Serum oncoproteins and growth factors in asbestosis and silicosis patients

Our plain-English summary of Serum oncoproteins and growth factors in asbestosis and silicosis patients, by P.W. Brandt-Rauf, S. Smith, K. Hemminki, et al (International Journal of Cancer, 1992).

The study

• Authors: P.W. Brandt-Rauf, S. Smith, K. Hemminki, H. Koskinen, H. Vainio, H. Niman, J. Ford
• Journal: International Journal of Cancer
• Published: 1992;50(6):881-5
• Cited by: 56 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Levels of 9 different oncoproteins and growth factors were assayed by immunoblotting with monoclonal antibodies in 91 serum samples collected between March 1983 and August 1987 from 46 pneumoconiosis patients (36 asbestosis, 10 silicosis) at high risk for the development of cancer. Follow-up of these patients through June 1991 showed that 18 had developed cancer (11 lung, 2 pleural mesothelioma, 2 transitional-cell carcinomas of the urinary bladder, 1 osteosarcoma, 1 non-Hodgkin's lymphoma, 1 adenocarcinoma of the gallbladder). Increased serum levels of ras oncogene-related protein (p21) were found in 7 of the 18 patients who developed cancer (5 lung, 2 pleural mesothelioma) versus 2 of the 28 patients without cancer, a statistically significant difference (p = 0.012). In addition, 6 of the 7 p21-positive cancer cases had positive serum samples prior to clinical diagnosis of disease (average = 16.3 months, range = 3-26 months prior to diagnosis), suggesting that elevated serum p21 levels may be a useful marker for earlier detection in a significant percentage of respiratory malignancies. Finally, elevated serum levels of PDGF-related protein were detected significantly more frequently in advanced pneumoconiosis cases (ILO radiographic classification of 2/1 or greater) than in less advanced cases (80% vs. 41.9%; p = 0.016), and there was a tendency for these PDGF-positive patients to have progression of their disease (68.2% vs. 41.7%; p = 0.065), suggesting that elevated serum PDGF levels may be a marker for the development of severe and progressive pneumoconioses.

In plain English

This case-referent study drew on patients with compensated asbestosis or silicosis followed at the Institute of Occupational Health in Finland. The authors tested 91 stored serum samples, taken between March 1983 and August 1987, from 46 patients (36 with asbestosis, 10 with silicosis) for raised levels of 9 cancer-related proteins and growth factors. By June 1991, 18 of the 46 had developed cancer. A raised level of the ras protein p21 was found in 7 of 18 patients with cancer (38.9%) versus 2 of 28 without cancer (7.1%), p = 0.012. All 7 were asbestos-exposed and had lung cancer or mesothelioma, and 6 had a positive sample before diagnosis. The growth factor PDGF was raised in 12 of 15 patients with advanced pneumoconiosis (80%) versus 13 of 31 others (41.9%). The authors suggested that p21 may appear in serum up to about 1-2 years before diagnosis in some lung cancers and mesotheliomas. They noted that the p21 difference lost statistical significance after correcting for testing 9 proteins.

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-referent (case-control) study nested in a clinical cohort, using stored (banked) serum samples tested by immunoblotting with monoclonal antibodies
• Who was studied: 46 patients drawn from a cohort of 115 asbestosis and 144 silicosis patients followed at the Institute of Occupational Health in Finland from 1978 until August 1987. The final subset was 15 asbestosis patients with cancer and 21 without, plus 3 silicosis patients with cancer and 7 without. Non-cancer referents were matched on age and smoking. All were Caucasian, 93% were male, and the average age was 67. Cancer follow-up ran to June 1991.
• Exposure: Occupational exposure to asbestos or silica dust, averaging 21 years (range 4-41). Jobs listed for the asbestosis patients include asbestos mining, pipe insulator, asbestos cement, asbestos sprayer and carpenter. Jobs listed for the silicosis patients include stone worker, miner, foundry worker and stone crusher. Fiber types are not specified.
• Main results:
  • Raised serum ras protein (p21) was found in 7 of 18 patients who developed cancer (38.9%) versus 2 of 28 patients without cancer (7.1%), p = 0.012.
  • All 7 p21-positive cancer patients were asbestos-exposed and had lung cancer or mesothelioma.
  • In 6 of the 7 p21-positive cancer patients, a p21-positive sample had been taken before clinical diagnosis.
  • For the 2 mesothelioma patients, serum was p21-positive 11 and 26 months before clinical diagnosis. For 4 lung cancer patients, it was positive an average of 15.2 months (range 3-24 months) before diagnosis.
  • Being positive for at least one of the proteins did not differ between patients with cancer (13 of 18, 72.2%) and without cancer (20 of 28, 71.4%).
  • Raised oncoprotein levels were found only in the asbestosis patients, while raised PDGF was found in both groups.
  • Raised PDGF was found in 12 of 15 patients with advanced pneumoconiosis (ILO 2/1 or greater, 80%) versus 13 of 31 other patients (41.9%), p = 0.016.
  • PDGF was raised in 15 of 22 patients whose pneumoconiosis progressed (68.2%) versus 10 of 24 without progression (41.7%), p = 0.065. The authors say this trend did not quite reach statistical significance.
  • Raised PDGF was found in all 10 silicosis patients, compared with 15 of 36 asbestosis patients (41.7%).
• The authors' conclusion: The authors concluded that in some cases of lung cancer and mesothelioma, increased p21 occurs and can be detected in serum up to about 1-2 years before clinical diagnosis. They also suggested that raised serum PDGF may correspond with advanced and progressive pneumoconiosis.
• Limitations the authors state:
  • The higher rate of p21 in cancer cases may have occurred by chance. After a Bonferroni correction for testing 9 proteins, the p21 difference was no longer statistically significant, and the authors say further study is needed.
  • For most p21-positive cancer patients there were no earlier negative samples, so the estimates of how long before diagnosis p21 became raised are minimums.
  • Some p21-negative lung cancer patients had no sample taken near the time of diagnosis.
  • Numbers were too small to draw conclusions about p21 by lung cancer subtype.

Topics

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

Medical terms in this study, explained in our Lexicon: Silicosis, Monoclonal, Pneumoconiosis, Pleural Mesothelioma, Carcinoma, Adenocarcinoma, Platelet-Derived Growth Factor (PDGF).

Related studies

• Serum growth factors in asbestosis patients — Y. Li, A. Karjalainen, et al. (2009)
• The molecular epidemiology of oncoproteins. Serum p53 protein in patients with asbestosis — K. Hemminki, R. Partanen, et al. (1996)
• Serum concentrations of Krebs von den Lungen-6, surfactant protein D, and matrix metalloproteinase-2 as diagnostic biomarkers in patients with asbestosis and silicosis: a case-control study — C. Xue, N. Wu, et al. (2017)
• The pathobiology of asbestos-induced lung disease: a proposed role for macrophage-derived growth factors — J.A. Lasky, J.C. Bonner, et al. (1991)
• Mechanisms in the pathogenesis of asbestosis and silicosis — B.T. Mossman, A. Churg (1998)
• Current concepts about the pathogenesis of silicosis and asbestosis — R.D. deShazo (1982)

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