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

Cita Zupanc

Cita Zupanc

  • Military Medical Unit-Slovenian ArmyLjubljana, Slovenia
  • University of Ljubljana, Faculty of MedicineLjubljana, Slovenia
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Zupanc, Cita
, 
Alenka Franko

Alenka Franko

  • University of Ljubljana, Faculty of MedicineLjubljana, Slovenia
  • University Medical Centre Ljubljana, Clinical Institute of Occupational MedicineLjubljana, Slovenia
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Franko, Alenka
, 
Danijela Strbac

Danijela Strbac

  • University of Ljubljana, Faculty of MedicineLjubljana, Slovenia
  • Institute of Oncology LjubljanaLjubljana, Slovenia
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Strbac, Danijela
, 
Viljem Kovac

Viljem Kovac

  • University of Ljubljana, Faculty of MedicineLjubljana, Slovenia
  • Institute of Oncology LjubljanaLjubljana, Slovenia
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Kovac, Viljem
, 
Vita Dolzan

Vita Dolzan

University of Ljubljana, Faculty of Medicine, Institute of Biochemistry and Molecular Genetics, Pharmacogenetics LaboratoryLjubljana, Slovenia
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Dolzan, Vita
 and 
Katja Goricar

Katja Goricar

University of Ljubljana, Faculty of Medicine, Institute of Biochemistry and Molecular Genetics, Pharmacogenetics LaboratoryLjubljana, Slovenia
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Goricar, Katja
  
Nov 30, 2023
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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
© 2023 Cita Zupanc et al., published by Sciendo
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 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.
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Medicine, Clinical Medicine, Internal Medicine, Haematology, Oncology, Radiology
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