Genetic Variants of the MDM2 Gene Are Predictive of Treatment-Related Toxicities and Overall Survival in Patients With Advanced NSCLC.
Abstract
INTRODUCTION: Platinum agents can cause the formation of DNA adducts and induce apoptosis
to eliminate tumor cells. The aim of the present study was to investigate the influence
of genetic variants of MDM2 on chemotherapy-related toxicities and clinical outcomes
in patients with advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS:
We recruited 663 patients with advanced NSCLC who had been treated with first-line
platinum-based chemotherapy. Five tagging single nucleotide polymorphisms (SNPs) in
MDM2 were genotyped in these patients. The associations of these SNPs with clinical
toxicities and outcomes were evaluated using logistic regression and Cox regression
analyses. RESULTS: Two SNPs (rs1470383 and rs1690924) showed significant associations
with chemotherapy-related toxicities (ie, overall, hematologic, and gastrointestinal
toxicity). Compared with the wild genotype AA carriers, patients with the GG genotype
of rs1470383 had an increased risk of overall toxicity (odds ratio [OR], 3.28; 95%
confidence interval [CI], 1.34-8.02; P = .009) and hematologic toxicity (OR, 4.10;
95% CI, 1.73-9.71; P = .001). Likewise, patients with the AG genotype of rs1690924
showed more sensitivity to gastrointestinal toxicity than did those with the wild-type
homozygote GG (OR, 2.32; 95% CI, 1.30-4.14; P = .004). Stratified survival analysis
revealed significant associations between rs1470383 genotypes and overall survival
in patients without overall or hematologic toxicity (P = .007 and P = .0009, respectively).
CONCLUSION: The results of our study suggest that SNPs in MDM2 might be used to predict
the toxicities of platinum-based chemotherapy and overall survival in patients with
advanced NSCLC. Additional validations of the association are warranted.
Type
Journal articleSubject
Non–small-cell lung cancerPlatinum-based chemotherapy
Polymorphisms
Progression-free survival
Toxicity
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Non-Small-Cell Lung
Female
Genetic Variation
Humans
Logistic Models
Lung Neoplasms
Male
Middle Aged
Platinum Compounds
Polymorphism, Single Nucleotide
Proportional Hazards Models
Proto-Oncogene Proteins c-mdm2
Survival Rate
Treatment Outcome
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https://hdl.handle.net/10161/10677Published Version (Please cite this version)
10.1016/j.cllc.2015.02.001Publication Info
Qian, J; Liu, H; Gu, S; Wu, Q; Zhao, X; Wu, W; ... Lu, D (2015). Genetic Variants of the MDM2 Gene Are Predictive of Treatment-Related Toxicities and
Overall Survival in Patients With Advanced NSCLC. Clin Lung Cancer, 16(5). pp. e37-e53. 10.1016/j.cllc.2015.02.001. Retrieved from https://hdl.handle.net/10161/10677.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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