Assessment of Confounding Factors Affecting the Tumor Markers SMRP, CA125, and CYFRA21-1 in Serum

Our plain-English summary of Assessment of Confounding Factors Affecting the Tumor Markers SMRP, CA125, and CYFRA21-1 in Serum, by D.G. Weber, G. Johnen, D. Taeger, et al (Biomarker Insights, 2010).

The study

• Authors: D.G. Weber, G. Johnen, D. Taeger, A. Weber, I.M. Gross, B. Pesch, T. Kraus, T. Brüning, M. Gube
• Journal: Biomarker Insights
• Published: 2010;5:1-8
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The purpose of this analysis was to evaluate if serum levels of potential tumor markers for the diagnosis of malignant mesothelioma and lung cancer are affected by confounding factors in a surveillance cohort of workers formerly exposed to asbestos. SMRP, CA125, and CYFRA21-1 concentrations were determined in about 1,700 serum samples from 627 workers formerly exposed to asbestos. The impact of factors that could modify the concentrations of the tumor markers was examined with linear mixed models. SMRP values increased with age 1.02-fold (95% CI 1.01-1.03) and serum creatinine concentration 1.32-fold (95% CI 1.20-1.45). Levels differed by study centers and were higher after 40 years of asbestos exposure. CA125 levels increased with longer storage of the samples. CYFRA21-1 values correlated with age 1.02-fold (95% CI 1.01-1.02), serum creatinine 1.21-fold (95% CI 1.14-1.30) and varied by study centers due to differences in sample handling. Tumor marker concentrations are influenced by subject-related factors, sample handling, and storage. These factors need to be taken into account in screening routine.

In plain English

This study measured SMRP, CA125 and CYFRA21-1, blood markers studied for detecting malignant mesothelioma and lung cancer. The authors tested about 1,700 frozen serum samples, collected yearly from 1993 to 1997, from 626 German former asbestos workers, excluding samples taken after a mesothelioma or lung cancer diagnosis. Gender, smoking, CRP, pleural or lung changes, and later mesothelioma had no significant influence on any marker. SMRP rose 1.02-fold per year of age (95% CI 1.01–1.03) and 1.32-fold per ng/ml of creatinine, a kidney indicator (95% CI 1.20–1.45). It was higher in the longest-exposed group (median 0.98 versus 0.70 nmol/l) and at two centers. CA125 was 1.23-fold higher (95% CI 1.18–1.29) after twelve years of storage than after nine. CYFRA21-1 rose 1.02-fold per year of age (95% CI 1.01–1.02) and 1.21-fold per ng/ml creatinine (95% CI 1.14–1.30), was 1.42-fold higher in people later diagnosed with lung cancer (95% CI 1.12–1.79), and varied by center. The authors concluded that age, creatinine, exposure duration, sample handling and storage time affected marker levels, and that accounting for them might reduce false positives.

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: Analysis of repeated stored serum samples from a surveillance cohort of formerly asbestos-exposed workers, using linear mixed models
• Who was studied: The study group was 627 German asbestos workers, with blood drawn yearly from 1993 to 1997; about 1,700 serum samples were available in 2005. One person with lung cancer diagnosed in 1993 was excluded, leaving 626 participants. Samples taken after a diagnosis of malignant mesothelioma or lung cancer were also excluded. Mortality follow-up ran until April 2007. Median age at baseline was 63 years (range 53–70), and 91.9% (575) were male.
• Exposure: Former occupational asbestos exposure (fiber type not stated). The median duration of exposure was 19 years, with a range of 1 to 52 years.
• Main results:
  • Across the study group, median SMRP was 0.72 nmol/l (IQR 0.50–1.03 nmol/l).
  • Gender, smoking status, CRP, pleural or lung alterations, and development of malignant mesothelioma had no significant influence on any of the three markers.
  • SMRP increased 1.02-fold per year of age (95% CI 1.01–1.03, p = 0.0014) and 1.32-fold per ng/ml serum creatinine (95% CI 1.20–1.45).
  • Median SMRP was elevated in participants in the longest asbestos-exposure category, 40 years (0.98 nmol/l), compared with other participants (0.70 nmol/l, p = 0.0002).
  • Two study centers had elevated SMRP levels. SMRP and CYFRA21-1 differed between some study centers, while CA125 did not.
  • CA125 was 1.23-fold higher (95% CI 1.18–1.29) after twelve years of storage than after nine years (median 8.90 KIU/l). SMRP and CYFRA21-1 were not affected by storage time.
  • CYFRA21-1 was 1.42-fold higher (95% CI 1.12–1.79, p = 0.0033) in participants later diagnosed with lung cancer; the samples analysed were taken before diagnosis.
  • CYFRA21-1 rose 1.02-fold per year of age (95% CI 1.01–1.02, p = 0.0005) and 1.21-fold per ng/ml creatinine (95% CI 1.14–1.30).
• The authors' conclusion: The authors concluded that age, serum creatinine, duration of asbestos exposure, sample handling procedures and storage time were significant confounders of serum marker levels. They added that taking these into account might reduce false-positive cases in screening programs.
• Limitations the authors state:
  • Few participants had the longest asbestos exposure, and the authors said further analyses are needed before SMRP could be used as a marker of asbestos exposure.
  • The study did not assess how well the markers detect malignant mesothelioma or lung cancer (sensitivity and specificity).
  • The authors suggested that the differences between study centers might be caused by different sample handling between blood drawing and freezing, but they did not confirm this.

Topics

Medical terms in this study, explained in our Lexicon: Confounding, Tumor Marker, Soluble Mesothelin-Related Peptides (SMRP), Malignant Mesothelioma, Lung Cancer, Asbestos Exposure.

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