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Agricultural Herbicide Use and Risk of Lymphoma and Soft-Tissue Sarcoma Shelia K

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Agricultural Herbicide Use and Risk of Lymphoma and Soft-Tissue Sarcoma Shelia K Agricultural Herbicide Use and Risk of Lymphoma and Soft-Tissue Sarcoma Shelia K. Hoar, ScD; Aaron Blair, PhD; Frederick F. Holmes, MD; Cathy D. Boysen; Robert J. Robel, PhD; Robert Hoover, MD; Joseph F. Fraumeni, Jr, MD A population-based case-control study of soft-tissue sarcoma (STS), Hodgkin's agents for leather and textiles, and disease (HD), and non-Hodgkin's lymphoma (NHL) in Kansas found farm medications.1 For these reasons, a pop¬ herbicide use to be associated with NHL (odds ratio [OR], 1.6; 95% confidence ulation-based case-control study was interval [CI], 0.9, 2.6). Relative risk of NHL increased significantly with number conducted to clarify whether agricul¬ of of herbicide and Men to herbicides tural use of herbicides and insecticides days exposure per year latency. exposed and NHL in than 20 had sixfold increased risk of NHL 95% affects risk of STS, HD, more days per year a (OR, 6.0; the United States. CI, 1.9, 19.5) relative to nonfarmers. Frequent users who mixed or applied the herbicides themselves had an OR of 8.0 (95% CI, 2.3, 27.9) for NHL. Excesses METHODS were associated with use of phenoxyacetic acid herbicides, specifically Kansas, a major wheat-producing acid. Neither STS nor HD was associated with 2,4-dichlorophenoxyacetic state, was chosen as the location for pesticide exposure. This study confirms the reports from Sweden and several the study, since herbicides have been US NHL states that is associated with farm herbicide use, especially used more frequently than other pesti¬ phenoxyacetic acids. It does not confirm the case-control studies or the cohort cides on wheat. 2,4-Dichlorophenoxy- studies of pesticide manufacturers and Vietnam veterans linking herbicides to acetic acid (2,4-D) has been the most STS or HD. commonly used herbicide in Kansas; (JAMA 1986;256:1141-1147) substantial amounts of 2,4,5-trichloro- phenoxyacetic acid (2,4,5-T) have also been used, along with myriad other EPIDEMIC-LOGIC studies from Swe¬ benzofurans. There have also been sev¬ chemicals.11 den have suggested that workers eral reports of increased STS and NHL exposed to phenoxyacetic acid herbi¬ among workers producing phenoxy¬ Cases cides and are at excess acetic acid herbicides4"7 and chlorophenols among All newly diagnosed cases of STS, risk of soft-tissue sarcoma farmers.8"10 (STS), HD, and NHL among white male Kan¬ and non- Hodgkin's disease (HD), sas 21 or For all residents, aged years older, Hodgkin's lymphoma (NHL).13 See also p 1176. from 1976 through 1982, were identi¬ three cancers, risks were increased fied through the University of Kansas fivefold to of wheth¬ sixfold, regardless Concern over possible carcinogenic (Kansas City) Cancer Data Service, a er exposures were contaminated by risks from phenoxyacetic acids and population-based registry covering the dibenzodioxins or di- polychlorinated chlorophenols is heightened by the state of Kansas. Cancer reporting, potential for widespread exposure. In mandated by Kansas law, is considered From the Epidemiology and Biostatistics Program, addition to herbicide formulations used complete, as evidenced by a higher National Cancer Institute, Bethesda, Md (Drs Hoar, Blair, in and in the Vietnam war, Hoover, and the Cancer Data Service, agriculture annual incidence rate for STS (4.1/ Fraumeni); occur in blue stain University of Kansas Medical Center, Kansas City (Dr these chemicals 100 000) than reported by the nearby Holmes and Ms Boysen); and the Division of Biology, retardants used in sawmills, slime con¬ Iowa National Cancer Institute-spon¬ Kansas State University, Manhattan (Dr Robel). trol preparations in paper and pulp sored Reprint requests to Epidemiology and Biostatistics Surveillance, Epidemiology, and Program, National Cancer Institute, Landow 4C16, manufacturing, cutting oils and fluids, End Results registry (3.4/100 000). Bethesda, MD 20892 (Dr Hoar). wood preservatives, waterproofing There were 200 men diagnosed with Downloaded from jama.ama-assn.org at University of Waterloo on January 13, 2012 Table 1.