F armers and their family members are generally thought to be very healthy—after all, farming and farm life are physically demanding, and food is plentiful. Scientific research supports this belief to a certain extent:

as a group, farmers live longer and have lower death rates from heart disease and lung cancer than the general population. On the other hand, farmers have a higher risk of injury, respiratory problems and skin conditions. Some studies have also shown that farmers have a higher risk of certain types of cancer. To answer questions about the agricultural community’s health, scientists from several federal health agencies began the Agricultural Health Study in 1993. This large, long-term study examines how lifestyle habits, genetic factors, and

agricultural exposures at work and in the environment contribute to the risk of disease. Scientists from the National Cancer Institute, the National Institute of Environmental Health Sciences, and the United States Environmental Protection Agency are conducting the Agricultural

Health Study. They are collaborating with scientists at the National Institute for Occupational Safety and Health, the University of Iowa, Battelle Centers for Public Health Research and Evaluation in North Carolina and other research institutions. Certified farmer pesticide applicators and their spouses from North Carolina and Iowa and licensed commercial pesticide applicators from Iowa volun-teered to participate in this one-of-a-kind study. Thanks to the generosity of the study’s 89,658 participants, scientists have begun to better understand the relationship of pesticides, other agricultural exposures, and health. The Agricul-tural Health Study will provide information that those who work in agriculture can use in making decisions about their health and the health of their families.

About this Series

Understanding the Agricultural Health Study Part 1: Overview, Part 2: Pesticide Exposure, Part 3: Health Findings is an educational resource for the agricultural community.

The series was developed through a collaboration of North Carolina State University and Iowa State University Extension educators and Agricultural Health Study scientists and was funded by the National Institute for Occupational Safety and Health.

The Agricultural Health

Study seeks to identify factors

that promote health.

Lead scientists

• National Cancer Institute • National Institute of Environmental Health Sciences • United States Environmental Protection Agency

Collaborating scientists

• National Institute for Occupational Safety and Health • University of Iowa College of Public Health • Battelle Centers for Public Health Research and Evaluation (North Carolina)

Study design: long-term follow-up

• Begin with large group of participants • Evaluate health status into the future

Participants: certified pesticide applicators and spouses (89,658)

• North Carolina (31,094) - Farmers (20,518) and spouses (10,576) • Iowa (58,564) - Farmers (31,877) and spouses (21,771) - Commercial pesticide applicators (4,916) • Enrolled from 1993 to1997 at pesticide safety classes or at home

Collection of information

• Participants provide information about pesticide use, work habits, lifestyle habits and medical history at enrollment and periodic updates. Parents provide information on children under age 18. • Participants provide mouthwash sample (cheek cells for genetic studies) • Scientists collect information on deaths, cancers and other diseases from health databases.

Measurement of pesticide exposure (selected farms)

• Hand wipes, skin patches and air samples from farmer pesticide applicators • Urine samples from farmers, spouses, children • House dust samples

Assessment of disease rates and risk factors

• Cancers • Diseases or conditions of the immune, respiratory, reproductive and nervous systems • Other medical conditions • Cause of death or injury

Agricultural Health Study at a Glance

www.aghealth.org

HEALTH STUDY

AGRICULTURAL

Iowa andNorth Carolina

Brain and Central Nervous SystemPeripheral Nervous System

Agricultural Health Study Has Unique Strengths

The Agricultural Health Study is the largest, most comprehensive study of agricultural health ever conducted in the United States. Several features make the study unique and valuable. The study design allows scien-tists to evaluate many diseases at the same time. Because a large number of participants are enrolled, even rare diseases can be studied. Also, because a comprehensive set of information is collected and updated periodically researchers can conduct many types of health studies. Because the study started with a defined population, follows the par-ticipants into the future, and updates information every few years, the in-formation collected is of high quality. The agricultural exposure and lifestyle information is the most detailed ever collected. The Agricultural Health Study is the first study to look comprehensively at the health of women in an agricul-tural setting. Female certified pesticide applicators and women living on farms are participating in the study. The Agricultural Health Study is one of several long-term health studies to collect genetic samples. The scien-tists asked participants to provide a DNA sample using a simple technique: rinse and spit. Those who agreed to submit a genetic sample were provided mouthwash and a sample container. All they had to do was rinse their mouths with the mouthwash, spit into the container, and return the sample to the scientists. The rinse contains cheek cells from the inside lining of the mouth. Like other cells in the body, these cells contain DNA. By collecting DNA samples, scientists will be able to learn even more about the disease process, including why some people exposed to certain substances develop disease while others exposed to the same substances do not.

