Polymorphisms of p53 and MDM2 genes are associated with severe toxicities in patients with non-small cell lung cancer

Zheng, Datong; Chen, Yanping; Gao, Caijie; Wei, Yongyue; Cao, Guochun; Lu, Nan; Hou, Yayi; Jiang, Xiuqin; Wang, Jianjun

doi:10.4161/15384047.2014.956599

Cited by 17 publications

(17 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Zheng et al found the G allele of the MDM2 309T/G polymorphism was associated with grade 3 or 4 hematologic and overall toxicity in advanced NSCLC patients with platinum‐based chemotherapy. [Zheng et al, ]. Similarly, Park et al have found the MDM2 309G alleles increased the risk of lung adenocarcinoma [Sun et al, ].…”

Section: Discussionmentioning

confidence: 96%

Mutations in apoptotic genes and micronucleus occurrence in vinyl chloride‐exposed workers in China

Feng

Zheng

Hao

et al. 2016

Environ and Mol Mutagen

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 96%

Mutations in apoptotic genes and micronucleus occurrence in vinyl chloride‐exposed workers in China

Feng

Zheng

Hao

et al. 2016

Environ and Mol Mutagen

View full text Add to dashboard Cite

show abstract

“…45,46 However, for advanced NSCLC, the prognostic effect of this SNP remains controversial. 18,[47][48][49][50] Three studies had reported a significant association between SNP T309G and unfavorable survival in patients with advanced NSCLC, 47,48 but 2 other studies did not support the association. 49,50 Based on the results of its high LD SNP rs3730581, our study results were was consistent with those from the latter study.…”

Section: Discussionmentioning

confidence: 99%

“…The association between the functional SNP T309G (rs2279744) and platinum-based or noneplatinum-based chemotherapy responses has been investigated in many cancers. 18,35,[40][41][42][43] However, the results have been inconsistent regarding the effects of this SNP on gastrointestinal and hematologic toxicities. No significant effects were found in 136 patients with bladder cancer who received combined cisplatinbased systemic chemotherapy and radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…35 One recent study observed a significant association between severe hematologic and overall toxicities and SNP309 in 444 patients with advanced NSCLC treated with platinum-based chemotherapy. 18 Although this SNP was not included in our study, one of its high LD SNP rs3730581 (pairwise LD r 2 ¼ 0.86), had been investigated but did not show a significant effect on any chemotherapy toxicity. That study also found that the GC heterozygotes of another functional SNP rs937282 had a greater incidence of severe gastrointestinal toxicity than did the homozygotes.…”

Section: Discussionmentioning

confidence: 99%

“…[14][15][16] However, until now, few studies have investigated the effect of MDM2 SNPs on chemotherapy toxicity. 17,18 In the present study, we selected 5…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Genetic Variants of the MDM2 Gene Are Predictive of Treatment-Related Toxicities and Overall Survival in Patients With Advanced NSCLC

Qian

Liu

et al. 2015

Clinical Lung Cancer

View full text Add to dashboard Cite

We investigated the association of 5 tagging single nucleotide polymorphisms (SNPs) of MDM2 with chemotherapy-related toxicities and clinical outcomes in 663 patients with advanced nonesmall-cell lung cancer. We identified 2 SNPs (rs1470383 and rs1690924) with significant associations with chemotherapyrelated toxicities. One SNP rs1470383 also influenced the overall survival of patients without overall toxicity or hematologic toxicity. 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 nonesmall-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 ¼ .009) and hematologic toxicity (OR, 4.10; 95% CI, 1.73-9.71; P ¼ .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 ¼ .004). Stratified survival analysis revealed significant associations between rs1470383 genotypes and overall survival in patients without overall or hematologic toxicity (P ¼ .007 and P ¼ .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.

show abstract

Genotyping Technologies in Pharmacogenomics

Zou

Sheng

Feng

et al. 2020

Pharmacogenomics in Precision Medicine

View full text Add to dashboard Cite

Polymorphisms of p53 and MDM2 genes are associated with severe toxicities in patients with non-small cell lung cancer

Cited by 17 publications

References 35 publications

Mutations in apoptotic genes and micronucleus occurrence in vinyl chloride‐exposed workers in China

Mutations in apoptotic genes and micronucleus occurrence in vinyl chloride‐exposed workers in China

Genetic Variants of the MDM2 Gene Are Predictive of Treatment-Related Toxicities and Overall Survival in Patients With Advanced NSCLC

Genotyping Technologies in Pharmacogenomics

Contact Info

Product

Resources

About