—Soft-Tissue Sarcoma, Hodgkin's Disease, and Non-Hodgkin's Lymphoma in Relation to Duration and Frequency of Herbicide Use Soft-Tissue Sarcoma Hodgkin's Disease Non-Hodgkin's Lymphoma Odds Ratio Odds Ratio Odds Ratio No. of No. of (95% Confi- No. of (95% Confi- No. of (95% Confi- Controls Cases dence Interval) Cases dence Interval) Cases dence Interval) Nonfarmers 286 38 1.0 50 1.0 37 1.0 Farmers 662 95 1.0 (0.7, 1.6) 71 0.8 (0.5, 1.2) 133 1.4 (0.9, 2.1) Duration of herbicide use, y 0 470 73 1.1 (0.7, 1.8) 43 0.7 (0.5, 1.2) 93 1.3 (0.8, 2.1) 1-5 53 0.7 (0.2, 2.0) 0.9 (0.4, 2.2) 9 1.3 (0.6, 3.1) 6-15 58 0.7 (0.2, 1.9) 0.8 (0.3, 1.9) 12 1.6 (0.7, 3.4) :16 57 11 1.4 (0.6, 3.1) 10 1.2 (0.5, 2.6) 16 2.0 (1.0, 4.0) Unknown 24 X for trend 0.13 0.11 2.06 P (one-tailed) .45 .46 .02 Frequency of herbicide use, d/y 0 497 74 1.1 (0.7, 1.7) 45 0.7 (0.4, 1.1) 94 1.3 (0.8, 2.0) 1-5 102 0.6 (0.3, 1.5) 16 1.0 (0.5, 1.9) 19 1.4 (0.7, 2.6) 6-10 29 0.5 (0.1, 2.3) 0.4 (0.1, 1.7) 1.6 (0.5, 4.3) 11-20 13 2.9 (0.8, 9.5) 1.3 (0.2, 6.8) 2.6 (0.8, 8.8) ;21 12 0.8 (0.04, 6.5) 1.0 (0.2, 4.1) 6.0 (1.9, 19.5) Unknown X for trend 0.002 -0.56 3.33 P (one-tailed) .50 .29 .0004 STS and 173 men with HD. A random 92.3% of the working residential tele¬ farm locations and sizes, herbicides sample of 200 men was drawn from the phone numbers called, a person an¬ and insecticides used, years and acres 297 men diagnosed with NHL from swered who was willing to provide the treated, names and locations of compa¬ 1979 through 1981. names and ages of household members nies where pesticides were purchased, Pathology specimens for 87% of the aged 21 to 64 years and, if someone in method of application, days per year cases were reviewed by a panel of three the household was selected as a control, exposed, and use of protective equip¬ pathologists to confirm the diagnoses the household address. For deceased ment. Information on other crops was and to standardize the subgroup termi¬ patients, the controls were selected not obtained; however, in 1978, these nology.12,13 Specimens for the remaining from Kansas state mortality files, with four crops constituted 94% of Kansas cases either could not be obtained the additional matching factor of year farm acreage and 87% of acres treated (11%) or were of poor or insufficient of death. Persons with a cause of death with herbicides.1116 All but four sub¬ quantity to allow review (2%). For of STS, HD, NHL, a malignancy of an jects who lived or worked on farmland STS, HD, and NHL cases, the confir¬ ill-defined site (International Classifi¬ as adults grew at least one of the four mation rates were 81%, 85%, and 90%, cation of Diseases code 195), homicide, specified crops. respectively. Among the eligible histo- or suicide were excluded. One half of Interviews were obtained from 133 logically confirmed cases, 139 were the patients with STS and NHL died patients with STS, 121 with HD, 170 STS, 132 HD, and 172 NHL. before the initiation of the study, while with NHL, and 948 controls, which only one third of the patients with HD represented 95% of the eligible sub¬ Controls had died. The next of kin were inter¬ jects (patients, 96%; controls, 94%). The controls were white men from viewed for deceased subjects. The same The overall response rate, a weighted the general population of Kansas. controls were used for comparisons average accounting for the initial Three controls (N=1005) were matched with the three different cancer series refusals in the random digit-dialing to each patient on age ( ± 2 years) and when of comparable age. control selection process, was 93%. vital status. For living patients, con¬ trols aged 65 years or older were Interview selected from the Health Care Financ¬ The patients and controls, or their Pesticide Suppliers' Survey ing Administration file (Medicare), next of kin, were interviewed by tele¬ To evaluate potential observation whereas controls aged 64 years or phone between December 1982 and bias, corroborative evidence of the self- younger were selected by telephone, January 1984. The questions on farm¬ reported pesticide exposures was using a two-staged random digit-dial¬ ing practices covered the calendar sought for a sample of 130 subjects ing technique.14 Control selection was years working or living on farmland with farming experience. Suppliers for not biased by differences in telephone during which any of four specific crops 110 subjects were located and provided coverage for urban (91%) and rural (wheat, corn, sorghum, or pasture) information on the subject's crops and (90% ) white Kansan households.15 For were grown or livestock was raised, the herbicide and insecticide purchases. Downloaded from jama.ama-assn.org at University of Waterloo on January 13, 2012 in Relation Herbicide Table 2.—Non-Hodgkin's Lymphoma to Group risk of STS or HD were seen with either duration or of herbi¬ No.
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