### Agricultural Health Study

> In 1993, scientists from the National Cancer Institute, the National
> Institute of Environmental Health Sciences, and the U.S. Environmental
> Protection Agency began a study known as the Agricultural Health Study
> (AHS). Its goal is to follow a large cohort of men and women over time
> to evaluate the role of agricultural exposures in the development of
> cancer and other diseases in the farming community. (Agricultural
> Health Study homepage: [www.aghealth.org)]{.underline}
>
> The study also will provide an opportunity to assess the role that
> diet, cooking methods, and other lifestyle and genetic factors have on
> the cause of cancer and other diseases. The results of the study will
> provide information that can be used to create a safe work environment
> and healthy lifestyle for agricultural workers and their families.

**Study Objectives**

> Specific research goals are to:

-   Characterize the cancer risks among study participants that have
    direct exposure to pesticides\* and other agricultural agents;
    (Pesticides include fungicides, herbicides, and insecticides\*\*.)

-   Characterize the non-cancer risks, such as asthma and other
    respiratory diseases, neurologic diseases, including Parkinson's,
    reproductive defects including birth and developmental defects in
    children, kidney disease, and autoimmune diseases, including
    arthritis among study participants that have direct exposure to
    pesticides and other agricultural agents;

-   Characterize the disease risks among spouses and children of farmers
    that may arise from both direct and indirect contact with pesticides
    and agricultural chemicals used in the home;

-   Define specific work practices associated with high levels of
    pesticide and other agricultural exposures;

-   Define biomarkers that may be used to monitor exposure to pesticides
    and other agricultural agents;

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-   Measure the degree of pesticide exposure among farmers and their
    families, particularly children.

-   Investigate interactions between specific gene alterations and
    pesticide exposures that lead to increased disease susceptibility;

-   Characterize the role of diet and lifestyle factors in development
    of cancer and other diseases among this population.

> \* pesticides are agents used to control pests of any sort.
>
> \*\* fungicides are agents that control fungi; herbicides are agents
> that control weeds; and insecticides are agents that control insects.

# Background 

> Farmers in many countries, including the U.S. have lower over-all
> death rates and cancer rates than the general population. Lower
> mortality rates among farmers for heart disease and cancers of the
> lung, esophagus, bladder and colon, in particular, are thought to be
> due to lower smoking rates, as well as physically active lifestyles
> and dietary factors.
>
> However, compared to the general population, the rates for certain
> diseases appear to be higher among agricultural workers. For example,
> asthma, neurological diseases, and spontaneous abortions may be
> related to agricultural exposures. Farming communities also often have
> higher rates of leukemia, non-Hodgkin\'s lymphoma, multiple myeloma,
> soft-tissue sarcomas, and cancers of the skin, lip, stomach, brain,
> and prostate. The rates for several of these tumors (i.e.,
> non-Hodgkin\'s lymphoma, multiple myeloma, skin, brain, and prostate)
> also appear to be increasing in the general population.
>
> Even though no one set of risk factors explains the higher cancer
> rates, the range of environmental exposures in the farming community
> are of concern. Farmers, farm workers, and farm family members may be
> exposed to substances such as pesticides, engine exhausts, solvents,
> dusts, animal viruses, fertilizers, fuels, and specific microbes that
> may account for these elevated rates. However, human studies published
> to date, have not allowed researchers to sort out which of these
> factors are linked to which cancers.

##  Study Population

The vast majority of the nearly 90,000 participants in the Agricultural
Health Study are either farmers or wives of farmers; about 50,000 are
farmers and 32,000 wives of farmers. All were recruited in North
Carolina or Iowa.

> Those called 'private pesticide applicators' are farmers or
> nursery-workers; out of the approximately 52,000 private applicators,
> about 2,000 are nursery-workers.
>
> The study includes a small percentage of 'commercial pesticide
> applicators' from Iowa who work for pest control companies or for
> businesses such as warehouses or grain mills that use pesticides
> regularly; about 5,000 are commercial applicators.
>
> The entire AHS cohort includes about 50,000 farmers, 32,000 wives of
> farmers, 2,000 nursery workers, and 5,000 commercial pesticide
> workers. Children of farm families are also included in some of the
> studies.

