Attachment 22-1 BEEA Objectives and Revisions

Attachment 22.1: Objectives and Background for the
Study of Biomarkers of Exposures and Effects in Agriculture (BEEA)

This revision is proposing the continuation of the Study of Biomarkers of Exposures and Effects
in Agriculture (BEEA). This eight-year effort has two primary objectives. First, to determine
the prevalence and study the etiology of monoclonal gammopathy of undetermined significance
(MGUS) in a sample of 2,000 cancer-free, male Agricultural Health Study (AHS) pesticide
applicators over the age of 50, with well-characterized occupational exposures and lifestyle
factors. MGUS has been recently been observed to precede all cases of multiple myeloma in the
National Cancer Institute’s Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening
trial and multiple myeloma has been observed to occur in excess in the AHS cohort. Preliminary
observations from the AHS cohort have also shown that MGUS occurs almost twice as
frequently as would be expected in a population of the same age and racial distribution in
Olmsted County, Minnesota. To achieve this objective, the prevalence of MGUS in the AHS
cohort will be compared with the prevalence in two general population-based cohorts (i.e.,
Olmsted County and NHANES III) with well-characterized MGUS prevalence levels. The
associations between MGUS and specific pesticides within the AHS cohort will be examined and
it will be determined whether selected biomarkers are associated with excess MGUS and
whether these biomarkers are significantly associated with specific pesticides.
Dust will be collected as part of BEEA for the purpose of evaluating exposures in the rural and
agricultural environment, such as endotoxins, and pesticides, which have been shown to settle in
dust. These exposures in the dust will be linked both to questionnaire data previously collected
to evaluate determinants that influence these levels in the home environment, and to various
health outcomes. The questionnaire that accompanies the collection of the dust will allow
researchers to evaluate these levels in relationship to home characteristics that may influence the
levels, and to ensure that the dust being collected is actually from the home where the participant
lives. The questionnaire questions and protocol for dust collection are based on previous NCI
studies using similar methodologies1,2.
The second objective will establish a resource with the remaining biospecimens and other
samples collected from the participants for the BEEA study that will be used to evaluate the
biological plausibility and the mechanism-of-action of associations between pesticides and other
agricultural exposures and risk of cancers observed in earlier AHS studies. Many of these
pesticides are non-genotoxic and their mechanism of carcinogenesis has not been determined.
The biospecimen resource will include blood, urine, saliva/buccal cells, and airborne dust and
1

Residential exposure to polychlorinated biphenyls and organochlorine pesticides and risk of
childhood leukemia. Ward MH, Colt JS, Metayer C, Gunier RB, Lubin J, Crouse V, Nishioka
MG, Reynolds P, Buffler PA. Environ Health Perspect. 2009 Jun;117(6):1007-13.
2

Household endotoxin levels and the risk of non-Hodgkin lymphoma. Wang J, Cozen W, Thorne
PS, Berhane K, Cerhan JR, Hartge P, Ward MH, De Roos AJ, Severson RK, Morton LM,
Bernstein L, Linet MS, Colt JS. Cancer Causes Control. 2013 Feb;24(2):357-64.

house dust samples will also be collected from some participants. We will also enroll and collect
biospecimens from an additional 200 individuals who have not lived or worked on a farm as an
adult or held a job applying pesticides; these participants will serve as controls in future crosssectional molecular epidemiologic investigations of specific agricultural exposures and
intermediate biomarkers related to cancer or other chronic diseases. The controls will be
identified from state voter registries in Iowa and North Carolina and will be frequency-matched
to BEEA participants on age, race, and state and county of residence.
Among a subset of participants in the BEEA study, we will also conduct an evaluation of the use
of smartphone technology to record daily activities (anticipated N=235). The purpose of this
effort is to characterize variability in farming activities and to provide insight into the feasibility
of using smartphones to collect exposure information for future use in prospective cohort studies.
The participants in this effort will be asked to download and use the smartphone app to document
their daily farm routine on 30 randomly selected days over a 6-month period.