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

Overview

Journal J Cancer

Specialty Oncology

Date 2017 Aug 19

PMID 28819417

Citations 4

Authors

Christophe Deben

Ken Op de Beeck

Jolien Van den Bossche

Julie Jacobs

Filip Lardon

An Wouters

Marc Peeters

Guy Van Camp

Christian Rolfo

Vanessa Deschoolmeester

Patrick Pauwels

Affiliations

Soon will be listed here.

Abstract

Two functional polymorphisms in the 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 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 SNPs in the outcome of NSCLC patients. 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 status of the tumor. We found that the SNP285C allele, but not the SNP309G allele, was significantly associated with increased 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 (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 . 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 ) and SNP285 act as negative prognostic markers for NSCLC patients, implicating a prominent role for these variants in the outcome of these patients.

Citing Articles

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The 40bp Indel Polymorphism rs150550023 in the Promoter is Associated with Intriguing Shifts in Gene Expression in the p53-MDM2 Regulatory Hub.

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Association of the SNP285 and SNP309 Genetic Variants with the Risk, Age at Onset and Prognosis of Breast Cancer in Central European Women: A Hospital-Based Case-Control Study.

Miedl H, Lebhard J, Ehart L, Schreiber M Int J Mol Sci. 2019; 20(3).

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