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

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.

Asbestos-Related Pleural Diseases: The Role of Gene-Environment Interactions

“…No association was also found between SOD2 and CAT polymorphisms and the malignant mesothelioma risk in a study that included 159 Slovenian malignant mesothelioma patients and 122 controls. All the controls were occupationally exposed to asbestos in the asbestos-cement manufacturing plant but did not develop any disease associated with asbestos exposure [102]. However, this study reported an association between NAD(P)H quinone dehydrogenase 1 (NQO1) rs1800566 (p.Pro187Ser) SNP and malignant mesothelioma risk.…”

“…NQO1 catalyses the reduction of quinones to hydroquinones, thus preventing the formation of free radicals. The carriers of at least one polymorphic NQO1 allele (CT and TT genotypes) had an increased risk of malignant mesothelioma compared to carriers of homozygous wild-type CC genotype [102].…”

Inflammation Markers in the Evolution of Asbestosis

“…[9] Both asbestos related diseases and smoking addition show genetic influence. [10,11] In what concerns asbestosis, the development of lung fibrosis is associated with the nodd like receptor 3 (NLRP3) rs35829419 variant allele, while the transforming growth factor (TGFB1) rs2241718 variant allele with decreased risk [12]. Smoking induced lung fibrosis has similar radiological findings with asbestosis, although the histology is distinguished: the characteristic pattern of asbestosis is the initial localization of fibrosis in the bronchiolar wall and peribronchiolar area of the subpleural region of the lung and the presence of the asbestos bodies; fibrosis progressively extends into alveoli, further from the bronchiole.…”

NLRP3 and CARD8 polymorphisms influence risk for asbestos-related diseases

“…It has been suggested that in addition to asbestos exposure, genetic factors may also affect the development of asbestos-related diseases (40)(41)(42). This study investigated the influence of NLRP3 rs35829419 and CARD8 rs2043211 polymorphisms on the risk of different asbestos-related diseases.…”

“…Based on these data, the subjects were divided into three groups: low (< 11 fibres/cm 3 -years), medium (11-20 fibres/ cm 3 -years) and high (> 20 fibres/cm 3 -years) asbestos exposure. For patients with MM with no cumulative asbestos exposure data, accurate work history was obtained, and their asbestos exposures were compared with exposures of the group of subjects with known cumulative asbestos exposure and were accordingly divided into three groups with presumed low, medium and high asbestos exposure, as previously described (40). Reliable semi-quantitative data on asbestos exposure could be obtained only for 81 MM patients.…”