Study on the Incidence of Malignant Neoplasms in Patients with Parkinson's Disease and Heterozygous Mutation of the GBA Gene (ONCOGBA)

This multicenter retrospective observational study investigates the incidence of malignant neoplasms in Parkinson's disease (PD) patients carrying heterozygous pathogenic variants in the GBA1 gene. The study compares these patients to individuals with idiopathic PD and to the general population within a large national cohort.

The rationale for the study lies in the growing evidence indicating an increased risk of malignant neoplasms in patients affected by Gaucher disease.

The primary objective is to assess whether PD patients with GBA1 mutations have a higher incidence of malignant neoplasms compared to the general population. Secondary objectives include comparing the incidence of malignant neoplasms between GBA1-PD and idiopathic PD patients, as well as between idiopathic PD patients and the general population. Additionally, the study aims to characterize oncological conditions by sex, age, center, and tumor site, with specific attention to distinguishing hematologic tumors from solid tumors.

By identifying potential associations between GBA1 mutations and malignancies in PD, the findings could guide more comprehensive patient management, including screening for malignant neoplasms alongside Parkinson's disease care.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Parkinson's Disease (PD)

Detailed Description

The study will involve a network composed by different Italian Movement Disorders Centres and the corresponding local cancer registries, responsible for the active collection of cancer cases. Data will be collected from approximately 3000 consecutive Parkinson's disease (PD) patients, including about 500 patients carrying GBA1 mutations and 2500 idiopathic PD. Data about the presence of malignancies will be extracted from the Local Cancer Registries for each patient.

• Study Type: Observational
• Enrollment (Estimated): 3000

Contacts and Locations

• Study Contact: Name: Franco Valzania, MD; Phone Number: +39 0522 296494; Email: franco.valzania@ausl.re.it

Study Locations

• Italy
  • Brindisi, Italy
    • Recruiting
    • Ospedale A. Perrino
    • Contact: Francesca Spagnolo, MD; Email: francesca.spagnolo@asl.brindisi.it
    • Contact: Francesca Spagnolo, MD
  • Milano, Italy
    • Recruiting
    • IRCCS Istituto Neurologico Carlo Besta
    • Contact: Roberto Cilia, MD; Email: roberto.cilia@istituto-besta.it
    • Contact: Roberto Cilia, MD
  • Reggio Emilia, Italy, 42123
    • Recruiting
    • Azienda USL IRCCS Di Reggio Emilia
    • Contact: Franco Valzania, MD
    • Contact: Giulia Toschi, Clinical Research Coordinator; Phone Number: +390522295565
  • Trento, Italy
    • Recruiting
    • Ospedale Santa Chiara Di Trento
    • Contact: Maria Chiara Malaguti, MD; Email: mariachiara.malaguti@apss.tn.it
    • Contact: Maria Chiara Malaguti, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants will be selected from a network of Italian neurology centers with extensive experience in studying GBA-associated PD, in collaboration with local cancer registries. The study will include approximately 3,000 consecutive PD patients, subdivided into 500 patients with GBA mutations and 2,500 patients with idiopathic PD.

These participants will be compared with data from cancer registries to investigate potential associations between GBA mutations and malignancies. The population is drawn from specialized movement disorder centers and represents a clinically well-characterized cohort with access to standardized diagnostic and follow-up procedures.

Description

Inclusion Criteria:

• >18 years
• Diagnosis of Parkinson's Disease through the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Criteria for Parkinson's Disease.

Exclusion Criteria:

• Uncertain diagnosis

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
GBA-PD Cohort; Parkinson's disease (PD) patients diagnosed based on the "United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Criteria". Patients in this group must have a documented heterozygous pathogenic variant in the GBA1 gene.
Idiopathic PD Cohort; This cohort includes patients diagnosed with Parkinson's disease (PD) based on the "United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Criteria". Patients in this group do not have any documented heterozygous pathogenic variants in the GBA1 or LRRK2 genes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Increased Incidence of Malignant Neoplasms in Parkinson's Disease Patients with GBA1 Mutation Compared to the General Population	The incidence of malignant neoplasms in Parkinson's disease (PD) patients carrying the GBA1 mutation (GBA1-PD) will be calculated and compared to that of the general population to assess any potential increase in risk.	From birth to a maximum of 36 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Increased Incidence of Malignant Neoplasms in Parkinson's Disease Patients with GBA1 Mutation Compared to Non-Genetic Parkinson's Disease Patients	The incidence of malignant neoplasms in Parkinson's disease (PD) patients carrying the GBA1 mutation (GBA1-PD) will be compared to that of idiopathic PD patients using a Chi-Square test to evaluate statistical significance	From birth to a maximum of 36 months after enrollment
Evaluation of Increased Incidence of Malignant Neoplasms in Idiopathic Parkinson's Disease Patients Compared to the General Population	The incidence of neoplasms in patients with idiopathic Parkinson's disease (PD) will be compared to that of the general population.	From birth to a maximum of 36 months after enrollment
Description of Oncological Condition Incidence by Sex, Age, Center, and Tumor Site, with Specific Focus on Hematologic Versus Solid Tumors	Logistic regression analysis will be conducted to evaluate the association between neoplasms and PD subgroups (GBA1 and idiopathic PD), accounting for clinical and demographic covariates.	From birth to a maximum of 36 months after enrollment

Collaborators and Investigators

• Sponsor: Azienda Unita Sanitaria Locale Reggio Emilia

Publications and helpful links

General Publications

• Stirnemann J, Belmatoug N, Camou F, Serratrice C, Froissart R, Caillaud C, Levade T, Astudillo L, Serratrice J, Brassier A, Rose C, Billette de Villemeur T, Berger MG. A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. Int J Mol Sci. 2017 Feb 17;18(2):441. doi: 10.3390/ijms18020441.
• Mistry PK, Taddei T, vom Dahl S, Rosenbloom BE. Gaucher disease and malignancy: a model for cancer pathogenesis in an inborn error of metabolism. Crit Rev Oncog. 2013;18(3):235-46. doi: 10.1615/critrevoncog.2013006145.

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: January 29, 2025
• First Submitted That Met QC Criteria: February 5, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 7, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Neoplasms; Parkinson's Disease; GBA1; Genetic Parkinson's Disease
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Neoplasms; Parkinson Disease
• Other Study ID Numbers: 133/2023/OSS/AUSLRE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No