Search

Background: An increased rate of non-Hodgkin's lymphoma (NHL) has been repeatedly observed among farmers, but identification of specific exposures that explain this observation has proven difficult., Methods: During the 1980s, the National Cancer Institute conducted three case-control studies of NHL in the midwestern United States. These pooled data were used to examine pesticide exposures in farming as risk factors for NHL in men. The large sample size (n = 3417) allowed analysis of 47 pesticides simultaneously, controlling for potential confounding by other pesticides in the model, and adjusting the estimates based on a prespecified variance to make them more stable., Results: Reported use of several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate. A subanalysis of these "potentially carcinogenic" pesticides suggested a positive trend of risk with exposure to increasing numbers., Conclusion: Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios.

Objective: Data from three population-based case-control studies conducted in Kansas, Nebraska, Iowa, and Minnesota were pooled to evaluate the relationship between the use of organophosphate pesticides and non-Hodgkin's lymphoma (NHL) among white male farmers., Methods: The data set included 748 cases of non-Hodgkin's lymphoma and 2236 population-based controls. Telephone or in-person interviews were utilized to obtain information on the use of pesticides. Odds ratios (OR) adjusted for age, state of residence, and respondent status, as well as other pesticide use where appropriate, were estimated by logistic regression., Results: Use of organophosphate pesticides was associated with a statistically significant 50% increased risk of NHL, but direct interviews showed a significantly lower risk (OR = 1.2) than proxy interviews (OR = 3.0). Among direct interviews the risk of small lymphocytic lymphoma increased with diazinon use (OR = 2.8), after adjustment for other pesticide exposures., Conclusions: Although we found associations between the risk of NHL and several groupings and specific organophosphate pesticides, larger risks from proxy respondents complicate interpretation. Associations, however, between reported use of diazinon and NHL, particularly diffuse and small lymphocytic lymphoma, among subjects providing direct interviews are not easily discounted.

Recent epidemiological studies have suggested an increased risk of non-Hodgkin lymphoma (NHL) from carbamate insecticide use among farmers. To further explore the possible relationships, we conducted a pooled analysis of three population-based case-control studies conducted in four midwestern states in the United States. A total of 985 white male subjects and 2895 control subjects were included in this analysis. Unconditional logistic regression was used to estimate the association and control for confounding. Compared with nonfarmers, farmers who had ever used carbamate pesticides had a 30% to 50% increased risk of NHL, whereas farmers without carbamate pesticide use showed no increased risk. Analyses for individual carbamate pesticides found a more consistent association with Sevin but not carbofuran, butylate, or S-ethyl dipropylthiocarbamate plus protectant. Among farmers using Sevin, the risk of NHL was limited to those who personally handled the product, those who first used the product for > or = 20 years before their disease diagnosis, and those who used the product for a longer period. These associations persisted after adjusting for other major classes of pesticides. These results suggest an increased risk of NHL associated with carbamate pesticide use, particularly Sevin. Further investigation of the association is warranted.

Objectives: The objective of this pooled analysis was to examine whether exposure to DDT was associated with the risk of non-Hodgkin's lymphoma among male farmers., Methods: Data from three case-control studies from four midwestern states in the United States (Nebraska, Iowa, Minnesota, Kansas) were pooled to carry out analyses of 993 cases and 2918 controls. Information on use of agricultural pesticides and other risk factors was based on interviews. Non-farmers (people who had never lived or worked on a farm) were used as a reference category., Results: There were 161 cases and 340 controls who reported use of DDT on animals or crops, or on both, yielding an odds ratio (OR) of 1.2 (95% confidence intervals (95% CI) 1.0 to 1.6). Farmers who had used DDT for > or = 15 years had an OR of 1.5 (95% CI 1.0 to 2.3). Adjustment for respondent status and use of other pesticides resulted in slightly reduced ORs. Analyses by the number of days of use a year was limited to the Nebraska data. The most notable increase was found among farmers who used DDT for > or = 5 days a year (OR 2.6, 95% CI 1.1 to 5.9); however, additional adjustment for use of organophosphates, phenoxyacetic acids, and the individual pesticides lindane, malathion, and atrazine reduced the ORs to 1.0, 0.9, 1.1, 1.6, and 1.9 respectively., Conclusions: No strong consistent evidence was found for an association between exposure to DDT and risk of non-Hodgkin's lymphoma. It seems that the excess risk initially found may be explained by use of other pesticides.

