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Impact of BCL2 polymorphisms on survival in transitional cell carcinoma of the bladder

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the impact of three BCL2 single-nucleotide polymorphisms, i.e., c.−938C>A (rs2279115), c.21G>A (rs1801018), and c.*2203A>G (rs4987853) on survival in patients with transitional cell carcinoma of the bladder.

Methods

We analyzed 179 patients who underwent surgical treatment for bladder cancer at the Clinic of Urology, University Hospital Essen, Germany. Genomic DNA was extracted and genotyped for the polymorphisms. For all polymorphisms, linkage analysis was performed. Kaplan–Meier and Cox regression analyses were used to determine the putative impact of the three polymorphisms on outcome.

Results

c.−938C>A and c.21G>A, but not c.*2203A>G, are in strong linkage disequilibrium (D′ 0.96). We found a significant association between c.−938C>A and relapse-free survival (p = 0.024) with an allele dose effect. In the same way, c.21G>A had a significant impact on both relapse-free survival (p = 0.009) and progression-free survival (p = 0.012), as well as a pronounced allele dose effect. Regression analysis proved c.21G>A and c.−938C>A, to be an independent risk factor in univariate and multivariable analyses.

Conclusions

In our cohort, both c.−938C>A and c.21G>A showed a significant impact on outcome with TCC of the bladder. Due to the linkage disequilibrium of both SNPs, maybe, only one of them could mediate this effect. In multivariable analysis, however, both proved to be independently associated with overall survival. Contrary to other findings which found the c.−938C>A mainly influencing outcome, our data may suggest that the main effect on TCC could be due to the c.21G>A polymorphism.

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Authors and Affiliations

  1. Clinic of Urology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany

    Jochen Hess & Herbert Rübben

  2. Institute of Pharmacogenetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    Jochen Hess, Patrick Stelmach & Hagen Sjard Bachmann

  3. Praxisklinik Urologie Rhein/Ruhr, Mülheim, Germany

    Andreas Eisenhardt

  4. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    Henning Reis & Kurt Werner Schmid

Authors
  1. Jochen Hess
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  2. Patrick Stelmach
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  3. Andreas Eisenhardt
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  4. Herbert Rübben
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  5. Henning Reis
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  6. Kurt Werner Schmid
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  7. Hagen Sjard Bachmann
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Correspondence to Jochen Hess.

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Funding

This research work was funded by an internal research grant of the University Hospital Essen (Interne Forschungsförderung Essen, IFORES).

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This study was conducted in accordance to the Declaration of Helsinki and its later amendments and approved by the local Ethics Committee of the University Hospital Essen.

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Informed consent was obtained from participants included in this study.

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Hess, J., Stelmach, P., Eisenhardt, A. et al. Impact of BCL2 polymorphisms on survival in transitional cell carcinoma of the bladder. J Cancer Res Clin Oncol 143, 1659–1670 (2017). https://doi.org/10.1007/s00432-017-2404-8

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  • DOI: https://doi.org/10.1007/s00432-017-2404-8

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