<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec><h3>Background</h3>
<p>Asbestos exposure is associated with different asbestos-related diseases, including malignant mesothelioma (MM). MM diagnosis is confirmed with immunohistochemical analysis of several markers, including calretinin. Increased circulating calretinin was also observed in MM. The aim of the study was to determine if <italic>CALB2</italic> polymorphisms or polymorphisms in genes that can regulate calretinin expression are associated with serum calretinin levels or MM susceptibility.</p>
</sec>
<sec><h3>Subjects and methods</h3>
<p>The study included 288 MM patients and 616 occupationally asbestos-exposed subjects without MM (153 with asbestosis, 380 with pleural plaques and 83 without asbestos-related disease). Subjects were genotyped for seven polymorphisms in <italic>CALB2</italic>, <italic>E2F2</italic>, <italic>MIR335</italic>, <italic>NRF1</italic> and <italic>SEPTIN7</italic> genes using competitive allele-specific polymerase chain reaction (PCR). Serum calretinin was determined with ELISA in 545 subjects. Nonparametric tests, logistic regression and receiver operating characteristic (ROC) curve analysis were used for statistical analysis.</p>
</sec>
<sec><h3>Results</h3>
<p>Carriers of at least one polymorphic <italic>CALB2</italic> rs889704 allele had lower calretinin levels (P = 0.036). Carriers of two polymorphic <italic>MIR335</italic> rs3807348 alleles had higher calretinin (P = 0.027), while carriers of at least one polymorphic <italic>NRF1</italic> rs13241028 allele had lower calretinin levels (P = 0.034) in subjects without MM. Carriers of two polymorphic <italic>E2F2</italic> rs2075995 alleles were less likely to develop MM (odds ratio [OR] = 0.64, 95% confidence interval [CI] = 0.43-0.96, P = 0.032), but the association was no longer significant after adjustment for age (P = 0.093). Optimal serum calretinin cut-off values differentiating MM patients from other subjects differed according to <italic>CALB2</italic>, <italic>NRF1</italic>, <italic>E2F2</italic>, and <italic>MIR335</italic> genotypes.</p>
</sec>
<sec><h3>Conclusions</h3>
<p>The results of presented study suggest that genetic variability could influence serum calretinin levels. These findings could contribute to a better understanding of calretinin regulation and potentially to earlier MM diagnosis.</p>
</sec>
</abstract>

Background
Asbestos exposure is associated with different asbestos-related diseases, including malignant mesothelioma (MM). MM diagnosis is confirmed with immunohistochemical analysis of several markers, including calretinin. Increased circulating calretinin was also observed in MM. The aim of the study was to determine if CALB2 polymorphisms or polymorphisms in genes that can regulate calretinin expression are associated with serum calretinin levels or MM susceptibility.

Subjects and methods
The study included 288 MM patients and 616 occupationally asbestos-exposed subjects without MM (153 with asbestosis, 380 with pleural plaques and 83 without asbestos-related disease). Subjects were genotyped for seven polymorphisms in CALB2, E2F2, MIR335, NRF1 and SEPTIN7 genes using competitive allele-specific polymerase chain reaction (PCR). Serum calretinin was determined with ELISA in 545 subjects. Nonparametric tests, logistic regression and receiver operating characteristic (ROC) curve analysis were used for statistical analysis.

Results
Carriers of at least one polymorphic CALB2 rs889704 allele had lower calretinin levels (P = 0.036). Carriers of two polymorphic MIR335 rs3807348 alleles had higher calretinin (P = 0.027), while carriers of at least one polymorphic NRF1 rs13241028 allele had lower calretinin levels (P = 0.034) in subjects without MM. Carriers of two polymorphic E2F2 rs2075995 alleles were less likely to develop MM (odds ratio [OR] = 0.64, 95% confidence interval [CI] = 0.43-0.96, P = 0.032), but the association was no longer significant after adjustment for age (P = 0.093). Optimal serum calretinin cut-off values differentiating MM patients from other subjects differed according to CALB2, NRF1, E2F2, and MIR335 genotypes.

Conclusions
The results of presented study suggest that genetic variability could influence serum calretinin levels. These findings could contribute to a better understanding of calretinin regulation and potentially to earlier MM diagnosis.

The association of genetic factors with serum calretinin levels in asbestos-related diseases

Clinical Institute of Occupational Medicine

Faculty of Medicine, Institute of Biochemistry and Molecular Genetics

Radiology and Oncology

This work is licensed under the Creative Commons Attribution 4.0 International License.

Background
Asbestos exposure is associated with different asbestos-related diseases, including malignant mesothelioma (MM). MM diagnosis is confirmed with...

The association of genetic factors with serum calretinin levels in asbestos-related diseases

Article Category: Research Article

Published Online: Nov 30, 2023

Page range: 473 - 486

Received: Oct 19, 2023

Accepted: Oct 31, 2023

DOI: https://doi.org/10.2478/raon-2023-0061

Keywords
malignant mesothelioma, calretinin, CALB2, asbestos-related disease, polymorphism

© 2023 Cita Zupanc et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

The association of genetic factors with serum calretinin levels in asbestos-related diseases

Article Category: Research Article

Published Online: Nov 30, 2023

Page range: 473 - 486

Received: Oct 19, 2023

Accepted: Oct 31, 2023

DOI: https://doi.org/10.2478/raon-2023-0061

Keywordsmalignant mesothelioma, calretinin, CALB2, asbestos-related disease, polymorphism

© 2023 Cita Zupanc et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Keywords
malignant mesothelioma, calretinin, CALB2, asbestos-related disease, polymorphism