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Altitude and paraganglioma.
Julie Sanceau1, Rebecca Westbrook1, Judith Favier1
1Inserm, équipe labellisée Ligue contre le cancer, centre de recherche des Cordeliers, université Paris-Cité, Sorbonne université, 75006 Paris, France.
Annales D'Endocrinologie
|May 8, 2025
Summary
High altitude and low oxygen (hypoxia) may drive paraganglioma (PGL) development. Genetic mutations and diseases causing hypoxia also increase PGL risk, highlighting hypoxia
Area of Science:
- Endocrinology
- Oncology
- Environmental Medicine
Background:
- Paragangliomas (PGLs) are rare sympathetic nervous system tumors.
- Altitude is associated with PGL development, linked to lower barometric pressure and hypoxia.
- Chronic hypoxia induces physiological changes like carotid body (CB) hyperplasia.
Purpose of the Study:
- To review the influence of altitude-mediated hypoxia on paraganglioma (PGL) development.
- To explore the role of hypoxia signaling in PGL tumorigenesis.
- To examine genetic and disease-related factors contributing to hypoxia-induced PGL.
Main Methods:
- Literature review of studies investigating altitude, hypoxia, and PGL.
- Analysis of physiological responses to chronic hypoxia.
- Examination of genetic mutations (VHL, SDHx, EPAS1) and their link to PGL.
Main Results:
- High-altitude populations show increased incidence of head and neck paragangliomas (HN-PGL), particularly in females.
- Genetic mutations in VHL, SDHx, and EPAS1 genes mimic hypoxia, promoting PGL.
- Somatic EPAS1 mutations correlate with PGL risk in hypoxemic conditions (e.g., heart disease).
Conclusions:
- Paragangliomas exhibit unique sensitivity to hypoxic signaling.
- Hypoxia, whether from high altitude, disease, or genetic mutations, is pivotal in PGL formation.
- Understanding hypoxia's role is crucial for PGL research and potential therapeutic strategies.
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