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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

  • Urologic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgments

This study was supported by NIH Grants U01 CA127615, R01 CA74880, P50 CA91846, R01 CA131335, and MD Anderson’s Cancer Center Support Grant CA016672.

Conflict of interest

All authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Epidemiology, Unit 1340, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Hung-Lung Ke MD, Jie Lin PhD, Yuanqing Ye PhD, Hua Wei PhD, Maosheng Huang MD, David W. Chang PhD & Xifeng Wu MD, PhD

  2. Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Colin P. Dinney MD

  3. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hung-Lung Ke MD, Wen-Jeng Wu MD, PhD & Hui-Hui Lin PhD

  4. Graduate Institute of Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hung-Lung Ke MD & Wen-Jeng Wu MD, PhD

  5. Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hung-Lung Ke MD, Wen-Jeng Wu MD, PhD & Hui-Hui Lin PhD

  6. Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan

    Wen-Jeng Wu MD, PhD

Authors
  1. Hung-Lung Ke MD
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Correspondence to Xifeng Wu MD, PhD.

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Ke, HL., Lin, J., Ye, Y. et al. 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. Ann Surg Oncol 22, 4104–4110 (2015). https://doi.org/10.1245/s10434-015-4431-5

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  • DOI: https://doi.org/10.1245/s10434-015-4431-5

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