Increased serum concentrations of growth factor receptors and Neu in workers previously exposed to asbestos

Our plain-English summary of Increased serum concentrations of growth factor receptors and Neu in workers previously exposed to asbestos, by N. Lahat, P. Froom, E. Kristal-Boneh, et al (Occupational and Environmental Medicine, 1999).

The study

• Authors: N. Lahat, P. Froom, E. Kristal-Boneh, C. Cohen, Y. Lerman, J. Ribak
• Journal: Occupational and Environmental Medicine
• Published: 1999;56(2):114-7
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Epidermal growth factor receptor (EGFR) and oncogene Neu belong to a family of growth factor receptors which may play a part in carcinogenesis. Although increased serum concentrations of Neu and EGFR have been shown in several patients with asbestosis who later developed cancer, serum concentrations have not been studied in workers exposed in the past to asbestos but without asbestos related diseases.

Methods: Serum concentrations of secreted growth factor receptors were studied in 300 workers exposed in the past to asbestos and the results were compared with those of 70 controls.

Results: In the controls 4.3% (3/70) had EGFR values > 912 units/ml, compared with 39% (117/299) of the exposed group (p < 0.001). The difference in high values was even more pronounced for Neu with 4.3% of controls having Neu values > 2580 fmol/ml compared with 72% (216/299) of the exposed workers (p < 0.001). Pleural plaques predicted lower serum concentrations of EGFR but not lower Neu concentrations, and this finding remained significant after adjustment for age, exposure time, smoking, and time from initial exposure.

Conclusions: Enhanced secretion of EGFR and Neu was found in a large cohort of retired asbestos workers with a wide range of exposure and latency periods. They did not have asbestosis or cancer and their EGFR values were higher in those without plaques. Further studies are needed to confirm our results, to determine the source of the secreted growth factor receptors, and to study their possible value as risk factors in the development of cancer.

In plain English

This study, by researchers in Israel, measured two proteins in the blood: epidermal growth factor receptor (EGFR) and Neu. The authors describe them as growth factor receptors that may play a part in cancer development. They tested blood from 300 retired workers of a single asbestos cement factory, where the ratio of chrysotile to crocidolite fibres had been 10:1. From 1119 workers examined, all 80 with pleural plaques were included, plus 220 chosen at random. These workers were compared with 70 healthy controls who were relatives of outpatient clinic patients. High EGFR values (above 912 fmol/ml) were found in 3 of 70 controls (4.3%) and in 117 of 299 exposed workers (39.1%). High Neu values (above 2580 units/ml) were found in 4.3% of controls and in 216 of 299 workers (72%). Workers with pleural plaques were less likely to have high EGFR. Plaques were not linked to Neu. The authors said the workers did not have asbestosis or cancer. They noted selection bias, because only living volunteers were included. They said high levels would likely be a poor predictor of future cancer, and that further studies are needed.

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: Cross-sectional comparison of blood (serum) levels of EGFR and Neu, measured by ELISA, in retired asbestos workers versus controls
• Who was studied: 300 retired workers of a single asbestos cement factory, chosen from 1119 examined workers: all 80 with pleural plaques plus 220 chosen at random. Median age 60 (range 34 to 86). Examined a median of 32 years after first exposure. They were compared with 70 healthy controls, who were relatives of outpatient clinic patients with similar social conditions and age range. The factory's location is not named; the authors are based in Israel.
• Exposure: Work making asbestos cement products (pipes and sheets) from 1953. The ratio of chrysotile to crocidolite was 10:1 until crocidolite was eliminated in recent years. Concentrations were 4 to 40 fibres/ml in the 1960s and 1970s, and below 1 fibre/ml since 1977. Exposure lasted 1 to 40 years (median 4 years).
• Main results:
  • High EGFR (above 912 fmol/ml) was found in 3 of 70 controls (4.3%) and in 117 of 299 exposed workers (39.1%). High Neu (above 2580 units/ml) was found in 4.3% (3 of 70) of controls and in 72% (216 of 299) of exposed workers. p less than 0.001 in both cases.
  • Median serum EGFR was 800 fmol/ml (25th to 75th percentile 650 to 1225) in exposed workers and 409 (274 to 599) in controls, p less than 0.001.
  • Median serum Neu was 3600 units/ml (2500 to 5200) in exposed workers and 1533 (1163 to 1812) in controls, p less than 0.001.
  • Among exposed workers, those with pleural plaques were less likely to have high EGFR after controlling for the other variables (odds ratio 0.49, 95% CI 0.28 to 0.84, p equal to 0.010).
  • Pleural plaques were found equally often in workers with high and normal Neu values.
  • Latency and length of exposure were not associated with high EGFR values.
  • Current smoking was more common in workers with high Neu (57 of 216, 26.4%) than in those with normal Neu (13 of 83, 15.7%), p equal to 0.0498. This was not significant after correction for multiple comparisons.
  • In a model that included high EGFR, smoking became a significant predictor of high Neu (odds ratio 2.03, 95% CI 1.01 to 4.09).
  • Among exposed workers, a high Neu value predicted a high EGFR value (odds ratio 4.61, 95% CI 2.58 to 8.22).
• The authors' conclusion: The authors concluded that secretion of EGFR and Neu was raised in this cohort of retired asbestos workers. They stated these workers did not have asbestosis or cancer, and that EGFR values were higher in those without plaques. They said further studies are needed to confirm the results, to find the source of the receptors, and to study their possible value as risk factors for cancer.
• Limitations the authors state:
  • Considerable selection bias: workers who had died were excluded, and only workers who volunteered for the examination were included.
  • Because high values were so common in a relatively healthy cohort, the positive predictive value of high receptor levels for future cancer is likely to be low.
  • Some cross reactivity between the antibodies in the two assays could partly explain the correlation between EGFR and Neu levels.

Topics

Medical terms in this study, explained in our Lexicon: EGFR, Carcinogenesis, Pleural Plaques, Latency.

Related studies

• Increased epidermal growth factor-receptor protein in a human mesothelial cell line in response to long asbestos fibers — J.C. Pache, Y.M. Janssen, et al. (1998)
• Increased expression of epidermal growth factor receptor in rat pleural mesothelial cells correlates with carcinogenicity of mineral fibres — S.P. Faux, C.E. Houghton, et al. (2000)
• Role of iron in inactivation of epidermal growth factor receptor after asbestos treatment of human lung and pleural target cells — A. Baldys, A.E. Aust (2005)
• Epidermal growth factor receptor mutations in malignant pleural and peritoneal mesothelioma — Y. Enomoto, T. Kasai, et al. (2012)
• A comparison of epidermal growth factor receptor expression in malignant peritoneal and pleural mesothelioma — Y. Enomoto, T. Kasai, et al. (2012)
• Malignant pleural mesothelioma and epidermal growth factor receptor (EGF-R). Relationship of EGF-R with histology and survival using fixed paraffin embedded tissue and the F4, monoclonal antibody — H. Dazzi, P.S. Hasleton, et al. (1990)

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