# Data Collection

> During the initial recruitment from 1993 through 1997 (Phase I),
> participants completed a questionnaire about pesticide use, crops
> grown, livestock raised, personal protective equipment used, pesticide
> application methods employed, other agricultural exposures such as
> solvents, grain dusts, and welding fumes, work practices that effect
> exposures, and non-farm activities that may affect either exposure or
> disease risks (e.g., diet, exercise, alcohol consumption, medical
> conditions, family history of cancer, other occupations, and smoking
> history).
>
> Phase II of the study from 1999-2003, consists of data collection and
> determination of mortality and cancer incidence among participants.
> The specific components were:

-   Computer-assisted telephone interview (CATI): These interviews are
    designed to obtain information on pesticide use since enrollment,
    changes in health status, and detailed information on farming and
    work practices.

-   Mailed Dietary Health Questionnaire: This questionnaire is designed
    to provide detailed information on cooking practices and diet.

-   Buccal (cheek) cell collection: Buccal cell collection allows
    scientists to determine whether specific genetic alternations found
    in the DNA in cheek cells, play a role in agricultural exposures and
    disease susceptibilities.

-   Determining which participants developed cancer by contacting the
    cancer registries in each state.

-   Determining which participants died by contacting the U.S. National
    Death Index (NDI), a computerized index of death record information
    collected from all State vital statistics offices and available to
    scientists for medical and health research.

> Phase III follow-up is scheduled to begin in 2004 and conclude in
> 2008. It will include the collection of additional data on diseases
> acquired by the participants, additional agricultural exposures, and
> continued tracking of mortality and cancer incidence among
> participants.
>
> In addition, a series of smaller studies focus on the risk factors for
> specific diseases. These may involve additional questionnaires and the
> collection of blood, tumor, or urine samples.

## Selected Results/Publications

-   **The principal investigators of the Agricultural Health Study
    provide a detailed summary of the goals, methods, types of studies,
    advisory groups, recruitment efforts, and a description of the
    participants enrolled after the first year of recruitment.**

> *Reference:* Alavanja MCR, Sandler DP, McMaster SB, Zahm SH, McDonnell
> CJ, Lynch CF, et al. The Agricultural Health Study. Environmental
> Health Perspective 1996;104:362

-   **In a pilot study, researchers evaluated exposure to pesticides
    through the diet for farmers and their families on six farms in Iowa
    and North Carolina. The results show that dietary exposures to
    pesticides may exceed expected values, particularly to the
    pesticides being applied and to the persistent pesticides in the
    environment.**

> The analytical methods used were capable of measuring 29 of the 33
> targeted Agricultural Health Pilot Study
>
> pesticides in dietary samples. Collections of dietary samples were
> made during a pesticide application and non-application monitoring
> period, and levels of pesticides in the foods and beverages of the
> participants were quantified in both the Iowa and North Carolina
> farms. Increased levels of the pesticide being applied during the
> monitoring period were found in the applicator\'s meal. Dieldrin was
> persistent in the foods consumed on one Iowa farm. No pesticides were
> found in drinking water samples.
>
> *Reference:* Melnyk LJ, Berry MR, Sheldon LS. Dietary exposure from
> pesticide application on farms in the Agricultural Health Pilot Study.
> J Expo Anal Environ Epidemiol 1997 Jan-Mar;7(1):61-80.
>
> .

-   **Researchers found that the wives and children of farmers or
    pesticide applicators have many opportunities for exposure to
    pesticides.**

> Twenty-one percent of the farmers' homes are within 50 yards of the
> pesticide mixing area, 27% of applicators store pesticides in their
> homes (including attached garage or basements), and most
> pesticide-contaminated clothing is washed in the same machine as other
> laundry. Furthermore, at least half of the wives reported working the
> fields, 40% reported mixing or applying pesticides, and more than half
> of the children over age 11 did farm chores that potentially put them
> into contact with pesticides.
>
> *Reference:* Gladen BC, Sandler DP, Zahm SH, Kamel F, Rowland AS,
> Alavanja MCR. Exposure opportunities of families of farmer pesticide
> applicators. American Journal of Industrial Medicine 1998;34:581-587