To investigate factors associated with pesticide-related visits to health care providers (i.e., doctor or hospital visits), responses to self-administered questionnaires received from 35,879 licensed restricted-use pesticide applicators participating in the Agricultural Health Study were analyzed. (In Iowa, applicators are actually certified, whereas in North Carolina they are licensed; for ease of reference, the term license will be used for both states in this paper.) The cohort reported a total of more than 10.9 million pesticide-application days. These applications were associated with one or more pesticide-related health care visits by 2,214 applicators (7.0% of the applicator cohort for whom health care visit data were available). The odds of a pesticide-related health care visit were increased for commercial applicators compared to private applicators [odds ratio (OR = 1.77; 95% confidence interval (CI), 1.52-2.06) and for applicators who used insecticides 70 times or more in their lifetime compared to those who used insecticides less frequently (OR = 1.43; CI, 1.26-1.63). After adjusting for the number of applications in a logistic regression model, significantly higher odds of health care visits were observed among North Carolina applicators compared to Iowa applicators (OR = 1.35; CI, 1.17-1.52), among applicators who mixed their own pesticides (OR = 1.65; CI, 1. 22-2.23), and among applicators who personally repaired their pesticide application equipment at least once per year (OR = 1.12; CI, 1.06-1.25). Significantly lower odds were found among female versus male applicators (OR = 0.68; CI, 0.46-0.99) and among applicators who graduated from high school versus those who did not (OR = 0.82; CI, 0.71-0.94 for high school graduates and OR = 0.79; CI, 0.68-0.91 for those with at least some college). Several methods of pesticide application to crops, seed, or stored grain were also associated with significantly elevated odds ratios of health care visits. These observations suggest that several steps can be taken to reduce the number of health care visits resulting from occupational exposure to pesticides. The implications of this pattern of pesticide-related health care visits may have etiologic implications for cancer and other chronic diseases.

Data from population-based case-control studies of non-Hodgkin's lymphoma among white men from Kansas, Nebraska, Iowa, and Minnesota were pooled to evaluate potential risks from environmental exposures in more detail, while controlling for potential confounding factors. These data provided the opportunity to evaluate the risk of non-Hodgkin's lymphoma from potential exposures to lindane, a pesticide that causes cancer in laboratory animals and has been associated with human cancer in a few epidemiologic investigations. This pooled data set includes 987 individuals with non-Hodgkin's lymphoma and 2,895 population-based controls. Information was obtained by telephone or in person interviews, which included detailed questions on farm practices and agricultural use of chemicals. Logistic regression was used to calculate odds ratios (ORs) adjusted for age, state of residence, and subject or proxy interviews. Reported use of lindane significantly increased the risk of non-Hodgkin's's lymphoma by 50%. Some use characteristics were suggestive of an association. ORs were greater among persons who first used the pesticide 20 years before diagnosis (OR = 1.7) than more recently (OR = 1.3), among those who reported more frequent use (OR = 2.0 for use 5 or more days per year versus 1.6 for fewer than five days per year), and from use on crops (OR = 1.9), rather than from use on animals (OR = 1.3), although these differences were not statistically significant. On the other hand, ORs were lower when based on direct interviews (OR = 1.3) than on data from proxy respondents (OR = 2.1) and adjustment for potential confounding by use of 2,4-D and diazinon reduced the ORs associated with lindane use from 1.5 to 1.2 and 1.3, respectively. Lindane does not appear to be a major etiologic factor in the development of non-Hodgkin's's lymphoma, although a small role cannot be ruled out.

In response to reports linking non-Hodgkin's lymphoma (NHL) and the herbicide 2,4-dichlorophenoxyacetic acid, a retrospective cohort mortality study of 32,600 employees of a lawn care company was conducted. The cohort was generally young with short-duration employment and follow-up. In comparison to the US population, the cohort had significantly decreased mortality from all causes of death combined (307 deaths), arteriosclerotic heart disease, and accidents. There were 45 cancer deaths (59.6 expected, standardized mortality ratio [SMR] = 0.76, 95% confidence interval [CI] = 0.55, 1.01). Bladder cancer mortality was significantly increased, but two of the three observed deaths had no direct occupational contact with pesticides. There were four deaths due to NHL (SMR = 1.14, CI = 0.31, 2.91); three were male lawn applicators (SMR = 1.63, CI = 0.33, 4.77), with two of the applicators employed for three or more years (SMR = 7.11, CI = 1.78, 28.42). No other cause of death was significantly elevated among lawn applicators as a group or among those employed for three or more years. Although based on very small numbers and perhaps due to chance, the NHL excess is consistent with several earlier studies.

