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

Our plain-English summary of The Influence of Genetic Variability on the Risk of Developing Malignant Mesothelioma, by A. Franko, N. Kotnik, K. Goricar, et al (Radiology and Oncology, 2018).

The study

• Authors: A. Franko, N. Kotnik, K. Goricar, V. Kovac, M. Dodic-Fikfak, V. Dolzan
• Journal: Radiology and Oncology
• Published: 2018;52(1):105-111
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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 NQO1, CAT, SOD2 and hOGG1 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 NQO1, CAT, SOD2 and hOGG1 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). 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).

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.

In plain English

This Slovenian study compared mesothelioma patients with asbestos-exposed controls. It asked whether variants in four genes involved in oxidative defence (NQO1, CAT, SOD2) or DNA repair (hOGG1) were linked to the disease. Cases were 159 patients treated in Ljubljana from 2007 to 2013; controls were 122 asbestos cement workers without asbestos-related disease. Unadjusted, risk was higher in smokers (odds ratio 9.30, 95% CI 4.83–17.98) and rose slightly with age (1.10, 95% CI 1.08–1.14). In the 64 patients and all controls with graded exposure (some patients graded from work histories), medium and high versus low exposure gave an odds ratio of 7.05 (95% CI 3.59–13.83). NQO1 variant carriers (CT or TT) versus CC had an unadjusted odds ratio of 1.73 (95% CI 1.02–2.96). This stayed significant after adjusting for smoking, but not for age or exposure. Other variants showed no association alone. The interaction between CAT and hOGG1 variants appeared protective (interaction odds ratio 0.27, 95% CI 0.10–0.77). No gene-asbestos interactions were found. The authors noted patients were older than controls and exposure was gradable for only some patients.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case-control genetic association study (mesothelioma cases compared with asbestos-exposed controls without disease), analysed with logistic regression
• Who was studied: 159 malignant mesothelioma patients (pleural and peritoneal) treated at the Institute of Oncology Ljubljana between March 2007 and January 2013, and 122 controls occupationally exposed to asbestos at the Salonit Anhovo asbestos cement plant, Slovenia, with no asbestos-related disease; all Central European Caucasian (Slovenian)
• Exposure: Cumulative asbestos exposure grouped as low (less than 11 fibres/cm3-years), medium (11 to 20) and high (more than 20); fiber types not specified. Smoking was also assessed. Gene polymorphisms studied: NQO1 rs1800566, CAT rs1001179, SOD2 rs4880, hOGG1 rs1052133
• Main results:
  • Smokers had higher mesothelioma risk in univariate analysis: OR 9.30 (95% CI 4.83–17.98)
  • Risk rose slightly with older age in univariate analysis: OR 1.10 (95% CI 1.08–1.14)
  • Medium and high asbestos exposure versus low exposure: OR 7.05 (95% CI 3.59–13.83). This was measured in the subgroup with gradable exposure: all 122 controls and 64 mesothelioma patients
  • Exposure could be categorized for all controls and 64 (50.8%) mesothelioma patients
  • Measured cumulative exposure data were available for 27 mesothelioma patients. For the rest, work histories were compared with patients of known exposure, and 37 were assigned to a presumed exposure group this way
  • Carriers of at least one variant NQO1 rs1800566 allele (CT and TT) had increased risk compared with CC (unadjusted): OR 1.73 (95% CI 1.02–2.96, p = 0.043)
  • The NQO1 association remained significant after adjustment for smoking. Table 2 gives OR 1.88 (95% CI 1.04–3.41, p = 0.037) for that adjustment
  • The NQO1 association was slightly lower and not statistically significant when adjusted for age (OR 1.63, 95% CI 0.91–2.95, p = 0.103) or for asbestos exposure (OR 1.72, 95% CI 0.83–3.57, p = 0.124), per Table 2
  • No association was observed between mesothelioma and the CAT, SOD2 or hOGG1 polymorphisms individually
  • The interaction between CAT rs1001179 and hOGG1 rs1052133 had a protective effect: interaction OR 0.27 (95% CI 0.10–0.77, p = 0.014)
  • No interaction was found between any of the polymorphisms and asbestos exposure
• The authors' conclusion: The authors concluded that the NQO1 polymorphism influences mesothelioma risk both independently and after adjustment for smoking. They also concluded that the protective CAT and hOGG1 interaction indicates the importance of interaction between antioxidative and DNA repair mechanisms.
• Limitations the authors state:
  • Mesothelioma patients were significantly older than controls; the authors adjusted for age in the analysis
  • Cumulative asbestos exposure could not be determined for all patients, especially for environmental or occasional exposure, so some analyses used only a subgroup of patients
  • The authors state that larger studies with well-defined asbestos exposure are needed to clarify gene-environment interactions

Topics

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Asbestos Exposure, Reactive Oxygen Species (ROS), Mechanism of Carcinogenesis, Odds Ratio, confidence interval.

Related studies

• The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesothelioma — P. Piber, N. Vavpetic, et al. (2020)
• Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseases — K. Goricar, V. Kovac, et al. (2020)
• How to Better Understand the Influence of Host Genetics on Developing an Effective Immune Response to Thoracic Cancers — K. Behrouzfar, K. Burton, et al. (2021)
• NLRP3 and CARD8 polymorphisms influence risk for asbestos-related diseases — A. Franko, K. Goricar, et al. (2020)
• The influence of genetic polymorphisms of GSTP1 on the development of asbestosis — A. Franko, V. Dolzan, et al. (2008)
• Genetic polymorphisms in aquaporin 1 as risk factors for malignant mesothelioma and biomarkers of response to cisplatin treatment — B. Senk, K. Goricar, et al. (2019)

Browse more research in Radiology and Oncology, or return to medical research.