Environmental Health Perspectives Volume
103, Supplement 8, November 1995
[Citation
in PubMed]
Agricultural Exposures and Cancer
Aaron Blair and Shelia Hoar Zahm
Occupational Studies Section, National Cancer Institute, Bethesda, Maryland
Abstract
The purpose of this report is to review the literature on cancer among
persons employed in agriculture, to characterize the value of this line
of research, and to recommend future directions. Farmers, despite a generally
favorable mortality, appear to experience elevated rates for several cancers,
including leukemia, non-Hodgkin's lymphoma, multiple myeloma, soft-tissue
sarcoma, 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) appear to be increasing in the general
population. No set of established etiologic factors explains all the cancer
excesses observed among farmers, although several are associated with naturally
occurring or medically induced immunodeficiencies. This suggests that there
may be factors in the agricultural environment that introduce immune system
deficiencies. Farmers are exposed to a variety of substances that could
operate through this mechanism, including pesticides, engine exhausts, solvents,
dusts, and zoonotic microbes. Studies to further characterize the cancer
risk among farmers, their dependents, and farm laborers, and to identify
the exposures that may be involved would not only be useful in providing
a safe work environment in agriculture but may furnish considerable insight
into the causes for a number of tumors that are rising in incidence in the
general population. -- Environ Health Perspect 103(Suppl 8):00-00
(1995)
Key words: agriculture, farmers, farmworkers, cancer, pesticides,
review, exposures
This paper was presented at the President's Cancer Panel
Conference on Avoidable Causes of Cancer held 7-8 April 1994 in Bethesda,
Maryland. Manuscript received: 9 March 1995; manuscript accepted: 24 March
1995.
Address correspondence to Dr. Aaron Blair, National Cancer
Institute, Occupational Studies Section, Executive Plaza North, Room 418,
Rockville, MD 20892-7364. Telephone: (301) 496-9093. Fax: (301) 402-1819.
E-mail: Blaira@epndce.nci.nih.gov
Abbreviations used: DDT, dichlorodiphenyltrichloroethane;
DHHS, Department of Health and Human Services; NCI, National Cancer Institute.
Introduction
The agricultural population is large, with an estimated 2 million farmers,
2.7 million farm laborers, and perhaps 6 million family members (1).
Agriculture is an important component of the national economy, and the population
has some unique characteristics and exposures. Farm populations may come
into contact with a variety of potentially hazardous substances, including
pesticides, fertilizers, fuels and oils, engine exhausts, paints, solvents,
welding fumes, dusts, and zoonotic microbes. Epidemiologic studies of agricultural
populations are desirable because a) farmer owner/operators, farm
laborers, and dependents of farmers have not been as intensely studied as
many other occupational groups, and such research is necessary to ensure
a safe workplace, and b) many exposures traditionally associated
with farming are becoming more commonplace in the urban environment. Thus,
investigations among farmers may provide important clues to the etiology
of cancer in the general population. In this paper, we provide a brief overview
of cancer risks among farmers and suggest directions for future research.
Cancer Among Farmers
In the mid-1970s, the National Cancer Institute (NCI) developed a series
of maps displaying mortality patterns for specific cancers in the United
States by county or state economic area (2). The map for leukemia
showed a string of high-rate counties through the center of the United States,
ranging from the Dakotas to Texas. This pattern suggested a role for some
factors associated with agriculture because these high-rate areas generally
did not include cities. A series of research projects was initiated to clarify
cancer risks among farmers and to identify factors that might be involved.
Occupational surveys available from many developed countries were used to
evaluate the overall cancer pattern among farmers. These data indicate that
farmers have a more favorable experience than the general population for
many causes of death, including all causes combined, heart disease, all
cancers combined, as well as cancers of the lung, bladder, liver, colon,
esophagus, rectum, and kidney (3) (Table 1). Despite their overall
excellent mortality, farmers from many countries tend to experience higher
rates than the general population for cancers of the lymphatic and hematopoietic
system, skin (melanotic and nonmelanotic), soft-tissue sarcoma, lip, prostate,
brain, and stomach (3). Although the excesses for these cancers are
not large in absolute terms, they are striking because they occur in an
occupational group that has a low mortality for most other causes. A review
of cohort and case-control studies that provide information on cancer risk
among farmers noted a similar pattern to the general surveys; i.e., lower
risk from major causes of death and from many cancers than other groups
but higher risks for the cancers noted above (4).
Why are these particular cancers excessive among farmers? What ties them
together? Although there are no clear explanations, three findings stand
out. First, these tumors are not smoking related. In fact, the smoking-related
cancers tend to have lower rates among farmers than among other occupational
groups. This is consistent with the lower prevalence of smoking among farmers
than among the general population and many other occupational groups (5).
