small Cell Lung Cancer Adenocarcinoma Patients. Journal of Cancer, 8(12), 2154-2162. https://doi.org/10.7150/jca.19254.

ACS

Deben, C.; Op de Beeck, K.; Van den Bossche, J.; Jacobs, J.; Lardon, F.; Wouters, A.; Peeters, M.; Van Camp, G.; Rolfo, C.; Deschoolmeester, V.; Pauwels, P. MDM2 SNP309 and SNP285 Act as Negative Prognostic Markers for Non-small Cell Lung Cancer Adenocarcinoma Patients. J. Cancer 2017, 8 (12), 2154-2162. DOI: 10.7150/jca.19254.

NLM

CSE

Deben C, Op de Beeck K, Van den Bossche J, Jacobs J, Lardon F, Wouters A, Peeters M, Van Camp G, Rolfo C, Deschoolmeester V, Pauwels P. 2017. MDM2 SNP309 and SNP285 Act as Negative Prognostic Markers for Non-small Cell Lung Cancer Adenocarcinoma Patients. J Cancer. 8(12):2154-2162.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.