Individual predictors of increased serum mesothelin in asbestos-exposed workers

Our plain-English summary of Individual predictors of increased serum mesothelin in asbestos-exposed workers, by R. Filiberti, P. Marroni, M. Mencoboni, et al (Medical Oncology, 2013).

The study

• Authors: R. Filiberti, P. Marroni, M. Mencoboni, V. Mortara, P. Caruso, A. Cioè, L. Michelazzi, D.F. Merlo, A. Bruzzone, B. Bobbio, L. Del Corso, R. Galli, P. Taveggia, G. Dini, F. Spigno
• Journal: Medical Oncology
• Published: 2013;30(1):422
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The soluble mesothelin-related peptide (SMRP), a candidate marker for screening of subjects with asbestos exposure, is influenced by some individual and clinical factors. The aim of this study was to quantify the role of age, smoking, weight, presence of diseases and exposure to asbestos on serum SMRP levels in a large series of subjects exposed to asbestos, possible candidates for mesothelioma screening. One thousand seven hundred and four participants underwent clinical examination and were interviewed on medical anamnesis, occupation, smoking and weight. SMRP was measured by an ELISA assay. Overall, median SMRP was 0.4 (IQR 25-75: 0.3-0.7) nmol/l. It was higher in current smokers and in subjects with a cumulative asbestos exposure >50 ff/cc/years than in all the other subjects (p < 0.001 and p = 0.002, respectively). SMRP was positively correlated with age (ρ = 0.11, p < 0.001) and, inversely, with BMI (ρ = -0.15, p < 0.001). SMRP was lower in healthy subjects (n = 1,217: median 0.4 nmol/l) than in subjects with malignant tumors (n = 118: 0.5 nmol/l; p = 0.01), asbestos-related pleural lesions (plaques or thickenings, n = 152: 0.6 nmol/l; p < 0.001) and other benign diseases (n = 182: 0.5 nmol/l; p = 0.04). Multivariate analysis revealed significant predictors of increased SMRP: age >57 years, current smoking, a positive anamnesis for cancer and for asbestos-related pleural lesions, and BMI < 25. Some clinical and demographic variables are associated with serum SMRP levels. The degree of these associations is low, nevertheless they should be accounted for in the interpretation of SMPR as a candidate marker predictive of mesothelioma. The potential predictive value of serum SMRP in screening/surveillance programs must be validated in prospective studies.

In plain English

This study measured serum soluble mesothelin-related peptide (SMRP), a candidate mesothelioma screening marker, in 1,704 asbestos-exposed workers. They were retired or active dock, shipyard and steel workers in Genoa, Italy, examined in 2008 and 2009. Workplace fiber measurements were unavailable, so cumulative exposure was estimated from published data on similar workplaces and periods. Overall median SMRP was 0.4 nmol/l. After adjustment, the top third of SMRP values (above 0.6 nmol/l) was more likely in people over 57. It was also more likely in current smokers versus never or former smokers (odds ratio 2.16, 95% CI 1.50 to 3.11). Versus healthy people, it was more likely with cancer history (1.72, 1.06 to 2.78) or pleural plaques or thickening (3.26, 2.02 to 5.28). It was less likely with body mass index 25 or more versus below 25 (0.58, 0.44 to 0.76). Workers above 50 estimated fibers/cc/years had higher SMRP, but their odds ratio (1.64, 0.96 to 2.78) had a confidence interval including 1. The authors noted the differences were small, with medians below a possible normal cutoff. They concluded these factors should be considered in surveillance and that SMRP's predictive value needs prospective testing.

