The Influence of Genetic Variability on the Risk of Developing Malignant Mesothelioma.

BACKGROUND

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 , , and genes, gene-gene interactions and gene-environment interactions on malignant mesothelioma risk.

PATIENTS AND METHODS

In total, 150 cases with malignant mesothelioma and 122 controls with no asbestos-related disease were genotyped for , , and polymorphisms.

RESULTS

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). 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 rs1001179 or rs1052133 polymorphism and malignant mesothelioma, interaction between both polymorphisms showed a protective effect, OR 0.27 (95% CI 0.10-0.77).

CONCLUSIONS

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.