Other Chronic Conditions for Further Study

Immune system: Altered function, Hypersensi-tivity (contact dermatitis, asthma) Autoimmune diseases (rheumatoid arthritis, lupus)Kidney diseaseNervous system: Neurobehavioral effects, Parkinson’s diseaseReproductive effects (male and female):Infertility, Unsuccessful pregnancyRespiratory system: Reduced lung function, Asthma, Toxic dust syndromes

Farmers are healthier than the general population in some respects: they live longer and are less likely to die from heart disease than the general popula-tion. Fewer farmers die of certain cancers (lung, esophagus, bladder, and colon), probably because farmers, in general, are less likely to smoke, eat a healthy diet, and get more physical activity. However, farming is hazardous, and farmers are at high risk for injury, non-cancerous respira-tory disease, and skin problems. Farmers are exposed to hazards such as pesticides, infectious agents, naturally-produced toxins, dusts, fuels, oils, engine exhaust, fertilizers, dangerous equipment, weather extremes, sunlight and noise. According to some previous studies, farmers have higher rates of some can-cers, including Hodgkin’s disease, leuke-mia, multiple myeloma, non-Hodgkin’s

lymphoma, and cancers of the lip, stomach, prostate, skin, brain, and connec-tive tissue. Although there is uncertainty about some of these studies, scientists sus-pect that pesticides may be linked to some of these cancers. Laboratory animal studies and some human studies indicate that some farm environment exposures, mainly pesticides, may influence some non-cancer health problems of the immune system, nervous system, kidneys, respiratory system, and male and female reproductive systems. The Agricultural Health Study addresses the weaknesses and gaps in the previous population studies of pesticide exposure and human health. In addition, the study examines new information about the whole array of agricultural exposures and their relation- ship to health effects.

Previous Studies Suggest Agricultural Exposures and Health Problems Are Linked

Cancers for Further Study

BrainConnective tissues (soft tissue sarcoma)Immune system and blood:

Leukemia (bone marrow)Multiple myeloma (bone marrow)Hodgkin’s disease (lymphatic tissue) Non-Hodgkin’s lymphoma (lymphatic tissue)

Lip and skin Prostate Stomach

MaleReproductiveSystem

FemaleReproductiveSystem

Bone Marrow

RespiratorySystem

Lungs

Immune System/Blood

Immune System

Spleen

Lymphatic System

Prostate

MaleReproductiveSystem

FemaleReproductiveSystem

Bone Marrow

RespiratorySystem

Lungs

Immune System/Blood

Immune System

Spleen

Lymphatic System

Prostate

Nervous System Nervous System Brain and Central Nervous System

Peripheral Nervous System

Connective Tissues

Connective Tissues

KidneyKidney

StomachStomach

Participants Reflect North Carolina and Iowa Agriculture

By comparing agricultural census data, scientists have found that the study participants and their farms are typical of farms and farmers in North Carolina and Iowa:• Iowa’s farmers grow mainly corn and soybeans and raise hogs. • North Carolina farmers grow corn and soybeans as well as tobacco,

peanuts, cotton, and such vegetable crops as cucumbers, tomatoes and watermelon. They also raise beef, poultry, and hogs.

• Iowa farms are larger on average than North Carolina farms.• Farmers in both states are predominantly white men.• African-Americans make up a small minority of North Carolina farmers.

The Study has also learned that:• More than one-half of the farmers’ spouses report being active in farm work.• The Iowa commercial applicators were younger on average (39 years) at

enrollment than the farmer pesticide applicators (47 years). Commercial applicators report more varied pesticide application tasks than Iowa farmers.

• About 3% of pesticide applicators in the study are women.

For More Information Visit www.aghealth.org References: Alavanja, M.C.R., D.P. Sandler, S.B. McMaster, S.H. Zahm, C.J. McDonnell, C.F. Lynch, M. Pennybacker, N. Roth- man, M. Dosemeci, A.E. Bond, and A. Blair. The Agricul- tural Health Study. Environmental Health Perspectives. 104:362-9 (1996).

Prepared by: Julia F. Storm, W. Gregory Cope, and Wayne G. Buhler of North Carolina Cooperative Extension at North Carolina State University and Katherine McGinnis of the Eastern Area Health Education Center at East Carolina University.

Edited by: Dee Shore

Graphic Design by: Greg Miller, Brenda Bunch, Sandy Smith, and Dana C. Babbs

Illustrated by: Brenda Bunch and Grace Jenkins

Photos courtesy of: United States Department of Agriculture’s Natural Resources Conservation Service and the Department of CALS Commu-nication Services in North Carolina State University’s College of Agriculture and Life Sciences.

Reviewed by:Agricultural Health Study Executive Committee: Michael Alavanja, Aaron Blair, Joy Herrington, Cynthia Hines,Jane Hoppin, Charles Knott, Charles Lynch, Dale Sandler, Kent ThomasExtension Educators: Amy Brown, Roger Crickenberger, Jerry DeWitt, Bill Ellers, Mark Shour, Suzanne Snedeker, Fred WhitfordOthers: Dennis Schwab, Iowa farmer; John Acquavella, Monsanto Company; Ernest Hodgson, NC State University

Published by:North Carolina Cooperative Extension Service September 2004

100,000 copies of this document were printed at a cost of $14,760, or $0.15 per copy.

