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Haptoglobin phenotype: A germline risk factor for malignant pleural mesothelioma? A case-control study
Kevin Lamote1, Sigurd Delanghe2, Marijn M Speeckaert3
1Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
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 (Hp1, Hp2) 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.
Insights
The haptoglobin 1-1 (Hp 1-1) phenotype increases the risk of developing malignant pleural mesothelioma (MPM) after asbestos exposure. This finding highlights the role of oxidative stress in MPM pathogenesis.
Area of Science:
- Environmental Health
- Oncology
- Genetics
Background:
- Malignant pleural mesothelioma (MPM) pathogenesis involves asbestos-induced inflammation, oxidant formation, and hemoglobin release, leading to oxidative injury.
- Haptoglobin (Hp) is a key antioxidant that binds free hemoglobin (Hb), but Hp-phenotype influences reactive oxygen species (ROS) generation.
- Divergent Hp-phenotype complexing can exacerbate ROS formation beyond asbestos or inflammatory cell-induced levels.
Purpose of the Study:
- To investigate the haptoglobin (Hp) phenotype as a potential risk factor in malignant pleural mesothelioma (MPM).
- To compare Hp-phenotype distribution in MPM patients, asbestos-exposed individuals (AEx), and healthy controls from a European population.
Main Methods:
- Serum samples from 118 MPM patients and 96 AEx subjects were analyzed using starch gel electrophoresis for Hp-phenotyping.
- Frequencies of Hp phenotypes (Hp 1-1, Hp 2-1, Hp 2-2) and alleles (Hp¹, Hp²) were compared between cases, AEx, and 918 healthy controls.
Main Results:
- The Hp 1-1 phenotype was significantly overrepresented in MPM patients compared to both AEx individuals (P = 0.001) and healthy controls (P = 0.005).
- Individuals with the Hp 1-1 phenotype exhibited a 3.05-fold increased relative risk of developing MPM among AEx subjects and a 1.74-fold increased risk among healthy controls compared to other phenotypes.
Conclusions:
- The study indicates a significant role for the Hp-phenotype in MPM pathogenesis.
- Individuals with the Hp 1-1 phenotype appear more susceptible to developing MPM.
- This finding reinforces the contribution of oxidative stress to cancer development, beyond asbestos-induced radical formation.
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