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 study: a single serum SMRP measurement in workers with past asbestos exposure, analyzed against personal and clinical factors
• Who was studied: 1,704 of 3,080 eligible workers (55.3%). They were retired or active workers from the dock/ship/yard of Genoa or from iron and steel industries in Genoa County, Italy. They were identified from the INAIL database, had to be alive on January 1, 2008, and had been occupationally exposed to asbestos for at least 1 year. They were examined between March 2008 and August 2009.
• Exposure: Occupational asbestos exposure in shipyard work, longshore work (loading and unloading goods including asbestos) and large steel mills. Average exposure duration was 29 years (range 1 to 49). Cumulative exposure in ff/cc/years was estimated with the German HVBG method. Historical fiber measurements from these workers' own workplaces were not available, so the estimates used literature databases of data from analogous working conditions, similar occupational settings and comparable historic periods. Fiber types are not specified.
• Main results:
  • Overall median SMRP in all participants was 0.4 nmol/l (interquartile range 0.3 to 0.7).
  • Age: participants aged 57 or younger had median SMRP 0.4 nmol/l and those older than 57 had 0.5 nmol/l (p less than 0.001). In the adjusted analysis, the odds ratio for the highest SMRP third in those over 57, compared with those 57 or younger, was 1.80 (95% CI 1.35 to 2.41).
  • Current smoking, compared with never or ex smoking, was associated with being in the highest SMRP third: OR 2.16 (95% CI 1.50 to 3.11). No difference was seen between ex-smokers and never smokers (p = 0.1).
  • People with body mass index of 25 or more had lower SMRP than those under 25: OR for the highest SMRP third 0.58 (95% CI 0.44 to 0.76).
  • Asbestos: workers with estimated cumulative exposure above 50 ff/cc/years (99 subjects) had median SMRP 0.6 nmol/l, against 0.4 nmol/l in all others (p = 0.002). In the adjusted analysis their OR for the highest SMRP third was 1.64 (95% CI 0.96 to 2.78), with p for trend 0.009.
  • Median SMRP was 0.4 nmol/l in 1,217 healthy subjects, 0.5 nmol/l in 118 with a cancer history (p = 0.01), 0.6 nmol/l in 152 with asbestos-related pleural lesions (plaques or thickening; p less than 0.001), and 0.5 nmol/l in 182 with other benign diseases (p = 0.04).
  • In the adjusted analysis, compared with healthy subjects, asbestos-related pleural lesions had an OR of 3.26 (95% CI 2.02 to 5.28) for the highest SMRP third. A history of cancer at any time had an OR of 1.72 (95% CI 1.06 to 2.78).
  • In the 24 subjects with asbestosis, median SMRP was 0.4 nmol/l.
  • Differences in SMRP between groups were small, and median values in every group stayed below a possible cutoff for normality.
• The authors' conclusion: The authors concluded that SMRP is associated with clinical and demographic variables, although the differences were contained. They said these variables should be taken into account in surveillance programs using SMRP as a candidate marker predictive of mesothelioma, and that its predictive value must be validated in prospective studies.
• Limitations the authors state:
  • No historical airborne fiber measurements existed for these workplaces. Exposure was estimated from literature databases of analogous settings.
  • The authors had no data on kidney function (GFR, serum creatinine), which other studies link to SMRP levels.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelin, Soluble Mesothelin-Related Peptides (SMRP), Asbestos Exposure, Mesothelioma, Multivariate Analysis.

Related studies

• Is soluble mesothelin-related protein an upfront predictive marker of pleural mesothelioma? A prospective study on Italian workers exposed to asbestos — R. Filiberti, P. Marroni, et al. (2014)
• Mesothelin promoter variants are associated with increased soluble mesothelin-related peptide levels in asbestos-exposed individuals — C. De Santi, P. Pucci, et al. (2017)
• Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma — A. Cristaudo, A. Bonotti, et al. (2011)
• Changes of mesothelin and osteopontin levels over time in formerly asbestos-exposed power industry workers — M.K. Felten, K. Khatab, et al. (2014)
• Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals: a prospective longitudinal cohort study — K. Hollevoet, J. Van Cleemput, et al. (2011)
• Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best? — J. Creaney, D. Yeoman, et al. (2011)

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