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

NCT02727868 | Completed

• 2 other identifiers: 2015-422015-A01753-46
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Patient With Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (2)

exclusive breast irradiation group

OTHER

to assess the impact of irradiation areas

Genetic: blood samples

breast and sternal irradiation group

OTHER

to assess the impact of irradiation areas

Genetic: blood samples

Interventions

blood samples GENETIC

breast and sternal irradiation group; exclusive breast irradiation group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique Hôpitaux de Marseille

Marseille, 13354, France

Location

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2016
• First Posted: April 5, 2016
• Study Start: March 3, 2016
• Primary Completion: June 2, 2017
• Study Completion: June 2, 2017
• Last Updated: October 30, 2023

Record last verified: 2023-10

Locations

FR (1)