The influence of genetic variability on the risk of developing malignant mesothelioma

  • Alenka Franko Clinical Institute of Occupational Medicine, University Medical Centre Ljubljana, Poljanski nasip 58, 1000 Ljubljana
  • Nika Kotnik Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana
  • Katja Goričar Pharmacogenetics Laboratory, Institute of Biochemistry Faculty of Medicine, University of Ljubljana Vrazov trg 2 SI-1000 Ljubljana
  • Viljem Kovač Institute of Oncology Ljubljana, Zaloška cesta 2, 1000 Ljubljana
  • Metoda Dodič Fikfak Clinical Institute of Occupational Medicine, University Medical Centre Ljubljana, Poljanski nasip 58, 1000 Ljubljana
  • Vita Dolžan Pharmacogenetics Laboratory, Institute of Biochemistry Faculty of Medicine, University of Ljubljana Vrazov trg 2 SI-1000 Ljubljana Slovenia http://orcid.org/0000-0001-6707-6649

Abstract

Malignant mesothelioma is a rare cancer with poor outcome, associated with asbestos exposure. Reactive oxygen species may play an important role in the mechanism of carcinogenesis; therefore, genetic variability in antioxidative defence may modify an individual's susceptibility to this cancer. This study investigated the influence of functional polymorphisms of NQO1, CAT, SOD2 and hOGG1 genes, gene-gene interactions and gene-environment interactions on malignant mesothelioma risk. In total, 150 cases with malignant mesothelioma and 122 controls with no asbestos-related disease were genotyped for NQO1, CAT, SOD2 and hOGG1 polymorphisms. The risk of malignant mesothelioma increased with smoking, odds ratio (OR) 9.30 [95% confidence interval (CI): 4.83–17.98] and slightly with age, OR 1.10 (95% CI: 1.08–1.14). Medium and high asbestos exposures represented 7-times higher risk of malignant mesothelioma compared to low exposure, OR 7.05 (95% CI 3.59–13.83). NQO1 rs1800566 was significantly associated with increased malignant mesothelioma risk, OR 1.73 (95% CI 1.02–2.96). Although there was no independent association between either CAT rs1001179 or hOGG1 rs1052133 polymorphism and malignant mesothelioma, interaction between both polymorphisms showed a protective effect, ORint 0.27 (95 % CI 0.10–0.77). Our findings suggest a role of both genetic variability in antioxidative defence and repair as well as the impact of gene-gene interactions in the development of malignant mesothelioma. The results of this study could add to our understanding of pathogenesis of malignant mesothelioma and contribute to prevention and earlier diagnosis of this aggressive cancer.

Published
2018-02-21
How to Cite
Franko, A., Kotnik, N., Goričar, K., Kovač, V., Dodič Fikfak, M., & Dolžan, V. (2018). The influence of genetic variability on the risk of developing malignant mesothelioma. Radiology and Oncology, 52(1). Retrieved from https://radioloncol.com/index.php/ro/article/view/2899
Section
Experimental oncology