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.

There are an estimated three million hired migrant and seasonal farmworkers in the United States. Adults and children may be exposed to mutagenic and potentially carcinogenic pesticides during planting, weeding, thinning, and harvesting crops. Field conditions that provide little opportunity to wash skin or clothing to minimize pesticide absorption may intensify exposure. Little is known, however, about the occurrence of cancer in migrant or seasonal farmworkers. Most cancer epidemiologic research on agricultural populations has focussed on farm owner/operators. The few studies that have evaluated cancer in farmworkers suggest that, like farm owner/operators, they may be experiencing excesses of multiple myeloma and cancers of the stomach, prostate, and testis. A few studies suggest that the farmworkers may differ from farmers by experiencing excesses of cancers of the buccal cavity and pharynx, lung, and liver. Cervical cancer was elevated in female farmworkers in one study. Descriptive data and etiologic research on cancer among farmworkers and family members are urgently needed. Feasibility evaluations, however, should precede etiologic investigations because of possible difficulties in studying this population of workers. Issues that need to be evaluated include assessing where and when farmworkers and family members are diagnosed and/or treated for malignancies, the ability of farmworkers to provide histories of crops, locations, and years worked and living conditions, the ability of agricultural experts to determine likely pesticide exposures based on such farmworkers' histories, the ability to obtain information on potential confounding factors, the ability to recontact or determine vital status of specific farmworkers over time, the suitability of conducting studies in home-base vs. upstream counties, and the ability to study agriculturally related malignancies in persons who have left farm work before the disease occurs.

Non-Hodgkin's lymphoma has been found to be associated with agricultural pesticide use in men, but little is known about the risk in women. In a recent population-based, case-control study conducted in eastern Nebraska, no increased risk of non-Hodgkin's lymphoma was found in women who had ever lived or worked on a farm (odds ratio [OR] = 1.0). Neither the use of insecticides (OR = 0.8) nor herbicides (OR = 0.7) on the farm was associated with non-Hodgkin's lymphoma; however, the number of women who mixed or applied pesticides was small, particularly in comparison to men on farms. Small nonsignificant associations were observed among the women who personally handled insecticides (OR = 1.3) or herbicides (OR = 1.2). Women who personally handled organophosphate insecticides had a significant 4.5-fold increased risk of non-Hodgkin's lymphoma. Use of chlorinated hydrocarbon insecticides was associated with an OR of 1.6; however, the use on dairy cattle was associated with a 3-fold increased risk. Pesticide-related risks were greater among women with a family history of cancer, particularly a history of lymphatic or hematopoietic cancer among first-degree relatives.

Atrazine is the most commonly used herbicide in the United States and is a wide-spread groundwater contaminant in the Midwest. The role of atrazine in the development of human non-Hodgkin's lymphoma (NHL) was investigated in three case-referent studies conducted in four midwestern states in the United States. A total of 993 white men with NHL and 2918 population-based referents were interviewed concerning their agricultural practices. When the results of the three studies were combined, atrazine use was associated with an odds ratio of 1.4 [95% confidence interval (95% CI) 1.1-1.8, 130 cases, 249 referents) for NHL. However, adjustments for the use of 2,4-dichlorophenoxyacetic acid and organophosphate insecticides reduced the apparent association between NHL and atrazine in all but one state and reduced the associations for the long-term and frequent users in Nebraska. Detailed analyses suggested that there was little or no increase in the risk of NHL attributable to the agricultural use of atrazine.

Epidemiologic studies of farmers have linked pesticides with certain cancers. Information on exposures from many of these studies was obtained by interview of farmers or their next-of-kin. The reliability and validity of data on pesticide use obtained by recall, often years after the event, have been questioned. Pesticide use, however, is an integral component in most agricultural operations, and the farmers' knowledge and recall of chemicals used may be better than for many other occupations. Contrary to general belief, many farmers typically use only a few pesticides during their lifetimes and make only a few applications per year. Data from U.S. Department of Agriculture surveys indicate that herbicides are applied to wheat, corn, soybeans, and cotton and that application of insecticides to corn averages two or fewer times per year. In epidemiologic studies at the National Cancer Institute, the proportion of farmers ever reporting lifetime use of five or more different chemicals was 7% for insecticides and 20% for herbicides. Surrogate respondents have often been used in epidemiologic studies of cancer; they are able to recall pesticide use with less detail than the farmers themselves. The pesticides reported by surrogates were the same as reported by subjects themselves, but with less frequency. Comparison of reporting by cases and controls provided no evidence of case-response (differential) bias; thus, inaccurate recall of pesticide use by subjects or surrogates would tend to diminish risk estimates and dilute exposure-response gradients.

