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Mesothelin Gene Variants Affect Soluble Mesothelin-Related Protein Levels in the Plasma of Asbestos-Exposed Males and Mesothelioma Patients from Germany

Authors :
Hans-Peter Rihs
Swaantje Casjens
Irina Raiko
Jens Kollmeier
Martin Lehnert
Kerstin Nöfer
Kerstin May-Taube
Nina Kaiser
Dirk Taeger
Thomas Behrens
Thomas Brüning
Georg Johnen
Source :
Biology, Vol 11, Iss 12, p 1826 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

Malignant mesothelioma (MM) is a severe disease mostly caused by asbestos exposure. Today, one of the best available biomarkers is the soluble mesothelin-related protein (SMRP), also known as mesothelin. Recent studies have shown that mesothelin levels are influenced by individual genetic variability. This study aimed to investigate the influence of three mesothelin (MSLN) gene variants (SNPs) in the 5′-untranslated promoter region (5′-UTR), MSLN rs2235503 C > A, rs3764246 A > G, rs3764247 A > C, and one (rs1057147 G > A) in the 3′-untranslated region (3′-UTR) of the MSLN gene on plasma concentrations of mesothelin in 410 asbestos-exposed males without cancer and 43 males with prediagnostic MM (i.e., with MM diagnosed later on) from the prospective MoMar study, as well as 59 males with manifest MM from Germany. The mesothelin concentration differed significantly between the different groups (p < 0.0001), but not between the prediagnostic and manifest MM groups (p = 0.502). Five to eight mutations of the four SNP variants studied were associated with increased mesothelin concentrations (p = 0.001). The highest mesothelin concentrations were observed for homozygous variants of the three promotor SNPs in the 5′-UTR (p < 0.001), and the highest odds ratio for an elevated mesothelin concentration was observed for MSLN rs2235503 C > A. The four studied SNPs had a clear influence on the mesothelin concentration in plasma. Hence, the analysis of these SNPs may help to elucidate the diagnostic background of patients displaying increased mesothelin levels and might help to reduce false-positive results when using mesothelin for MM screening in high-risk groups.

Details

Language :
English
ISSN :
20797737
Volume :
11
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.21386d5f05ff4bd3ad52cb5e45c477fe
Document Type :
article
Full Text :
https://doi.org/10.3390/biology11121826