Interleukin gene polymorphisms in pneumoconiosis

Our plain-English summary of Interleukin gene polymorphisms in pneumoconiosis, by S. Helmig, M. Grossmann, J. Wübbeling, et al (International Journal of Molecular Medicine, 2012).

The study

• Authors: S. Helmig, M. Grossmann, J. Wübbeling, J. Schneider
• Journal: International Journal of Molecular Medicine
• Published: 2012;30(2):401-8
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Inhaled asbestos fibres are known to cause inflammation processes with the result of lung or pleural fibrosis and malignancies. Interleukins (IL), such as IL-1β, IL-6 and IL-10, have various functions in the regulation of the inflammatory response and in proliferative processes after inhalation of silica dust and can, therefore, influence the pathogenesis of asbestos-induced fibrosis and carcinogenesis. Polymorphisms within these genes may be associated with susceptibility to silica and asbestos-induced lung diseases. Thus, IL-1β, IL-6 and IL-10 polymorphisms were examined to determine an association with asbestos or silica-induced fibrosis or malignancies. Association studies were performed in 1180 individuals, using control subjects (n=177), fibrosis patients (n=605), lung cancer (LC) patients (n=364) and malignant mesothelioma (MM) patients (n=34). IL-1β (C-511T; C+3954T), IL-6 (G-174C) as well as IL-10 (G-1082A) polymorphisms were investigated. Compared to a healthy (control) group, a higher risk was seen for malignant mesothelioma patients in all investigated polymorphisms. The IL-6 -174C allele showed a tendency towards a higher risk for fibrosis or asbestos-induced lung cancer (ORasbestosis, 1.338; 95% CI, 0.71-2.53; ORsilicosis, 1.226; 95% CI, 0.54-2.81; ORfibrosis other aetiology, 1.313; 95% CI, 0.58-2.98 and ORLC asbestos, 2.112; 95% CI, 0.75-5.92). The IL-10 -1082A carrier seemed to be at higher risk for silicosis (ORsilicosis, 2.064; 95% CI, 0.78-5.49) but not for asbestosis. In summary, this study did not reveal sufficient evidence for a significant association of the investigated interleukin polymorphisms with asbestos or silica-induced diseases in the population studied.

In plain English

This German case-control study asked whether common variants in three immune-signalling genes were associated with asbestos- or silica-induced fibrosis or malignancies. The variants were two in IL-1β, one in IL-6 and one in IL-10. The authors tested blood DNA from 1180 people. These were 177 healthy controls with no workplace exposure to carcinogenic or fibrogenic agents, 605 lung fibrosis patients (389 asbestosis, 161 silicosis, 55 other cause), 364 lung cancer patients (49 asbestos-related) and 34 diffuse malignant mesothelioma patients. Asbestos fiber types were not specified. Odds ratios were adjusted for age, gender and smoking pack years. For mesothelioma patients, the authors reported higher risk estimates for all four variants, for example 1.918 (95% CI 0.68 to 5.45) for IL-6 C-allele carriers. IL-6 C-allele carriers with asbestos-related lung cancer had an odds ratio of 2.112 (0.75 to 5.92). None of these results reached statistical significance. The authors concluded the study did not reveal sufficient evidence for an association of these variants with asbestos- or silica-induced diseases. They suggested a single variant may have too little effect to show significance.

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 comparing gene variant frequencies in patient groups with a non-exposed healthy control group, using logistic regression adjusted for age, gender and smoking pack years
• Who was studied: 1180 German individuals. There were 177 healthy controls with no workplace exposure to carcinogenic or fibrogenic agents (mean age 39.2) and 1003 patients (mean age 67.5). The patients were 605 lung fibrosis patients (389 asbestosis, 161 silicosis, 55 lung interstitial fibrosis without relevant asbestos exposure), 364 lung cancer patients (49 asbestos-related, 315 without relevant asbestos exposure) and 34 diffuse malignant mesothelioma patients.
• Exposure: Occupational asbestos dust or silica dust, as recognised under the German list of occupational diseases (fiber types not specified). The genetic variants studied were IL-1β C-511T and C+3954T, IL-6 G-174C and IL-10 G-1082A.
• Main results:
  • Compared with healthy controls, the authors reported a higher risk for malignant mesothelioma patients for all investigated variants. None of these estimates was statistically significant.
  • IL-6 -174 C-allele carriers: odds ratio 1.338 (95% CI 0.71 to 2.53) for asbestosis. Odds ratio 1.226 (0.54 to 2.81) for silicosis.
  • IL-6 -174 C-allele carriers: odds ratio 1.918 (95% CI 0.68 to 5.45) for malignant mesothelioma. Odds ratio 2.112 (0.75 to 5.92) for asbestos-induced lung cancer. Odds ratio 1.00 (0.52 to 1.93) for lung cancer of other aetiology.
  • IL-10 -1082 A-allele carriers: odds ratio 2.064 (95% CI 0.78 to 5.49) for silicosis. Odds ratio 0.986 (0.48 to 2.03) for asbestosis.
  • IL-10 -1082 A-allele carriers: odds ratio 1.726 (95% CI 0.54 to 5.51) for malignant mesothelioma.
  • IL-1β -511 T-allele carriers: odds ratio 0.946 (95% CI 0.50 to 1.79) for asbestosis. Odds ratio 1.28 (0.49 to 3.33) for malignant mesothelioma.
  • IL-1β +3954 T-allele carriers: odds ratio 1.27 (95% CI 0.47 to 3.47) for asbestos-induced lung cancer. None of the reported results reached statistical significance.
• The authors' conclusion: The authors concluded that the study did not reveal sufficient evidence for an association of the investigated interleukin variants with asbestos- or silica-induced diseases. They called for further studies of combination effects and gene-environment interactions.
• Limitations the authors state:
  • The authors noted that, because carcinogenesis and fibrogenesis are complex, the effect of a single variant may be too small to reach statistical significance.

Topics

Medical terms in this study, explained in our Lexicon: Pneumoconiosis, Inflammation, Fibrosis, Interleukins, Carcinogenesis, Lung Cancer, Malignant Mesothelioma, Silicosis.

Related studies

• Tumour necrosis factor-alpha gene polymorphisms in asbestos-induced diseases — S. Helmig, N. Aliahmadi, et al. (2010)
• Association of transforming growth factor beta1 gene polymorphisms and asbestos-induced fibrosis and tumors — S. Helmig, A. Belwe, et al. (2009)
• Heme oxygenase-1 promoter polymorphism is associated with risk of malignant mesothelioma — A. Murakami, Y. Fujimori, et al. (2012)
• The role of polymorphisms in glutathione-related genes in asbestos-related diseases — A. Franko, K. Goricar, et al. (2021)
• Polymorphisms in oxidative stress-related genes are not associated with prostate cancer risk in heavy smokers — J.Y. Choi, M.L. Neuhouser, et al. (2007)
• Polymorphisms in DNA repair genes as risk factors for asbestos-related malignant mesothelioma in a general population study — I. Dianzani, L. Gibello, et al. (2006)

Browse more research in International Journal of Molecular Medicine, or return to medical research.