-   **Approximately fourteen percent of licensed pesticide applicators
    in the Agricultural Health Study reported having had an event that
    led to a relatively high exposure to pesticides during their working
    life. These exposures can result from pesticide spills, equipment
    maintenance accidents, accidental immersions, or certain spot
    spraying operations.**

> Work practices with a high exposure event included delay in changing
> clothing or washing after pesticide application, mixing pesticide
> application clothing with the family wash, washing up inside the house
> after application rather than outside the house, applying pesticides
> within 50 yards of the home well, and storing pesticides in the home.
> Job characteristics more common among those with a high pesticide
> exposure event included self-repair of pesticide application equipment
> and the first use of pesticides more than 10 years ago. Scientists
> with the Agricultural Health Study are now taking the next steps to
> understand whether these exposure events are associated with ill
> health and disease.
>
> *Reference:* Alavanja MCR, Sandler DP, McDonnell CJ, Mage DT, Dross
> BC, Rowland AS, Blair A. Characteristics of persons who self-reported
> a high pesticide exposure event in the Agricultural Health Study.
> Environmental Research 1999: 80(2):180-186.

-   **Exposure to some fungicides and insecticides may increase the risk
    of retinal degeneration.**

> Researchers compared pesticide use in 154 participants who reported
> retinal degeneration to 17,804 controls. They found that participants
> using fungicides had about an 80% greater risk of retinal degeneration
> than non-users. The risk increased with total days of fungicide use,
> and was greater when application methods involving greater personal
> exposure were used. Retinal degeneration was also related to use of
> organochlorine or carbamate insecticides, but these associations were
> less consistent.
>
> *Reference:* Kamel F, Boyes WK, Gladen BC, Rowland AS, Alavanja MC,
> Blair A, Sandler DP. Retinal degeneration in licensed pesticide
> applicators. Am J Ind Med 2000 Jun;37(6):618-28.

-   **Pesticides may contribute to respiratory symptoms among farmers.**

> A total of 20,468 pesticide applicators, ranging in age from 16 to 88
> years, provided complete information on 40 currently used pesticides
> and pesticide application practices. 19% reported wheezing in the past
> year. Five pesticides were suspected to contribute to wheeze:
> paraquat, three organophosphates (parathion, malathion, and
> chlorpyrifos), and one thiocarbamate (S-ethyl-dipropylthiocarbamate
> \[EPTC\]). Parathion had the strongest association and chlorpyrifos,
> EPTC, paraquat, and parathion demonstrated significant dose-response
> trends. The herbicides, atrazine and alachlor, but not 2,4-D, were
> associated with wheeze. Atrazine had a significant dose-response
> trend. These associations, though small, suggest an independent role
> for specific pesticides in respiratory symptoms of farmers.
>
> *References:* Hoppin JA, Umbach DM, London SJ, Alavanja MC, Sandler
> DP. Chemical predictors of wheeze among farmer pesticide applicators
> in the Agricultural Health Study. Respir Crit Care Med 2002 Mar
> 1;165(5):683-9

-   **Researchers estimated the prevalence of exposure to various
    chemical, physical, and biological agents in over 52,000 licensed
    pesticide applicators from North Carolina and Iowa, who were mostly
    farmers.**

> Twenty-five percent were exposed to solvents, 68 percent metals, 65
> percent grain dusts, and 93 percent diesel exhaust fumes. Most of the
> farmers reported performing routine maintenance tasks at least once a
> month, such as painting (63%), welding (64%), and repair of pesticide
> equipment (58%). The majority of farmers (74% in North Carolina; 59%
> in Iowa) reported holding non-farm jobs; the most frequent were
> construction and transportation. The majority of the farmers enrolled
> in the AHS (55%) also reported that they mixed or applied pesticides
> on 10 or more days per year.
>
> *Reference:* Coble J, Hoppin JA, Engel L, Elci OC, Dosemeci M, Lynch
> CF, Alavanja M. Prevalence of exposure to solvents, metals, grain
> dust, and other hazards among farmers in the Agricultural Health
> Study. J Expo Anal Environ Epidemiol 2002;12(6):418-26.

