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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 12/2015

01-11-2015 | Urologic Oncology

Genetic Variations in Glutathione Pathway Genes Predict Cancer Recurrence in Patients Treated with Transurethral Resection and Bacillus Calmette–Guerin Instillation for Non-muscle Invasive Bladder Cancer

Authors: Hung-Lung Ke, MD, Jie Lin, PhD, Yuanqing Ye, PhD, Wen-Jeng Wu, MD, PhD, Hui-Hui Lin, PhD, Hua Wei, PhD, Maosheng Huang, MD, David W. Chang, PhD, Colin P. Dinney, MD, Xifeng Wu, MD, PhD

Published in: Annals of Surgical Oncology | Issue 12/2015

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Abstract

Background

Glutathione (GSH) is an important molecule involved in cell detoxification and antioxidation and may affect cancer development or outcome. We hypothesized that genetic variation in the GSH pathway might influence the clinical outcome of patients who have non-muscle invasive bladder cancer (NMIBC).

Methods

A total of 114 single nucleotide polymorphisms (SNPs) in 21 GSH pathway genes were genotyped in 414 NMIBC patients treated with transurethral resection alone (TUR) and both TUR and intravesical bacillus Calmette–Guérin instillation (BCG) therapy. The effect of each SNP on time to recurrence was estimated using the multivariate Cox proportional hazards model. Cumulative effect and survival tree analyses were performed to determine the joint effects of unfavorable genotypes and gene–gene interactions on bladder cancer prognosis.

Results

Seven SNPs showed significant associations with cancer recurrence in the TUR group and 15 SNPs showed significant associations with recurrence in the BCG group. The most significant SNP in the TUR group was rs3746162 in GPX4, whose variant genotype conferred a 5.4-fold increased risk of recurrence compared with wild-type (hazard ratio [HR] = 5.43, 95 % confidence interval [CI] = 2.19–13.46), whereas the most significant SNP in the BCG group was rs7265992 in GSS (HR 3.43, 95 % CI 1.56–7.56). The risk of recurrence increased with the number of unfavorable genotypes in both groups. Within treatment group, stratified analyses by tumor grade also indicated predictive variants.

Conclusions

Genetic variants in GSH pathway may influence cancer recurrence in NMIBC patients receiving curative treatment.
Appendix
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Metadata
Title
Genetic Variations in Glutathione Pathway Genes Predict Cancer Recurrence in Patients Treated with Transurethral Resection and Bacillus Calmette–Guerin Instillation for Non-muscle Invasive Bladder Cancer
Authors
Hung-Lung Ke, MD
Jie Lin, PhD
Yuanqing Ye, PhD
Wen-Jeng Wu, MD, PhD
Hui-Hui Lin, PhD
Hua Wei, PhD
Maosheng Huang, MD
David W. Chang, PhD
Colin P. Dinney, MD
Xifeng Wu, MD, PhD
Publication date
01-11-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 12/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4431-5

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