The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesothelioma

Our plain-English summary of The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesothelioma, by P. Piber, N. Vavpetic, K. Goricar, et al (Radiology and Oncology, 2020).

The study

• Authors: P. Piber, N. Vavpetic, K. Goricar, V. Dolzan, V. Kovac, A. Franko
• Journal: Radiology and Oncology
• Published: 2020;54(4):429-436
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background Asbestos exposure is associated with the development of pleural plaques as well as malignant mesothelioma (MM). Asbestos fibres activate macrophages, leading to the release of inflammatory mediators including interleukin 1 beta (IL-1β). The expression of IL-1β may be influenced by genetic variability of IL1B gene or regulatory microRNAs (miRNAs). This study investigated the effect of polymorphisms in IL1B and MIR146A genes on the risk of developing pleural plaques and MM. Subjects and methods In total, 394 patients with pleural plaques, 277 patients with MM, and 175 healthy control subjects were genotyped for IL1B and MIR146A polymorphisms. Logistic regression was used in statistical analysis. Results We found no association between MIR146A and IL1B genotypes, and the risk of pleural plaques. MIR146A rs2910164 was significantly associated with a decreased risk of MM (OR = 0.31, 95% CI = 0.13-0.73, p = 0.008). Carriers of two polymorphic alleles had a lower risk of developing MM, even after adjustment for gender and age (OR = 0.34, 95% CI = 0.14-0.85, p = 0.020). Among patients with known asbestos exposure, carriers of at least one polymorphic IL1B rs1143623 allele also had a lower risk of MM in multivariable analysis (OR = 0.50, 95% CI = 0.28-0.92, p = 0.025). The interaction between IL1B rs1143623 and IL1B rs1071676 was significantly associated with an increased risk of MM (p = 0.050). Conclusions Our findings suggest that genetic variability of inflammatory mediator IL-1β could contribute to the risk of developing MM, but not pleural plaques.

In plain English

This retrospective case-control study from Slovenia asked whether variations in two inflammation-related genes, IL1B and MIR146A, were linked to pleural plaques or malignant mesothelioma (MM). It compared 277 patients with pleural or peritoneal MM treated at the Institute of Oncology Ljubljana, 394 patients with pleural plaques and 175 healthy controls. All had been exposed to asbestos, and the plaque patients and controls had worked at the Salonit Anhovo factory. None of the four gene variants was significantly linked to pleural plaques. People with two copies of the polymorphic C form of MIR146A rs2910164 (genotype CC) had lower odds of MM than controls (odds ratio 0.31, 95% CI 0.13–0.73). This was not statistically significant after adjusting for asbestos exposure in the smaller group with exposure data (OR 0.39, 95% CI 0.11–1.38). In that group, carriers of at least one polymorphic IL1B rs1143623 allele had lower odds of MM than controls (OR 0.50, 95% CI 0.28–0.92). The authors concluded the variants may contribute to MM risk and called for confirmation in other patient groups. They named missing exposure data as a limitation.

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: Retrospective case-control genetic association study, analysed with logistic regression
• Who was studied: 277 patients with histologically confirmed pleural or peritoneal malignant mesothelioma treated at the Institute of Oncology Ljubljana between 1 January 2001 and 30 September 2018, 394 patients with pleural plaques and 175 healthy controls, all previously exposed to asbestos. The plaque patients and controls had been occupationally exposed at the Salonit Anhovo factory in Slovenia and were presented at the State Board for the Recognition of Occupational Asbestos Diseases between January 1999 and December 2003. In 2018 the controls were found not to have any asbestos-related disease.
• Exposure: The main factor studied was genetic: three IL1B variants (rs1143623, rs16944, rs1071676) and one MIR146A variant (rs2910164). Cumulative asbestos exposure was assessed semiquantitatively and grouped as low (less than 11 fibres/cm3-years), medium (11–20) or high (more than 20). These data were available for all controls, all plaque patients except 6, and 40 MM patients. For 49 more MM patients, exposure was estimated from an expert work-history interview. For the remaining 188 MM patients, exact exposure data were not available. The article does not name the fiber types.
• Main results:
  • Comparing pleural plaque patients with healthy controls, none of the selected polymorphisms had a statistically significant influence on the risk of pleural plaques, either unadjusted or after adjustment for age, gender and asbestos exposure.
  • MM patients compared with controls: carriers of MIR146A rs2910164 genotype CC (17 of 175 controls, 9.7%; 9 of 277 MM patients, 3.2%) had a lower risk of MM, OR 0.31 (95% CI 0.13–0.73, p = 0.008). After adjustment for age and gender the OR was 0.34 (95% CI 0.14–0.85, p = 0.020).
  • In the subgroup with asbestos exposure data, MIR146A rs2910164 was no longer statistically significantly associated with MM risk compared with controls after adjustment for age, gender and asbestos exposure: OR 0.39 (95% CI 0.11–1.38, p = 0.144).
  • Carriers of at least one polymorphic IL1B rs1143623 allele (genotype GC or CC) had a significantly decreased risk of MM compared with controls after adjustment for age, gender and asbestos exposure: OR 0.50 (95% CI 0.28–0.92, p = 0.025).
  • MM patients compared with pleural plaque patients: MIR146A rs2910164 genotype CC was associated with a decreased risk of MM, OR 0.32 (95% CI 0.15–0.68, p = 0.003). After adjustment for gender and age the OR was 0.33 (95% CI 0.15–0.75, p = 0.008). In the subgroup with exposure data it was significant only in the dominant model, OR 0.59 (95% CI 0.36–0.99, p = 0.046).
  • With pleural plaque patients as the comparison group, and after adjustment for age, gender and asbestos exposure, IL1B rs1071676 CC homozygotes had an increased risk of MM: OR 2.83 (95% CI 1.04–7.71, p = 0.042).
  • The interaction between IL1B rs1143623 and IL1B rs1071676 was associated with an increased MM risk: OR 2.24 (95% CI 1.00–5.00, p = 0.050). Interactions between polymorphisms showed no significant influence on the risk of pleural plaques.
  • Among subjects with known exposure, medium or high asbestos exposure was more common in MM patients (51.7%) than in controls (23.4%) or pleural plaque patients (28.4%). Medium and high exposure were associated with increased MM risk compared with controls (OR 3.50, 95% CI 2.03–6.02) and compared with pleural plaque patients (OR 2.70, 95% CI 1.69–4.33).
  • MM patients were significantly older than the other groups: median age 66.0 for MM patients, 55.3 for controls and 54.9 for pleural plaque patients. The groups did not differ significantly in gender (p = 0.410) or smoking status (p = 0.267).
• The authors' conclusion: The authors concluded that IL1B and MIR146A polymorphisms may contribute to the risk of developing MM, but not pleural plaques. They said further studies are needed to confirm these associations in independent patient cohorts.
• Limitations the authors state:
  • Asbestos exposure information was not available for all subjects, so the subgroup analysed with adjustment for asbestos exposure was smaller than the overall sample.
  • The authors said the smaller subgroup could account for the differences between the results adjusted for asbestos exposure and the unadjusted results.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Pleural Plaques, Malignant Mesothelioma, Asbestos Exposure, Macrophage.

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