-   **Black farmers reported lower lifetime pesticide use, less use of
    each class of pesticides (e.g., herbicides, insecticides), less use
    of high exposure application methods, and fewer pesticide-related
    symptoms such as headaches or dizziness, skin irritation, chest
    discomfort and feeling nervous or depressed than did white
    farmers.**

> Health effects of pesticides have not been well studied in black
> farmers. The researchers described agricultural practices and
> pesticide-related symptoms in North Carolina black and white farmers
> participating in the Agricultural Health Study. Despite lower use of
> pesticides, black farmers may have other work practices that affect
> exposure and risk.
>
> *Reference:* Martin SA Jr, Sandler DP, Harlow SD, Shore DL, Rowland
> AS, Alavanja MC. Pesticide use and pesticide-related symptoms among
> black farmers in the Agricultural Health Study. Am J Ind Med 2002
> Mar;41(3):202-9.

-   **Researchers analyzed the risk factors that may account for
    machinery-related injuries among Iowa farmers.**

> Farm machinery is a major cause of injury and death among farmers.
> Researchers identified 205 farmers who had machinery-related injuries
> requiring medical advice/treatment in the previous year. Several
> possible risk factors for injury were analyzed by comparing these
> farmers to 473 farmers who had no injury in the previous year.
> Analysis showed significant associations between machinery-related
> injury and hours per week spent on farm-work, fewer years of farming
> experience, wearing a hearing aid, and a high CAGE score suggesting
> problem drinking.
>
> *Reference:* Sprince NL, Park H, Zwerling C, Lynch CF, Whitten PA, Thu
> K, Gillette PP, Burmeister LF, Alavanja MC. Risk factors for
> machinery-related injury among Iowa farmers: a case-control study
> nested in the Agricultural Health Study Int J Occup Environ Health
> 2002 Oct-Dec;8(4):332-8.

-   **Researchers analyzed the risk factors that may account for
    large-livestock (hogs, cattle, horses, or sheep) related injuries.**

> Researchers identified 116 farmers with large livestock who had an
> animal-related injury requiring medical advice or treatment in the
> previous year. Several possible risk factors for injury were analyzed
> by comparing these farmers to 342 farmers who had livestock, but were
> not injured in the previous year. Significant associations between
> animal-related injuries and use of a hearing aid, doctor-diagnosed
> arthritis or rheumatism, education beyond high school, and a younger
> age were found.
>
> *Reference:* Sprince NL, Park H, Zwerling C, Lynch CF, Whitten PS, Thu
> K, Burmeister LF, Gillette PP, Alavanja MCR. Risk factors for
> animal-related injury among Iowa large-livestock farmers: a
> case-control study nested in the Agricultural Health Study. Journal of
> Rural Health 2003;19(2):165-173.

-   **Researchers found that pesticide applicators have a small but
    significantly higher rate of prostate cancer than the general
    population. Among the 45 specific pesticides evaluated, only one,
    methyl bromide was linked to the risk of prostate cancer. Six others
    (chlorpyrifos, coumaphos, fonofos, phorate, permethrin, and
    butylate) showed an increased risk of prostate cancer among men with
    a family history of prostate cancer, but not among those with no
    family history.**

> The 14% increased risk of prostate cancer among pesticide applicators
> supports previous studies showing farming to be the most consistent
> occupational risk factor for prostate cancer. The increased risk
> associated with methyl bromide, an alkylating agent and fumigant used
> nationally to protect crops from pests found in the soil, and to
> fumigate grain silos, is a novel finding. The scientists found that
> the risk of prostate cancer increased with increasing frequency of
> use, and longer lifetime exposure, and was seen among both North
> Carolina and Iowa pesticide applicators. Based on animal studies,
> methyl bromide is listed by the National Institute for Occupational
> Safety and Health (NIOSH) as a potential occupational carcinogen.
>
> Five out of the six chemicals linked to an increased risk of prostate
> cancer in men with a family history of prostate cancer, have a similar
> chemical structure (thiophosphates). This implies that the pesticides
> may be interacting with a particular genetic abnormality to increase
> the risk of developing prostate cancer in these men. This interaction
> will be the topic of future research.
>
> *Reference:* Alavanja MCR, Samanic C, Dosemeci M, Lubin J, Tarone R,
> Lynch CF, et al. Use of agricultural pesticides and prostate cancer
> risk in the Agricultural Health Study cohort. Am J Epidemiol
> 2003;157:800-814.