Haptoglobin phenotype: A germline risk factor for malignant pleural mesothelioma? A case-control study. in Clinica chimica acta; international journal of clinical chemistry / Clin Chim Acta. 2025 Jun 1;573:120309. doi: 10.1016/j.cca.2025.120309. Epub 2025 Apr 14.

2025

Tipo pubblicazione

Journal Article;

Autori/Collaboratori (5)Vedi tutti...

Lamote K
Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
Delanghe S
Department of Nephrology, Ghent University Hospital, Ghent, Belgium.
Speeckaert MM
Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Department of Nephrology, Ghent University Hospital, Ghent, Belgium; Research Foundation-Flanders (FWO), Brussels, Belgium.

et alii...

Abstract

PURPOSE: The pathogenesis of malignant pleural mesothelioma (MPM) is linked to asbestos-induced chronic inflammation, oxidant formation, hemolysis and subsequent hemoglobin (Hb) release, potentiating oxidative injury. Haptoglobin (Hp) serves as a major antioxidant by binding free Hb in order to prevent its harmful effects. Dependent on the Hp-phenotype, this complexing can be divergent, leading to additional formation of reactive oxygen species (ROS) above those directly induced by asbestos or released by inflammatory cells. In order to determine the Hp-phenotype as a risk factor in MPM, this case-control study compared the Hp-phenotype distribution in MPM patients with asymptomatic persons with former occupational asbestos exposure (AEx) and controls from a European population. MATERIALS AND METHODS: Hp-phenotyping was done on serum samples of 118 MPM patients and 96 AEx subjects by starch gel electrophoresis. The frequencies of Hp phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2) and alleles (Hp(1), Hp(2)) were compared with those from 918 healthy control subjects. RESULTS: The Hp 1-1 phenotype was overrepresented in MPM patients compared to AEx persons (P = 0.001) and healthy controls (P = 0.005). The relative risk for developing MPM when having the Hp 1-1 phenotype was 3.05 (1.47-6.34) for AEx subjects and 1.74 (1.19-2.54) for healthy controls compared to other phenotypes. CONCLUSION: Our results indicate an important role of the Hp-phenotype in MPM pathogenesis suggesting that Hp 1-1 phenotypic persons are more prone for MPM development. Apart from the asbestos-induced radical formation, this finding confirms the role of oxidative stress in cancer development.

PMID : 40239912

DOI : 10.1016/j.cca.2025.120309

Keywords

Risk Factors; Mesothelioma, Malignant/diagnosis; Humans; Male; Female; Middle Aged; Aged; Haptoglobins/analysis; Hemoglobins/analysis; Pleural Neoplasms/diagnosis; Asbestos/toxicity; Case-Control Studies;