Second, several of the cancers that are excessive among farmers show rising
rates among the general population of many developed countries. These tumors
include multiple myeloma, non-Hodgkin's lymphoma, and cancers of the prostate,
brain, and skin (6). Finally, several of the cancers that are excessive
among farmers appear to be associated with genetic or therapeutically induced
immunodeficiencies (7-12). Tumors linked to immunodeficiencies include
non-Hodgkin's lymphoma, leukemia, melanoma, soft-tissue sarcoma, and cancers
of the stomach, brain, and lip.
The overlap of cancers occurring excessively among farmers, cancers showing
rising rates in the general population, and cancers occurring among individuals
with immunodeficiencies suggests that investigations of agricultural populations
may be useful to identify new factors involved in the etiology of cancer,
to help explain rising rates for some tumors, and to provide leads regarding
mechanisms of environmental carcinogens.
Although farmers may come into contact with a number of potentially hazardous
substances, epidemiologic studies have only recently attempted to focus
on specific exposures. Early investigations looked at farmers as a group
or at broad subgroups of farmers defined by agricultural commodities produced.
Because individuals with different farming operations can have quite diverse
exposures, this approach has a limited capability to identify specific factors
that may contribute to the cancer burden. More targeted investigations have
focused primarily on pesticides, but other agricultural exposures such as
fuels, oils, engine exhausts, organic solvents, dusts, and microbes need
study.
In epidemiologic investigations focusing on pesticides, the strongest
association has been between non-Hodgkin's lymphoma and phenoxyacetic acid
herbicides (13-16), but leukemia has been linked with several insecticides
(17), soft-tissue sarcoma with phenoxyacetic acid herbicides (18)
and animal insecticides (19), ovarian cancer with triazine herbicides
(20), prostate cancer with herbicides (21), and DDT with cancers
of the lung (22) and pancreas (23) (Table 2). Most studies
have included only men, but investigations including women have reported
associations between several pesticides and non-Hodgkin's lymphoma (24)
and multiple myeloma (25). Studies of women in the general population
have reported an association between DDT and breast cancer (26-28).
Investigations of this association among women in agriculture are needed
and some are under way. High-priority research efforts for the future include
a concentration on methodologic issues in exposure assessment as well as
etiologic concerns.
Exposure Assessment
The major limitation to date in investigations of cancer among agricultural
populations is the lack of detail regarding exposure. Often, no specific
exposure assessment is undertaken and analyses are based simply on the job
title farmer. This does not allow identification of specific factors that
may be related to the development of cancer and tends to introduce confusion
because disease risks are often compared between farmers with radically
different exposure patterns. Since different farming operations may yield
quite diverse exposures, simply comparing farmers overall, or broad subgroups
of farmers, introduces exposure misclassification, which decreases study
power and tends to bias risk estimates toward the null, thus diminishing
opportunities to identify etiologic factors. More detailed assessment of
exposures is needed in the future.
Assessment of historical exposures is always difficult in epidemiologic
studies. At first glance, it may appear that reconstructing agricultural
exposures would be particularly problematic. However, exposure assessment
in agriculture may be no more difficult to assess than many lifestyle or
other occupational factors. In fact, studies of farmers probably offer special
advantages, particularly when exposures are based on interview data. Farmers
are very knowledgeable about chemicals they use. In many industrial situations,
management makes decisions regarding the selection and purchase of materials,
while labor actually uses them. In such situations, neither management nor
labor is familiar with all aspects of the operation. On many family farms,
unlike in most industries, the farmer represents both labor and management
and is engaged in the selection, purchase, and use of farm chemicals. For
pesticides, the farm owner/operator decides if there is a pest problem,
determines when to treat the problem, selects the pesticide, applies the
chemical, checks the results of the treatment, and records the purchases
(this is a tax-deductible expense). These activities reinforce memory, which
enhances the reliability and validity of information obtained by interview.
There is also an impression that farmers use so many pesticides and change
chemicals so frequently that recall must be poor. This is not the case for
many farmers. In several NCI surveys, the total number of pesticides used
over a farmer's lifetime averaged less than 10 and, typically, the same
ones were used year after year (29). Thus, the number of chemicals
used seems amenable to recall. This is not to say, however, that improvements
in assessment of pesticide exposures are not needed.
It may be more difficult to reconstruct pesticide exposure histories
for agricultural workers who are not farm owner/operators. For example,
migrant and seasonal workers are unlikely to know which pesticides have
been applied to the fields where they work. It is clear that different approaches
must be developed to assess exposures in this group (30).
The experimental and epidemiologic evidence suggests that potentially
carcinogenic pesticides are not likely to be limited to any particular chemical
class (31). To date, too few epidemiologic investigations have attempted
to obtain information on individual pesticides. This must be the focus in
the future. Exposure assessment can be improved by collecting information
from several sources (e.g., interviews with farmers and suppliers), reviewing
records (farmers are now required to keep records of pesticide purchases),
conducting exposure monitoring during application, and obtaining blood or
urine specimens for assessment of dose. Interviews should probe for information
on specific pesticides and amounts used, mixing and application procedures,
and types of protective equipment and actions used.
