Assessment of the Mutation of Pig-A Gene as Biomarker of Genotoxic Exposure in Humans (PIG-A)

The evaluation of the impact of environment on the incidence of cancer is a major public health issue. Increased knowledge in this area is necessary for the implementation of primary prevention means with appropriate preventive measures but also to the implementation of secondary prevention measures with targeted screening actions.

Among the environmental exposures that may lead to cancer, mutagenic environments are of major importance, and the causal link between environmental genotoxicity and cancer has been established for a long time. It is also well established that susceptibility to mutation is highly variable among individuals. This is explained by genetic polymorphisms of genes involved in metabolism and in genome stability.

The identification of biomarkers of exposure to mutagenic environments is necessary for assessing the impact of an environment in humans. Some studies in animals have shown that the PIG-A gene may be a biomarker of exposure to a mutagenic environment. In particular, a significant increase in erythrocyte PIG-A mutants has been demonstrated in rats after a genotoxic exposure to cisplatin, but it has so far not been evaluated in humans. One study of healthy volunteers shows that the frequency of PIG-A mutated cells in humans can be estimated efficiently and reliably.

The PIG-A gene meets all the necessary criteria for a sentinel gene for tracking of spontaneous somatic mutation frequency or induced a mutagenic environment: ubiquitous expression, phenotypic change linked to a mono-allelic mutation viability of mutated cells , spectrum off inactivating mutations (deletions, substitutions, chromosomal rearrangements). Finally, the detection of the disappearance of glycosylphosphatidylinositol on the plasma membrane is easily achievable by flow cytometry.

Study Overview

• Status: Completed
• Conditions: Patient With Breast Cancer
• Intervention / Treatment: Genetic: blood samples

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13354
    • Assistance Publique Hopitaux de Marseille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Major patients,
• The patients achieving a breast cancer
• Patients who have benefited from a breast surgery
• Patients to have an external adjuvant radiotherapy.
• Patients being able to read and understand French.
• Patients beneficiaries of a social security scheme.
• Pregnant women can not participate in this study. A pregnancy test should only be prescribed when clinically indicated, regardless of the course of the study.
• Patients who received information and signed informed consent

Exclusion Criteria:

Patients who received chemotherapy before radiation therapy.

• Minor patients
• Patients who do not speak French and / or unable to read and understand French.
• Patients who have had radiotherapy history
• Patients who have had a history of chemotherapy
• Patients who have not received the information and had not signed informed consent for participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: exclusive breast irradiation group; to assess the impact of irradiation areas	Genetic: blood samples
Other: breast and sternal irradiation group; to assess the impact of irradiation areas	Genetic: blood samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
analysis of the frequency of granulocytes PIG-A mutated	The analyzes will be applied at T0 to determine the intra-assay reproducibility. The frequency distributions of mutated cells will be compared: Between the two groups of patients at T0 then,; Within each group between T0 (before exposure), T1 (in process), T2 (end of treatment) and T3 (in therapeutic monitoring post) using non-parametric tests on paired and unpaired.	24 months
analysis of the binucleated cell micronuclei frequency in culture	Determining the frequency of micronucleated binucleate cells in culture will be performed on the samples at T0 and T3 each patient of both groups. The frequency distribution of micronucleated cells will be compared within each group between T0 and T3 using non-parametric tests on paired series. A difference shall be considered significant if p <0.05.	24 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2016
• Primary Completion (Actual): June 2, 2017
• Study Completion (Actual): June 2, 2017

Study Registration Dates

• First Submitted: March 30, 2016
• First Submitted That Met QC Criteria: March 30, 2016
• First Posted (Estimated): April 5, 2016

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 2015-42; 2015-A01753-46 (Registry Identifier: ID RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED