Clinical trial NCT04260490: Multiple Myeloma and Environmental Exposure to Pesticides in the French West Indies: A Population Based Case-control Study.
Official title: Multiple Myeloma in the French West Indies. Environmental and Professional Exposure to Pesticide: A Case-control Study in Guadeloupe and Martinique
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Multiple Myeloma
Keywords: Multiple myeloma
pesticide
chlordecone
Guadeloupe
Martinique
Lead sponsor: Centre Hospitalier Universitaire de la Guadeloupe
Sponsor class: OTHER
Collaborators: name: Guadeloupe Cancer Registry
name: Martinique Cancer Registry
name: Institut National de la Santé Et de la Recherche Médicale, France
name: University of Liege
name: University Hospital Center of Martinique
name: Centre Hospitalier de Basse-Terre
First posted: 2020-02-07
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A case-control study in the general population with etiological aim, paired multicentric will be carried out. This choice is justified given the low frequency of the pathology studied in the two islands.

Cancer registries of Guadeloupe and Martinique exhaustively collect cases of multiple myeloma (MM) according to cancer registration rules established at European and international level. They have data to identify the usual places of care and diagnosis of MM in their respective territory and work in close collaboration with clinical services in charge of patients.

Brief summary: Multiple myeloma (MM) is a malignancy of plasma cells engaging in monoclonal immunoglobulin production. A strong presumption was established between exposure to pesticides and the risk of MM. The French West Indies departments of Guadeloupe and Martinique are characterized by a wide use of pesticides related to bananas plantation, particularly chlordecone which has been classified by IARC as possibly carcinogenic and has recognized hormonal properties (endocrine disruptor). The objective of this study is to measure the association between exposure to pesticide and other environmental factors in the occurrence of MM in Guadeloupe and Martinique and to estimate the proportion of cases of MM attributable to pesticide exposure. Genetic susceptibility markers and their links to environmental factors will be subsequently studies from blood samples collection.

Detailed description: Multiple Myeloma (MM) is a mature B-cell lymphoma characterized by monoclonal proliferation of tumor plasma cells invading the bone marrow. It is the second malignant hemopathy among Non-Hodgkin's Lymphomas. Etiology of the disease is poorly understood. Its higher incidence in black subjects suggests the existence of genetic factors. Numerous studies have evoked the role of exposure to environmental and occupational factors in the occurrence of MM such as exposure to pesticides, solvents, in particular benzene, and other petroleum derivatives, as well as work in an agricultural environment, in hairdressing and in the metallurgical and textile industries. According to the Collective Inserm expertise "Pesticides and Health", a strong presumption (++) has been established between exposure to pesticides and the risk of occurrence of MM.

In the French West Indies (Guadeloupe, Martinique), the incidence of MM is higher than in France. These 2 departments are characterized by a major use of pesticides in connection with the banana culture developed intensively from the 1950s. These cultures successively used organochlorine insecticides, mainly β-hexachlorocyclohexane (β-HCH), technical HCH (mixture of α, β, and γ isomers of HCH), and especially chlordecone (CLD). CLD was used from 1972 to 1993 under the trade names of Kepone® (1972-1978) and then Curlone® (1982-1993) with a CLD rate of 5%. The absence of biotic and abiotic degradation of CLD has resulted in persistent soil pollution, still present today, contamination of surface and deep waters, many plant and animal products, terrestrial and marine, and then the population. CLD is a proven carcinogen in rodents, classified as a possible carcinogen by the International Agency for Research on Cancer (IARC) and has recognized hormonal properties (endocrine disruptor). CLD has been associated with an increased risk of prostate cancer in Guadeloupe. In Martinique, a geographic correlation study has shown a high incidence of MM in individuals residing on soils polluted by CLD.

Studies on the impact of pesticides on health come up against numerous limits, in the foreground of which is the great diversity of products (more than 900 active ingredients were approved one day in France and marketed in more than 9000 different products) and the difficulty in reconstructing retrospectively and objectively the exposures of individuals due to the multiplicity of sources of exposure (leisure, gardening, domestic use).

Mode of action of pesticides is still insufficiently documented, but some are classified as genotoxic, immunotoxic, tumor promoters or endocrine disruptors. Data available in the literature mainly relate to case-control or cohort studies on the occupational exposure of agricultural workers in industrialized countries. Measurement of this exposure is mainly made from self-administered questionnaires.

The investigators propose to assess feasibility of a case-control study on role of exposure to pesticides, in particular to CLD and persistent pollutants, as well as other occupational exposures in the occurrence of MM in the West Indies. This study is part of the recommendations of the Inserm-InVs Chlordecone Scientific Council and action 18 of the National Interministerial Chlordecone Plan "initiate work on the link between myelomas and exposure to chlordecone".

Eligibility criteria: Inclusion Criteria:

* Cases :
* patients above 18 years old
* with a place of residence in Guadeloupe or Martinique
* meeting the inclusion criteria for multiple myeloma identified from hematologist, oncologist and clinicians
* who ave a written informed consent.

Controls :

* individuals selected after stratification on department of residence, sex and age of the cases
* who gave a written informed consent to participate.

Exclusion Criteria:

* Refusal to participate
* subject not affiliated to a social welfare or under guardianship
* Pregnant or lactating woman
* Subject participating in another research including an exclusion period still in progress at the pre-inclusion

Primary outcomes:
measure: Measure of association between exposure to chlordecone and risk of multiple myeloma.
timeFrame: Pesticide samples will be sent to the Reference Laboratory of Animal Ecology and Ecotoxicology in Liège once or twice a year. For a given patient, the time frame (questionnaire + and blood analyses) will be 12 months after inclusion.
Secondary outcomes:
measure: proportion of MM cases attributable to pesticide exposure
timeFrame: 36 months after first inclusion
Other outcomes:
Locations:
city: Pointe-à-Pitre
country: Guadeloupe
facility: University Hospital Center of Guadeloupe
city: Fort-de-France
country: Martinique
facility: University Hospital Center of Martinique
Study officials:
affiliation: CHU de la Guadeloupe
name: Jacqueline Deloumeaux, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Flowers CR, Glover R, Lonial S, Brawley OW. Racial differences in the incidence and outcomes for patients with hematological malignancies. Curr Probl Cancer. 2007 May-Jun;31(3):182-201. doi: 10.1016/j.currproblcancer.2007.01.005. No abstract available.
citation: Multigner L, Ndong JR, Giusti A, Romana M, Delacroix-Maillard H, Cordier S, Jegou B, Thome JP, Blanchet P. Chlordecone exposure and risk of prostate cancer. J Clin Oncol. 2010 Jul 20;28(21):3457-62. doi: 10.1200/JCO.2009.27.2153. Epub 2010 Jun 21.