<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_raon-2018-0004_s_005_w2aab3b7c13b1b6b1aab1c18b1Aa"><h3>Background</h3><p>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 <italic>NQO1</italic>, <italic>CAT</italic>, <italic>SOD2</italic> and <italic>hOGG1</italic> genes, gene-gene interactions and gene-environment interactions on malignant mesothelioma risk.</p></sec><sec id="j_raon-2018-0004_s_006_w2aab3b7c13b1b6b1aab1c18b2Aa"><h3>Patients and methods</h3><p>In total, 150 cases with malignant mesothelioma and 122 controls with no asbestos-related disease were genotyped for <italic>NQO1</italic>, <italic>CAT</italic>, <italic>SOD2</italic> and <italic>hOGG1</italic> polymorphisms.</p></sec><sec id="j_raon-2018-0004_s_007_w2aab3b7c13b1b6b1aab1c18b3Aa"><h3>Results</h3><p>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). <italic>NQO1</italic> 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 <italic>CAT</italic> rs1001179 or <italic>hOGG1</italic> rs1052133 polymorphism and malignant mesothelioma, interaction between both polymorphisms showed a protective effect, OR<sub>int</sub> 0.27 (95% CI 0.10–0.77).</p></sec><sec id="j_raon-2018-0004_s_008_w2aab3b7c13b1b6b1aab1c18b4Aa"><h3>Conclusions</h3><p>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.</p></sec></abstract>

BackgroundMalignant 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.Patients and methodsIn total, 150 cases with malignant mesothelioma and 122 controls with no asbestos-related disease were genotyped for NQO1, CAT, SOD2 and hOGG1 polymorphisms.ResultsThe 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).ConclusionsOur 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.

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

Radiology and Oncology

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BackgroundMalignant mesothelioma is a rare cancer with poor outcome, associated with asbestos exposure. Reactive oxygen species may play an important role in...

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

Article Category: Research Article

Publicado en línea: 24 ene 2018

Páginas: 105 - 111

Recibido: 03 sept 2017

Aceptado: 12 sept 2017

DOI: https://doi.org/10.2478/raon-2018-0004

© 2018 Alenka Franko, Nika Kotnik, Katja Goricar, Viljem Kovac, Metoda Dodic-Fikfak, Vita Dolzan

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.