No one particular exposure assessment approach is likely to be universally
successful in all situations. It may not be possible to achieve the desired
degree of quantification of exposure simply from interviews and records.
Environmental and biologic monitoring provides such quantification but only
for a very short period (usually days). Farming activities resulting in
exposures are often limited to relatively brief time periods during the
year; thus, when the monitoring occurs is critical. The use of detailed
questionnaires supplemented with monitoring and other information together
would allow a more accurate classification of relative exposure.
Pesticides understandably have been suspected of causing cancer in agricultural
populations because a number of these chemicals are carcinogenic in laboratory
bioassays. The mechanism of action of pesticides, however, is not well understood.
Although some pesticides have genotoxic effects (32), others may
cause immune system defects (33). For example, it has been proposed
that organophosphate insecticides may play a role in oncogenesis through
their inhibition of serine esterases, which are necessary for functioning
of T-lymphocytes and natural killer cells (34). Engine exhausts may
also affect the immune system because polycyclic aromatic hydrocarbons have
been associated with depression of serum IgG and IgA levels (35).
Stimulation of the immune system through exposure to mycotoxins also appears
worthy of study (36). Investigations of agricultural exposures that
incorporate biologic marker components are needed to characterize potential
environmental hazards faced by the agricultural and general population.
Efforts must also be undertaken to obtain information on exposure to
potential agricultural hazards other than pesticides. The epidemiologic
research to date has focused on pesticides, but it is time to pay attention
to engine exhausts, fuels and oils, dusts, fertilizers, and zoonotic viruses.
Efforts to better characterize exposures from drinking water are also needed,
as contamination of drinking water by agricultural fertilizers and pesticides
represents a growing problem in many areas of the country, particularly
in agricultural areas (37).
Epidemiologic Investigations
Most epidemiologic investigations to date have focused on farm owner/operators
and have mainly included men. Additional work on this population is warranted
because few studies so far have attempted to assess cancer risks from specific
agricultural exposures. Long-term prospective studies should be considered
in addition to case-control designs. Future efforts, however, must also
be expanded to include evaluation of cancer risks among other groups in
the agricultural setting; i.e., spouses, children, and laborers.
The role of spouses in the farming operation varies. Some wives are fully
engaged in all activities and may perform the same tasks as their husbands.
Investigation of cancer risks among this population is important to assess
risks for female-related tumors from agricultural exposures. A study of
women farmers is also important to determine whether cancer risks from agricultural
exposures vary by gender. Such differences could occur because of anatomical
and physiologic differences between the sexes (38) or because different
approaches to job tasks result in disparate exposures.
Some spouses do not actually engage in farm activities that require direct
contact with farm chemicals, but because they live on the farm (which is
like living at the factory in other industries), indirect exposure is possible.
For example, the potential for contamination of vehicles, furniture, and
clothing may provide exposure opportunities to pesticides used on the farm
to family members not directly engaged in application. This level of exposure,
although it may be considerably less than that of farm operators, may equal
or exceed exposure levels experienced by the general public. Studies of
farm spouses could provide valuable information regarding cancer risks to
the general population from such indirect exposures. Farm children may also
experience direct and indirect exposures at ages when they may be especially
susceptible.
Farm laborers such as seasonal and migrant workers may also experience
unique exposure scenarios that put them at special risk (30). Exposures
may occur at a young age because children work in the fields or must accompany
their parents to the fields because of the lack of child care facilities.
Lack of protective equipment and prompt access to showers and laundry facilities
(39) may exacerbate hazards by prolonging the time during which pesticides
are in contact with the skin.
There is growing concern over contamination of food and drinking water
with agricultural chemicals. Studies of agricultural populations may offer
special advantages to address this issue. For example, the level of contamination
of drinking water is greater in private wells than in public water systems,
and farms often use private wells as their water source. This, plus the
residential stability of farm families, offers distinct advantages over
urban areas for the study of cancer risks from chemical contamination of
drinking water.
It is important to remain alert for unusual exposure situations that
may provide unique opportunities to evaluate cancer risks from specific
agricultural chemicals. For example, studies of cancer risks among persons
engaged in fruit and vegetable production have not been conducted. The intense
use of pesticides, particularly fungicides, on these commodities underscores
the need for evaluation. Studies of workers in hothouses producing flowers
and vegetables could be informative because of heavy exposures from the
use of chemicals within a confined space. Special opportunities may exist
in other countries where pesticides are used more heavily and exposures
may be considerably higher than in the United States.
Conclusion
Studies of cancer risk among agricultural populations will improve health
and safety among this important segment of the population. These investigations
may also alert us to possible hazards to the general population, identify
factors contributing to the rising incidence of some cancers, and provide
clues to carcinogenic mechanisms.
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