Distributed in furtherance of the Acts of Congress of May 8 and June 30, 1914. Employment and program opportunities are offered to all people regardless of race, color, national origin, sex, age, or disability. North Caro-lina State University, North Carolina A & T State University, U.S. Department of Agriculture, and local governments cooperating.

This publication series is an education project of the South-ern Coastal Agromedicine Center of the North Carolina Agromedicine Institute and was funded by a grant from the National Institute for Occupational Safety and Health.

Dr. Michael Alavanja of the National Cancer Institute (NCI) is the Director of the Agricultural Health Study. Dr. Alavanja and Dr. Aaron Blair of NCI, Dr. Dale Sandler and Dr. Jane Hoppin of the National Institutes of Environ-mental Health Sciences (NIEHS), and Mr. Kent Thomas of the United States Environmental Protection Agency (EPA) collaborate to direct the study. Ms. Cynthia Hines is the study liaison at the National Institute for Occupa-tional Safety and Health (NIOSH). NCI scientists conduct the cancer studies, while NIEHS scientists study other chronic diseases. EPA and NIOSH scientists assess pesticide exposure. University scientists and other researchers collaborate on selected projects. Study operations in North Caro-lina and Iowa are directed by Mr. Charles Knott of the Battelle Centers for Public Health Research and Evalu-ation and Dr. Charles Lynch of the University of Iowa’s College of Public Health respectively. These scientists are in charge of enrolling and com-municating with study participants in their states. They collect and man-age information from the surveys and phone interviews and collect the mouthwash samples from partici-

1993-1997 Recruit and survey participants

1998-2003 Test pesticide exposure estimates; Collect genetic sample

2004-2008 Assess disease rates and risk factors

2009-2013 Evaluate disease mechanisms

pants. They also obtain health infor-mation from state and national health statistic databases. They ensure that all information provided by or about the participants is kept secure and confidential. Project managers from Westat, Inc. coordinate study activi-ties among all of the collaborating organizations.

The scientists meet annually with advisors to discuss progress and plans. The National Advisory Panel is made up of scientists, Cooperative Exten-sion representatives, and farmers; meetings are open to the public. Simi-lar state advisory committees meet in North Carolina and Iowa.

Health Scientists Collaborate on Agricultural Health Study

Study Timeline

AG-Med-24

SOUTHERNCOASTALAGROMEDICINECENTER

SOUTHERNCOASTALAGROMEDICINECENTER

A Summary of the First 12 Years of a Long-term Study of Iowa and North Carolina Pesticide Applicators and Farm Families

6

Scientists are conducting several types of studies, focusing on the diseases that are newly diagnosed in participants after enrollment.

A primary purpose of a prospective cohort study is to determine dis-ease rates. The scientists are interested in the overall rates of cancer and the rates of particular types of cancer in the Agricultural Health Study population. After ad- justing for gender and age, they com- pare these rates to those of the general populations in North Carolina and Iowa for the same diseases. If the dis- ease occurs more often in the Agricul- tural Health Study population, they want to know why. Scientists can also determine cancer rates for participants using a particular pesticide. Scientists will use compari-sons within the cohort over time to learn about the rates of diseases other than cancer.

The scientists look for clues, or associations, about what factors may have contributed to the disease by conducting nested case-control stud-ies. The scientists closely compare the various exposures and lifestyles of people within the cohort diagnosed with the disease (cases) to those of people within the cohort without the disease (controls). A Parkinson?s disease study is under way and others are scheduled.

The scientists conduct cross-sectional studies to evaluate information about exposures and self-reported symptoms or diseases that was col-lected entirely from the participant surveys. These studies help scientists learn about many of the non-cancer health issues that aren?t tracked in databases. Scientists may follow up these studies with more in-depth case-control studies. Other cross-sectional studies will evaluate the bio-logical plausibility of health findings. These studies will collect biologic samples such as urine or blood to identify markers of exposure or early signs of disease. For example, a study of corn growers will examine measures of immune system function in blood in relation to pesticide application over a 12 month period.

To under-

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AnswersHealth findings are summarized in Understand-ing the Agricultural Health Study Part 3: Health Findings.

HEALTH STUDY

AGRICULTURAL

Iowa andNorth Carolina

www.aghealth.org

x + y = z 6

7

Our DNA serves as a genetic blueprint—the in-structions for how our bodies function, including how our bodies break down chemicals that we are exposed to. Many study participants volunteered to submit DNA samples through the quick and easy rinse-and-spit mouthwash method. Scientists will use these samples to learn more about how chemi-cal exposures lead to illness.

