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BIRC5 promoter SNPs do not affect nuclear survivin expression and survival of malignant pleural mesothelioma patients

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Abstract

Purpose

Malignant pleural mesothelioma is an incurable, asbestos-associated cancer. Its incidence is rapidly increasing and survival remains short. Apoptosis deregulation is an important feature of cancer and survivin, a member of the inhibitor-of-apoptosis-protein family encoded by the BIRC5 gene, has been suggested to have a role in the development and progression of several cancers. Genetic variability, in particular single nucleotide polymorphisms in the BIRC5 promoter, may affect the protein’s expression levels. The aim of our study was to elucidate the effects of BIRC5 promoter single nucleotide polymorphisms on survivin expression, patient survival and age at diagnosis in malignant pleural mesothelioma.

Methods

Archival mesothelioma samples from 101 Slovenian patients were immunohistochemically analysed for survivin expression. DNA was extracted from tumour samples and genotyped for three BIRC5 promoter single nucleotide polymorphisms (−31G > C, −241C > T and −625G > C). Genotypes were associated with nuclear survivin expression. Nuclear survivin expression, genotypes, haplotypes, histological type, gender and asbestos exposure were included in univariate Cox survival analyses.

Results

Survivin expression was detected in both tumour cell nuclei and cytoplasms in all analysed samples. No association between BIRC5 promoter polymorphism genotypes or haplotypes and nuclear survivin expression was found. Polymorphism −241C > T affected patients’ age at diagnosis. Survival analysis confirmed that younger age at diagnosis and epitheloid histological type improved survival, but no significant effects of nuclear survivin expression or genotype/haplotype on overall survival were observed.

Conclusion

Our findings indicate no relationship between BIRC5 genotypes and survivin expression or overall survival in mesothelioma patients. We observed that BIRC5 −241C > T polymorphism had a significant effect on patient age at diagnosis.

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Acknowledgments

The authors wish to thank Nada Godnič for her help with immunohistochemhistry and Jože Pižem, PhD for help with statistics. We are especially grateful to Vilijem Kovač, MD for clinical data and Maja Čemažar, PhD for her critical review of the manuscript. This work was supported by the Slovenian Research Agency (ARRS grants P3-0003 and P1-0170-0381).

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Authors and Affiliations

  1. College of Health Care Izola, University of Primorska, Polje 42, 6310, Izola, Slovenia

    Julija Hmeljak & Andrej Cör

  2. Faculty of Medicine, Institute of Biochemistry, Pharmacogenetics Laboratory, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia

    Nina Erčulj & Vita Dolžan

  3. University Clinic of Allergic and Pulmonary Disease Golnik, Golnik 36, 4204, Golnik, Slovenia

    Izidor Kern

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  1. Julija Hmeljak
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  2. Nina Erčulj
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Correspondence to Julija Hmeljak.

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Hmeljak, J., Erčulj, N., Dolžan, V. et al. BIRC5 promoter SNPs do not affect nuclear survivin expression and survival of malignant pleural mesothelioma patients. J Cancer Res Clin Oncol 137, 1641–1651 (2011). https://doi.org/10.1007/s00432-011-1030-0

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