Cancer Epidemiology Biomarkers & Prevention Vol. 14, 2446-2448, October 2005
© 2005 American Association for Cancer Research
Positive Association of Farm or Rural Residence with Acute Myeloid Leukemia Incidence in a Cohort of Older Women
Penny J. Sinner1,
James R. Cerhan4,
Aaron R. Folsom1 and
Julie A. Ross2,3
1 Division of Epidemiology and Community Health, School of Public Health, and 2 Department of Pediatrics, University of Minnesota; 3 University of Minnesota Cancer Center, Minneapolis, Minnesota; and 4 Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota
Requests for reprints: Julie A. Ross, University of Minnesota Cancer Center, MMC 422, 420 Delaware Street Southeast, Minneapolis, MN 55455. Phone: 612-626-2902; Fax: 612-626-4842. E-mail: ross{at}epi.umn.edu
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Abstract
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The etiology of acute myeloid leukemia (AML) is relatively unknown. Incidence rates are highest in the agricultural Midwest region compared with other regions of the United States. Many studies have examined the relationship between farming and leukemia, but most have mainly focused on men. We examined the potential association between farm or rural residence and AML in the Iowa Women's Health Study. In 1986, 37,693 women who were free of prior cancer completed a lifestyle and health questionnaire, which included a question on the place of residence. Women were subsequently followed until 2002 for cancer incidence; 79 women developed AML during the time period. Women who lived on a farm at baseline were more likely (relative risk, 1.91; 95% confidence interval, 1.19-3.05) to develop AML compared with women who did not live on a farm. Further, women who reported living on a farm or in a rural area were twice as likely (relative risk, 2.38; 95% confidence interval, 1.33-4.26) to develop AML compared with women who lived in a city with a population of >10,000 people. These results provide evidence that women who live on farms or rural areas are at an increased risk of AML.
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Introduction
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Acute myeloid leukemia (AML) is the most common type of leukemia in adults, and the incidence increases with age (1). For adults under the age of 65 years, the incidence rate is 1.6/100,000, whereas for adults over the age of 65 years, the incidence rate is 13.7/100,000 (1). Survival rates are generally poor, particularly for those over the age of 65 years; 5-year survival rates in the elderly are about 3.8% (1).
There are few established risk factors for AML. Benzene, radiation, prior chemotherapy treatments for cancer, and cigarette smoking have been causally linked with AML (2). Recent studies have reported a positive association between obesity and adult AML (3-6). Other risk factors that have been inconsistently associated with AML include alcohol use, hair dyes, and living near nuclear plants (2).
Compared with other parts of the United States, the incidence rates of leukemia are highest in the Midwest (1). It has been hypothesized that farming and its related exposures (e.g., pesticides) may account for the increased risk (7, 8). A number of studies, focused primarily on men, have reported positive associations between farming and leukemia, whereas other studies have shown no elevated risk (2). Only two small studies have examined the association between farming and AML: one reported no association (9) whereas the other reported a positive association (10). To study the association between farm/rural residence and risk of AML in women, we examined the potential association between farm/rural residence and risk of AML using the Iowa Women's Health Study, a large prospective cohort study of health in older women.
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Materials and Methods
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The methods of the Iowa Women's Health Study have been published in detail elsewhere (11, 12). Briefly, in 1986, questionnaires were mailed to nearly 100,000 women, ages 55 to 69 years, who were randomly selected from Iowa 1985 driver's license records; 41,836 (42%) of the women returned the questionnaire and were subsequently followed for mortality and cancer incidence. Nonresponders were slightly less likely to live in rural counties, were on average 3 months younger, and were 0.4 kg/m2 heavier than responders (13).
On the baseline questionnaire, participants were asked the location of their residence and chose from the following responses: on a farm; rural area but not a farm; city or town of population under 1,000; city or town of population 1,000 to 2,499; city or town of population 2,500 to 10,000; or city or town of population over 10,000. For this analysis, additional information evaluated included age, education level, marital status, weight and height, smoking status, duration of smoking, daily alcohol consumption, whether or not the participant had been diagnosed with diabetes or had received a blood transfusion. Women were also asked if they participated in any leisure exercise and, if so, how often they participated in moderate and vigorous activities. These questions were combined to create a physical activity score (low, medium, or high).
Cancer incidence between 1986 and 2002 was obtained through computer linkage with the Iowa Cancer Registry, which is part of the Surveillance Epidemiology and End Results program. Topographic and morphologic data from the International Classification of Diseases for Oncology, Third Edition (14), were used to classify incident AML and included the following codes: 9840, 9861, 9866, 9871, 9872, 9873, 9874, 9891, 9895, 9896, 9897, 9910, and 9920.
Women who, at baseline, reported having cancer other than nonmelanoma skin cancer were excluded (n = 3,830) along with women who were missing place of residence variables (n = 313). After these exclusions, 37,693 women were included in this analysis, including 79 who developed AML through December 31, 2002.
