Tumour necrosis factor-alpha gene polymorphisms in asbestos-induced diseases

Our plain-English summary of Tumour necrosis factor-alpha gene polymorphisms in asbestos-induced diseases, by S. Helmig, N. Aliahmadi, J. Schneider (Biomarkers, 2010).

The study

• Authors: S. Helmig, N. Aliahmadi, J. Schneider
• Journal: Biomarkers
• Published: 2010;15(5):400-9
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Tumour necrosis factor (TNF)-alpha influences the pathogenesis of lung fibrosis and carcinogenesis in normal cells. Polymorphisms of this gene have been suggested to be associated with susceptibility to lung diseases.

Methods: Association studies were performed in German subjects, using control subjects (n = 177), pulmonary fibrosis patients (n = 612) and bronchial carcinoma patients (n = 374).

Results: Compared with a healthy (control) group, a significant result could be obtained for the asbestosis (patient) group (crude odds ratio (OR(crude)) = 1.57; 95% confidence interval (CI) 1.05-2.36; p = 0.03), especially with severe lung asbestosis (OR(crude) = 4.15; 95% CI 1.06-16.16; p = 0.04). A significant association was revealed when comparing asbestosis patients (OR(crude) = 4.08; 95% CI 1.53-10.54; p = 0.004 and OR(adjusted) = 3.89; 95% CI 1.49-10.17; p = 0.006) with asbestos-induced lung cancer patients.

Conclusion: The results confirm the hypothesis that TNF-alpha polymorphisms are associated with asbestos-induced fibrotic or malignant lung diseases in Germans.

In plain English

This German case-control study tested whether two variants of the gene for tumour necrosis factor (TNF)-alpha, an inflammatory signalling protein, were linked to asbestos-related and other lung diseases. The authors analysed blood DNA from 1196 people: 177 healthy controls with no workplace exposure to carcinogenic agents, 612 lung fibrosis patients (395 with asbestosis), 374 lung cancer patients (48 asbestos-related) and 33 diffuse malignant mesothelioma patients. Compared with controls, people carrying at least one A allele at position -308 had a crude odds ratio for asbestosis of 1.57 (95% CI 1.05 to 2.36). After adjusting for age, gender and smoking it was 1.62 (0.82 to 3.21), which was not statistically significant. In nine patients with severe lung asbestosis the crude odds ratio was 4.15 (1.06 to 16.16). When asbestosis patients were compared with asbestos-related lung cancer patients, the adjusted odds ratio was 3.89 (1.49 to 10.17). No significant results were found for mesothelioma or for the -238 variant. Controls were younger (mean 39.1 years) than cases (67.4). The authors concluded that the -308 A allele was significantly associated with a higher risk of fibrotic lung diseases.

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 frequencies of two TNF-alpha gene promoter variants (-238 and -308) between healthy controls and disease groups, using crude and adjusted odds ratios from logistic regression
• Who was studied: 1196 German subjects examined at Giessen, Germany: 177 healthy controls; 612 lung fibrosis patients (395 asbestosis, 162 silicosis, 55 lung interstitial fibrosis without relevant asbestos or silica exposure); 374 lung cancer patients (48 asbestos-related, 326 without relevant asbestos exposure); and 33 diffuse malignant mesothelioma patients. Study dates are not given.
• Exposure: Occupational asbestos dust exposure. No fiber types are named. Asbestosis was defined as German occupational disease No. 4103 BKV. Asbestos-related lung cancer (No. 4104 BKV) required asbestosis, pleural plaques, or cumulative asbestos exposure of at least 25 fibres/ml times years. Silica-exposed and non-exposed patients served as comparison groups.
• Main results:
  • TNF-alpha -308 A allele carriers, asbestosis group (4103 BKV) versus controls: crude OR 1.57 (95% CI 1.05 to 2.36; p = 0.03). Adjusted for pack-years, age and gender: OR 1.62 (0.82 to 3.21; p = 0.17).
  • Severe lung asbestosis subgroup (ILO 3/2, 3/3 and 3/+), -308 A allele versus controls: crude OR 4.15 (95% CI 1.06 to 16.16; p = 0.04). The adjusted OR in the table was 5.55 (0.91 to 33.72; p = 0.06).
  • Hyaline pleural plaques group, -308 A allele versus controls: crude OR 2.21 (CI printed as 1.11 to 4.1 in the text and 1.11 to 4.41 in the table; p = 0.02). Adjusted OR 2.90 (95% CI 1.08 to 7.78; p = 0.03).
  • Asbestosis patients compared with asbestos-induced lung cancer patients, -308 A allele: crude OR 4.08 (95% CI 1.53 to 10.54; p = 0.004) and adjusted OR 3.89 (95% CI 1.49 to 10.17; p = 0.006).
  • Asbestos-induced bronchial carcinoma versus controls, -308 A allele: crude OR 0.39 (95% CI 0.14 to 1.04). No association was found after adjustment.
  • Diffuse malignant mesothelioma versus controls, -308 A allele: crude OR 0.74 (95% CI 0.29 to 1.91; p = 0.53), not significant.
  • For the TNF-alpha -238 variant, no result was statistically significant, either against controls or when fibrosis patients were compared with lung cancer patients.
• The authors' conclusion: The authors concluded that the A allele at position -308 of TNF-alpha was significantly associated with a higher risk for fibrotic lung diseases. They also concluded it was associated with higher risk for fibrosis and lower risk for lung cancer when those two groups were compared. In the abstract they stated that the results confirm the hypothesis that TNF-alpha polymorphisms are associated with asbestos-induced fibrotic or malignant lung diseases in Germans.
• Limitations the authors state:
  • The authors suggested that the lack of a significant -238 association in silicosis may be because they did not separate silicosis patients by severity.
  • The authors suggested that the low frequency of the -238 A allele may explain why they did not detect significant results for that variant.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Necrosis, Fibrosis, Carcinogenesis, Pulmonary Fibrosis, Carcinoma, Odds Ratio, confidence interval, Lung Cancer.

Related studies

• Association of transforming growth factor beta1 gene polymorphisms and asbestos-induced fibrosis and tumors — S. Helmig, A. Belwe, et al. (2009)
• Reduced tumor necrosis factor-alpha and transforming growth factor-beta1 expression in the lungs of inbred mice that fail to develop fibroproliferative lesions consequent to asbestos exposure — D.M. Brass, G.W. Hoyle, et al. (1999)
• Asbestos fibres and man made mineral fibres: induction and release of tumour necrosis factor-alpha from rat alveolar macrophages — A.G. Ljungman, M. Lindahl, et al. (1994)
• Is a single nucleotide polymorphism a risk factor for lung cancer in the matrix metalloproteinase-2 promoter? — B. Ayşegül, G.H. Veysi, et al. (2011)
• Iron and reactive oxygen species in the asbestos-induced tumor necrosis factor-alpha response from alveolar macrophages — P.P. Simeonova, M.I. Luster (1995)
• Polymorphisms of glutathione-S-transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma — S. Landi, F. Gemignani, et al. (2007)

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