The incidence of non-Hodgkin's lymphoma (NHL) has increased over 50% in the last 15 years. This paper reviews the possible role of pesticides in this increase. While small increases in risk of NHL among farmers have been observed in general occupational surveys, recent studies focusing on specific pesticides have observed much larger risks. Frequent use of phenoxyacetic acid herbicides, in particular, 2,4-dichlorophenoxyacetic acid, has been associated with 2- to 8-fold increases of NHL in studies conducted in Sweden, Kansas, Nebraska, Canada, and elsewhere. Canine malignant lymphoma has also been associated with dog owner use of 2,4-dichlorophenoxyacetic acid and commercial lawn pesticide treatments. There are much fewer data linking NHL to other types of pesticides, but triazine herbicides, organophosphate insecticides, fungicides, and fumigants have also been associated with increased risk of NHL. Pesticide exposures are not limited to agricultural populations but are widespread in the general population through use on lawns, golf courses, rights-of-way, and elsewhere. Since the use of pesticides, particularly phenoxy herbicides, has increased dramatically preceding and during the time period in which the incidence of NHL has increased, they could have contributed to the rising incidence of NHL.

This article summarizes cancer risks among farmers to clarify the magnitude of the problem and to suggest directions for future research. Significant excesses occurred for Hodgkin's disease, multiple myeloma, leukemia, skin melanomas, and cancers of the lip, stomach, and prostate. Nonsignificant increases in risk were also noted for non-Hodgkin's lymphoma and cancers of connective tissue and brain. These excesses occurred against a background of substantial deficits among farmers for total mortality and mortality from many specific diseases. The tumors vary in frequency, histology, and prognosis and do not fall into any obvious grouping. Two commonalities may be important. Several of the tumors excessive among farmers appear to be rising in the general population and are excessive among patients with naturally occurring or medically induced immunodeficiencies. Therefore epidemiologic studies on specific exposures among farmers may help explain the rising trend of certain cancers in developed countries and provide clues to mechanisms of action for environmental carcinogens.

To evaluate the role of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in the development of non-Hodgkin's lymphoma (NHL), we conducted a population-based, case-control study in 66 counties in eastern Nebraska. Telephone interviews were conducted with 201 white men diagnosed with NHL between July 1, 1983, and June 30, 1986, and with 725 controls. There was a 50% excess of NHL among men who mixed or applied 2,4-D (odds ratio [OR] = 1.5; 95% confidence interval = 0.9, 2.5). The risk of NHL increased with the average frequency of use to over threefold for those exposed 20 or more days per year (p for trend = 0.051). Adjusting for use of organophosphate insecticides lowered the risk estimate for frequent users (OR = 1.8), but adjustment for fungicide use increased the risk estimate (OR = 4.5). Simultaneous adjustment for organophosphates and fungicides yielded an OR of 3.1 for farmers who mixed or applied 2,4-D more than 20 days per year. Risk also increased with degree of exposure, as indicated by application method and time spent in contaminated clothing, but not with the number of years of 2,4-D use or failure to use protective equipment. Although other pesticides, especially organophosphate insecticides, may be related to NHL, the risk associated with 2,4-D does not appear to be explained completely by these other exposures.

A population-based case-referent study in Kansas examined the relationship between exposure to insecticides and the development of soft-tissue sarcoma (STS) and Hodgkin's disease (HD). Data from telephone interviews for 133 STS cases, 121 HD cases, and 948 referents indicated that STS was associated with use of insecticides on animals, but not on crops. HD was not significantly associated with either use. STS risk was higher among the farmers who themselves mixed or applied insecticides to animals than among farmers who did not. Farmers who failed to use any protective equipment to reduce insecticide exposure were at a significantly elevated risk of STS. Risk rose with early calendar year of first use. The excess risk appeared to be primarily among fibrous and myomatous sarcomas with little association seen for lipomatous or other STS neoplasms. Myomatous sarcomas increased significantly with duration and time since first use of insecticides on animals. If the reported association between STS and insecticides is causal, the data suggest that exposure to the agent(s) responsible may have been reduced in the mid-1950s or the agent(s) have an average latency period for STS of at least 20 years.