Personal characteristics at baseline were compared for women who lived on a farm and those who did not using the Pearson's 
2 test for categorical variables and the t test for continuous variables. Age-adjusted hazard ratios and 95% confidence intervals (95% CI) were computed using Cox proportional hazards regression with the SAS procedure PHREG (15). Variables considered for potential confounding are those displayed in Table 1. None of these variables met the confounding criteria of a 10% change in parameter estimates when comparing the adjusted model to the crude model. Age-adjusted only models are provided given that the incidence of AML increases with age.
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Results
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Compared with women not living on a farm, women living on a farm were less likely to smoke, and those that did smoked for fewer years. They were also less likely to drink alcohol. Lastly, women living on a farm were more likely to be married and were more likely to be overweight and obese than women not living on a farm (Table 1). Whereas there were statistically significant differences between women living on a farm compared with those not living on a farm for other characteristics, we chose to disregard the significance due to minimal differences and a large sample size.
Compared with women who did not develop AML, women who developed AML were more likely to live on a farm or in a rural area (Table 2), were more likely to be obese, and were more likely to have a low physical activity level (results not shown). AML incidence was unrelated to age, education, marital status, smoking, pack-years of smoking, blood transfusion, alcohol consumption, or diabetes.
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Table 2. Rates of AML incidence (per 100,000 person-years) according to various baseline characteristics, The Iowa Women's Health Study, 1986-2002
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After adjusting for age, women who lived on a farm were significantly more likely (hazard ratio, 1.91; 95% CI, 1.19-3.05) to develop AML compared with women who did not live on a farm (Table 3). Further, women who reported living on a farm or in a rural area were twice as likely (hazard ratio, 2.38; 95% CI, 1.33-4.26) to develop AML compared with women who lived in a city with a population of >10,000 people.
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Table 3. Age-adjusted hazard ratios and 95% CIs for incident AML in relation to place of residence, The Iowa Women's Health Study, 1986-2002
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Discussion
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Women living on a farm were 1.91 times as likely to develop AML compared with women who did not live on a farm, and women living on a farm or in a rural area were 2.38 times as likely to develop AML compared with women who lived in city with a population of >10,000 people.
Very few studies have examined the association between farming and leukemia in women and, to our knowledge, no studies have looked at farming and AML specifically in women. Three incidence studies (16-18) and one mortality study (19) have examined the relationship between farming and leukemia for both men and women; one of which examined the relationship between farming and AML in men and women (16). Of these four studies, only two have examined the relationship between farming and leukemia for the sexes separately (18, 19).
Blair et al. (19) examined death certificates for those that listed farming as the usual occupation in 23 states between 1984 and 1988 to determine cause of death. Twenty-four female and 1,072 male farmers died of leukemia during that time period. Leukemia deaths among these farmers were 77% higher than expected in the central region of the United States for female farmers and were higher in all regions of the United States (except the west) for male farmers based on mortality data among the nonfarming populations in those regions (19).
A study by Ronco et al. (18) examined cancer risk for farmers in Denmark and Italy. A cohort of Danish farmers was identified from the 1970 census for a 10-year follow-up study of cancer incidence and a cohort of Italian farmers was identified from the 1981 census and followed for 6 months. Thirty-eight female farmers from Denmark and nine female farmers from Italy developed leukemia. In the Danish cohort, leukemia incidence was 122% higher than expected for women that were self-employed on farms compared with women without a farming occupation, but leukemia incidence for females that were employed by other farm owners or by women that helped on the family farm was not higher than expected. Female Italian farmers that were self-employed or employed by others did not have an excess incidence of leukemia. Ronco et al. also reported that self-employed male farmers and male farmers employed by others did not have an excess of leukemia incidence in either Italy or Denmark (18).
In a case-control study on farming and risk of leukemia, Linos et al. (17) compared 138 cases of leukemia that occurred between 1955 and 1974 and 274 controls from Olmsted County. Medical charts were reviewed to verify diagnoses and determine occupation. A higher percentage of cases (5.1%) were living on a farm than controls (1.8%). This difference was not statistically significant (17). There was also no significant association between farming and AML when comparing those that lived or worked on a farm and those that did not (17).
Lastly, Richardson et al. (16) completed the only study that looked at farming practices and AML specifically. One hundred eighty-five cases and 513 hospital-based matched controls were examined for farming-related exposures and incidence of AML. Exposure to pesticides slightly increased the risk of AML, although it was not significant (relative risk, 1.38; 95% CI, 0.73-2.62). They also reported that exposure to weed killers increased the risk of AML, but again the association was not statistically significant (odds ratio, 3.15; 95% CI, 0.92-10.8; ref. 16).
There are some limitations to the study that need to be discussed. We had no information about exposures connected with farms. We also did not consider occupation in our analysis, and many women living on a farm may not be exposed to farming-related hazards. Further, we had no information about the duration of time lived at the current residence. Nevertheless, there were several strengths of our study. We were able to examine the association between farming and AML using a large prospective cohort study of older women and we were able to use incidence rather than mortality data. We also were able to look at AML separately, instead of all types of leukemia, which have clear etiologic differences. These data provide some evidence for an association between farm residence and AML incidence for older women.
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Footnotes
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Grant support: National Cancer Institute, U.S. Department of Health and Human Services grants R01 CA39742 and R01 CA107143.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 5/23/05;
revised 7/29/05;
accepted 8/11/05.
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Abstract
Introduction
