Specimen Collection for Agricultural Health Study Cohort Pesticide Exposure Study
Condition: Multiple Myeloma; Leukemia; MGUS; Monoclonal B-Cell Lymphocytosis
MeSH terms: Multiple Myeloma; Lymphocytosis
Study type: Observational

Summary: 
      Background:

      - Multiple myeloma (MM), a type of cancer that affects the white blood cells, is often
      preceded by a precancerous disorder known as monoclonal gammopathy of undetermined
      significance (MGUS). Farmers and other agricultural workers have a higher risk of developing
      MGUS and MM, possibly because of their exposure to certain pesticides. Researchers are
      interested in studying biological specimens taken from participants in the Agricultural
      Health Study - specifically, pesticide applicators at least 50 years of age who do not have
      cancer- to better understand the development of MGUS and MM.

      Objectives:

        -  To collect biological specimens from Agricultural Health Study participants for further
           research.

        -  To examine the relationship between pesticide exposure and MGUS/MM.

      Eligibility:

      - Male pesticide applicators who are over 50 years of age, cancer-free, and participating in
      the Agricultural Health Study.

      Design:

        -  Two groups of participants will complete the study: a general group and a smaller group
           of individuals who have been exposed to the pesticide diazinon.

        -  All participants will receive an initial contact letter with information about the
           study, followed by a phone call to administer a screening questionnaire and arrange a
           home visit from a researcher within the next month.

        -  Participants will receive by mail a urine specimen kit that will be collected at the
           home visit.

        -  During the home visit, a study researcher will take blood samples and collect the urine
           sample, and will administer another questionnaire.

        -  Participants in the group exposed to diazinon will have three home visits for the study:
           (1) prior to pesticide exposure, (2) the day after participants stop using diazinon, and
           (3) about 21 days after the second visit. The first visit will take place in the
           off-season from January to March; the second and third visits will be conducted between
           April and August.

        -  No treatment will be provided as part of this study.
    

Detailed description: 
      We propose to conduct a molecular epidemiology study with a subset of participants in the
      Agricultural Health Study (AHS), a prospective cohort of 57,310 licensed pesticide
      applicators in Iowa and North Carolina. Blood and urine samples will be collected from 1,990
      cancer-free male AHS participants over the age of 50. These participants will also be asked
      to complete a brief interview (approximately 20 minutes) regarding recent exposures and other
      lifestyle and health characteristics, which will be conducted at the time of the biospecimen
      collection. Participants in both Iowa and North Carolina will be enrolled and home visits for
      interviews and sample collection will take place throughout the year between 2010-2014.

      The proposed study has two primary objectives. First, we will determine the prevalence and
      study the etiology of monoclonal gammopathy of undetermined significance (MGUS), which is a
      precursor biomarker for multiple myeloma. We will compare the prevalence of MGUS in the AHS
      cohort with the prevalence in two general population-based cohorts ( i.e., Olmsted County and
      NHANES IID) with well-characterized MGUS prevalence levels. As a result of previous data
      collection efforts in the AHS, comprehensive information on lifetime occupational exposures
      and lifestyle factors will be available for the subjects included in this study. We will
      examine the associations between MGUS and lifetime exposure to specific pesticides within the
      AHS cohort. We will also evaluate several other biomarkers, including telomere length and
      global DNA hypomethylation in peripheral blood lymphocytes, for associations with specific
      pesticides and excess risk of MGUS.

      The second objective is to establish a resource with the remaining blood and urine samples
      collected from the participants in this study. These biospecimens will be used to evaluate
      the biological plausibility and the mechanism-of-action of associations between pesticides
      and cancers observed in earlier AHS studies. Many of these pesticides are non-genotoxic and
      their mechanism of carcinogenesis has not been determined. One such future study involving
      repository samples will be an investigation of monoclonal B-cell lymphocytosis (MBL), a
      marker which has been shown to precede chronic lymphocytic leukemia in previous studies.
      Several pesticides in current widespread use in the AHS have been linked to leukemia. We will
      determine the prevalence of MBL in the AHS cohort and evaluate potential associations with
      specific pesticides of interest to better explain the relation between pesticide exposures
      and leukemia risk.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Male pesticide applicators who are over 50 years of age, cancer-free, and participating in
        the Agricultural Health Study. Plus, a small control group comprising individuals who have
        not worked in agriculture or been occupationally exposed to pesticides.
      
Keywords: Multiple Myeloma; MGUS; Leukemia; Biorepository; Natural History