Polymorphisms in Translesion Polymerase Genes Influence Treatment Outcome in Malignant Mesothelioma

Abstract

Aim: We evaluated the influence of genetic variability in translesion polymerases REV1 and REV3L on the outcome of cisplatin treatment in malignant mesothelioma patients. Materials & methods: In total, 139 malignant mesothelioma patients were genotyped for seven tag SNPs in REV1 and REV3L. Logistic regression and Cox regression were used to assess the influence of SNPs on treatment outcome. Results: Polymorphic REV1 rs3087403 allele and REV1 TGT haplotype were associated with increased risk for leukopenia (p = 0.013 and p = 0.047, respectively) and neutropenia (p = 0.048 and p = 0.024, respectively). REV3L rs465646, rs462779 and REV3L CCGG haplotype were significantly associated with longer overall survival (p = 0.007, p = 0.022 and p = 0.013, respectively). Conclusion: Our results suggest for the first time that REV1 and REV3L SNPs might serve as potential predictive markers of outcome of cisplatin-based chemotherapy.

Original submitted 7 October 2013; Revision submitted 15 January 2014

Keywords::

• cisplatin
• mesothelioma
• polymorphism
• REV1
• REV3L

Acknowledgements

The authors thank B Možina, Head of the Biochemistry Laboratory, Institute of Oncology Ljubljana, Slovenia, for her help with blood sample collections and handling. The authors also wish to acknowledge N Erčulj for the initial help with data acquisition. The authors thank the staff from the University Clinic of Allergic and Pulmonary Disease Golnik, Slovenia, for their help with diagnosis and treatment of malignant mesothelioma patients: I Kern for performing the histopathological diagnosis; A Debeljak, A Rozman, M Torel and A Crnjac for performing the invasive diagnostic procedures and T Čufer and N Triller for providing first-line treatment for one patient each. The authors are also grateful to the team for lung cancer treatment at the Institute of Oncology Ljubljana, Slovenia, for their help with patient treatment.

Financial & competing interests disclosure

This work was financially supported by The Slovenian Research Agency (Grants L3-3648 and P1-0170). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was financially supported by The Slovenian Research Agency (Grants L3-3648 and P1-0170). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.