The ONCOGBA study (NCT06814431) is an observational retrospective cohort study designed to investigate whether heterozygous GBA1 mutations increase the incidence of malignant neoplasms in Parkinson's disease patients compared to both idiopathic PD patients and the general population. Sponsored by Azienda USL IRCCS di Reggio Emilia in Italy, this study leverages the Italian movement disorder registry to construct a large cohort of approximately 3,000 PD patients for rigorous epidemiological analysis.
This study addresses a critical knowledge gap at the intersection of lysosomal dysfunction, neurodegeneration, and oncogenesis — a triad that has attracted increasing research attention since the discovery that GBA1 mutations confer both PD risk and may modify cancer susceptibility.
| Attribute | Value |
|---|---|
| NCT Number | NCT06814431 |
| Official Title | Study on the Incidence of Malignant Neoplasms in Patients with Parkinson's Disease and Heterozygous Mutation of the GBA Gene |
| Acronym | ONCOGBA |
| Status | Recruiting |
| Study Type | Observational |
| Design | Retrospective Cohort |
| Enrollment | 3,000 participants (estimated) |
| Sponsor | Azienda USL IRCCS di Reggio Emilia |
| Conditions | Idiopathic Parkinson's Disease, GBA1-associated Parkinson's Disease |
| Start Date | November 23, 2023 (actual) |
| Primary Completion | December 2025 (estimated) |
| Completion | September 2026 (estimated) |
| Last Verified | February 2025 |
| Central Contact | Franco Valzania, MD — +39 0522 296494 |
The link between GBA1 mutations and cancer risk emerges from the fundamental role of glucocerebrosidase (GCase) in lysosomal function and cellular homeostasis[1][2]:
Lysosomal dysfunction is a shared feature of both Gaucher disease pathogenesis and PD neurodegeneration. When GCase activity is impaired, glucosylceramide and related sphingolipids accumulate within cells. This accumulation affects multiple cellular processes:
Prior studies have suggested a bidirectional relationship between PD and cancer, with GBA1 mutations potentially modulating this relationship[3]:
Understanding why GBA1 mutations might increase malignancy risk involves several interconnected pathways[4][5]:
The ONCOGBA study employs a retrospective cohort design using the Italian movement disorder registry:
┌─────────────────────────────────────────────────────────────────┐
│ Italian Movement Disorder Centers (4 Sites) │
│ Consecutive PD Patients (2020–2025) │
│ │
│ ┌──────────────────────────┐ ┌──────────────────────────┐ │
│ │ GBA-PD Cohort │ │ Idiopathic PD Cohort │ │
│ │ Heterozygous GBA1 │ │ No GBA1/LRRK2 │ │
│ │ pathogenic variant │ │ mutations │ │
│ │ ~500 patients │ │ ~2,500 patients │ │
│ └──────────┬───────────────┘ └──────────┬───────────────┘ │
│ │ │ │
│ └───────────────┬───────────────┘ │
│ ▼ │
│ Comparison against General Population │
│ Cancer Incidence Data (Italian Cancer Registries) │
└─────────────────────────────────────────────────────────────────┘
All patients are diagnosed using the UK Parkinson's Disease Society Brain Bank Diagnostic Criteria, ensuring diagnostic accuracy and consistency across all four recruiting sites.
| Arm | Description | Expected Size |
|---|---|---|
| GBA-PD | PD patients with documented heterozygous pathogenic GBA1 variant | ~500 |
| Idiopathic PD | PD patients without GBA1 or LRRK2 pathogenic mutations | ~2,500 |
"Evaluation of Increased Incidence of Malignant Neoplasms in Parkinson's Disease Patients with GBA1 Mutation Compared to the General Population"
This endpoint requires:
| Site | City | Role |
|---|---|---|
| Ospedale A. Perrino | Brindisi, Italy | Clinical assessment, genetic sampling |
| IRCCS Istituto Neurologico Carlo Besta | Milan, Italy | Clinical assessment, genetic sampling, data coordination |
| Azienda USL IRCCS di Reggio Emilia | Reggio Emilia, Italy | Lead site, sponsor, data management |
| Ospedale Santa Chiara di Trento | Trento, Italy | Clinical assessment, genetic sampling |
Franco Valzania, MD
All patients undergo comprehensive genetic screening for GBA1 mutations using:
The ONCOGBA study will provide the first large-scale, systematic evaluation of cancer risk in GBA-PD patients:
Positive findings would:
The ONCOGBA study complements interventional GBA-PD trials by addressing an important epidemiological question:
| Trial Focus | Example | Study Type |
|---|---|---|
| GCase enhancement | NCT05778617 (Ambroxol UCL) | Interventional |
| Substrate reduction | NCT04154077 (Venglustat) | Interventional |
| Gene therapy | NCT05424306 (PR001) | Interventional |
| Cancer epidemiology | NCT06814431 (ONCOGBA) | Observational |
The ONCOGBA study findings will inform other GBA-PD research by:
Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson's disease. Transl Neurodegener. 2024. ↩︎
Lysosomal dysfunction in GBA-associated Parkinsonism: From mechanisms to therapy. Nat Rev Neurol. 2025. ↩︎
Blook R, et al. GBA1 mutations and cancer risk in Parkinson's disease: A systematic review and meta-analysis. J Neurol. 2024. ↩︎
Pavan E, et al. Lysosomal dysfunction and carcinogenesis: Shared pathways between Gaucher disease and Parkinson's disease. Cell Death Discov. 2023. ↩︎
Chen Y, et al. GBA1 deficiency promotes tumor growth in models of neurodegeneration. EMBO Mol Med. 2022. ↩︎