Every year, scientists check North Carolina and Iowa cancer registries for newly diagnosed can-cers among study participants. They also check the North Carolina and Iowa death certificate databases and the National Death Index to learn if any participants have died.

Collect exposure and health information from participants

Applicators filled out surveys at the pesticide safety class and at home; spouses filled out surveys at home or on the phone. Parents provided informa-tion about children under age 18. For

participants, every step of the process is completely voluntary. Scientists keep all information confidential and secure, reporting results only in summary form so that no individual information is ever reported. There were about 250 questions in the initial survey, including questions about:

farm-work-related exposures and practices Participants were asked details about their use of chemicals, including solvents, fertilizers and 50 specific pesticides; their method of applying pesticides; and the personal protective equipment they use. Other questions addressed exposures such as dust, infectious agents and toxins.

environmental exposures Participants were asked about their environment, such as sources of drinking water, laundry and house clean-ing practices, and home location in relation to fields, to assess any potential for harmful exposures.

lifestyle choices Participants provided infor-mation about their diet and cooking practices, smoking, alcohol consumption, and physical activity.

medical history and health status Participants gave details about their medical history: whether they or their close family members have been diagnosed with such diseases as cancer, arthritis and Parkinson’s disease; symptoms related to asthma and other respiratory problems; and symptoms like numb-ness and blurry vision. Women provided information about their menstrual cycles, pregnancies, and other aspects of their reproductive health.

1

Develop and test pesticide exposure estimates

The scientists developed a formula to estimate pesticide exposure based on participants’ pesticide use and work practices, using data from the Pesticide Handlers Exposure Database and published exposure studies as a guide. The formula estimates a level of exposure for each person in the study for each chemical they used. To test the formula scientists measured pesticide levels in urine and on skin of members of about 100 farm families before, during, and after a pesticide application. This and other pesticide exposure studies are summarized in Understanding the Agricultural Health Study Part 2: Pesticide Exposure.

Collect a genetic sample from participants

3

4

5

Analyze the exposure and health information2

Questions

Through the Agricultural Health Study, scientists are looking for answers to many questions raised about cancer and other health issues in the agricultural population. The study is a long-term follow-up study called a prospective cohort study. This means the study involves a large group of volunteer participants (the co-hort) who are followed into the future (prospective) to determine who gets sick and who does not. The scien-tists look for associations, or links, between substances the participants are exposed to and the health problems they have over time. Follow the steps the scientists take as they navigate a maze of information to discover the answers to these questions.

Enroll people into the study

The study population is North Carolina and Iowa farmers who are certified pesticide appli-cators, their spouses, and licensed commercial applicators from Iowa. About two-thirds of the 89,658 people in the study are applicators, and one-third are spouses. Farmers and com-mercial applicators volunteered to participate in the study at Cooperative Extension pesticide applicator training classes held from 1993 to 1997. Spouses enrolled through the mail or over the phone.

A g r i c u l t u r a l H e a l t h S t u d y S c i e n t i s t s N a v i g a t e a M a z e o f I n f o r m a t i o n

Collect new or updated information from participants and databases

As they follow the participants in the Agricultural Health Study into the future, scientists use periodic telephone interviews and mail surveys to collect new or updated health and exposure information. Even if applicators retire or change jobs, scientists continue to include them in the study.

A primary purpose of a long-term follow-up study is to determine disease rates, focusing on the diseases that are diagnosed in participants after enrollment. The scientists are interested in the overall rate of cancer and the rates of particular types of cancer in the Agricultural Health Study population. After adjusting for gender and age, they compare these rates to those of the general populations in North Carolina and Iowa for the same diseases. If the dis-ease occurs more of-ten in the Agricultural Health Study popu-lation, they want to know why. Scientists assess whether par-ticipants with greater exposures are associ-ated with greater risk of disease. Scientists will use comparisons within the cohort over time to learn about the rates of diseases other than cancer.

The scientists conduct cross-sectional studies to evalu-ate information about exposures and self-reported symptoms or diseases. These studies help scientists learn about many of the non-cancer health issues that aren’t tracked in databases.

Some cross-sectional studies evaluate the biological plausibility of health findings. Biologic samples such as urine or blood are collected to identify markers of exposure or early signs of disease. For example, a study of corn growers will examine measures of immune system function in relation to pesticide application over a 12 month period.

The scientists look for clues, or associations, about factors that may contribute to disease by conducting case-control studies. The scientists closely compare the various exposures and lifestyles of people in the cohort diagnosed with the disease (cases) to those of people in the cohort without the disease (controls). A Parkinson’s disease study is underway and others are scheduled.

To understand more about the role of genetics in dis-ease, scientists will conduct laboratory studies of DNA from participants who supplied mouthwash samples.

Collect information from health databases

Repeat Steps 2, 5 & 6

More Questions

PATIENT RECORD