Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phenoxy herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is widely used to control the growth of weeds and broadleaf plants. We convened a panel of 13 scientists to weigh the evidence on the human carcinogenicity of 2,4-D. The panel based its findings on a review of the toxicological and epidemiological literature on 2,4-D and related phenoxy herbicides. The toxicological data do not provide a strong basis for predicting that 2,4-D is a human carcinogen. Although a cause-effect relationship is far from being established, the epidemiological evidence for an association between exposure to 2,4-D and non-Hodgkin's lymphoma is suggestive and requires further investigation. There is little evidence of an association between use of 2,4-D and soft-tissue sarcoma or Hodgkin's disease, and no evidence of an association between 2,4-D use and any other form of cancer. Scientists on the panel were asked to categorize 2,4-D as a "known," "probable," "possible," or "unlikely" carcinogen or as a noncarcinogen in humans. The predominant opinion among the panel members was that the weight of the evidence indicates that it is possible that exposure to 2,4-D can cause cancer in humans, although not all of the panelists believed the possibility was equally likely: one thought the possibility was strong, leaning toward probable, and five thought the possibility was remote, leaning toward unlikely. Two panelists believed it unlikely that 2,4-D can cause cancer in humans.
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PMID:Weight of the evidence on the human carcinogenicity of 2,4-D. 182 Feb 67

The phenoxyacetic acid herbicides and the chlorophenols are compounds of economic importance. The herbicide 2,4-D is widely used in agriculture, industry, and the home. Recently, concern has arisen over their safety as a result of studies linking these compounds with soft-tissue sarcomas and non-Hodgkin's lymphomas. We reviewed the available literature in order to advise a provincial government regulatory body and investigated methodologic issues by examining the pattern of reported cases in Alberta. We conclude that, taking into account the serious limitations on methodology in the available data, the evidence for a causal association is strongest for non-Hodgkin's lymphomas and probably reflects either a weak effect or, possibly, a confounding exposure associated with the use of 2,4-D. Given the worst-case assumptions, however, the potency of 2,4-D as a carcinogen is probably weak. Its intrinsic toxicity is less than that of alternative herbicides and the hazard posed by its use is probably much less than either the use of chemical alternatives or manual cleaning of vegetation, which carry a high risk of occupational injuries.
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PMID:Phenoxyacetic acid herbicides and chlorophenols and the etiology of lymphoma and soft-tissue neoplasms. 248 16

An 18-year follow-up for mortality and cancer morbidity was conducted in a cohort of 1,909 men who had started spraying chlorophenoxy herbicides (mixture of 2,4-dichlorophenoxyacetic acid [2,4-D] and 2,4,5-trichlorophenoxyacetic acid [2,4,5-T]) in 1955 through 1971. In all, 384 persons had died during the follow-up, and there was a slight deficit in natural deaths (standardized mortality ratio [SMR] 0.84; 95% confidence interval [CI] 0.75-0.94). By contrast, there was a small, nonsignificant increase in accidental and violent deaths. The overall cancer mortality was slightly less than in the general population (SMR 0.83; 95% CI 0.65-1.02), and not a single case of death of non-Hodgkin's lymphomas (NHL) or soft tissue sarcomas (STS) was detected. With regard to cancer morbidity, the incident cases showed a slight deficit compared to the population figure (standardized incidence ratio [SIR] 0.81; 95% CI 0.67-0.97). One case of NHL was found (2.4 expected with 10 years of latency), but not a single case of STS (0.8 expected with 10 years of latency). While our study does not support the contention that spraying of 2,4-D and 2,4,5-T containing herbicides carries any significant risk of cancer, the medium to low statistical power of the study does not allow any far reaching negative conclusions regarding the carcinogenicity of the agents.
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PMID:Mortality and cancer morbidity of Finnish chlorophenoxy herbicide applicators: an 18-year prospective follow-up. 780 54

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.
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PMID:Non-hodgkin's lymphoma and agricultural use of the insecticide lindane. 940 31

Our objective in the study was to investigate the putative associations of specific pesticides with non-Hodgkin's Lymphoma [NHL; International Classification of Diseases, version 9 (ICD-9) 200, 202]. We conducted a Canadian multicenter population-based incident, case (n = 517)-control (n = 1506) study among men in a diversity of occupations using an initial postal questionnaire followed by a telephone interview for those reporting pesticide exposure of 10 h/year or more, and a 15% random sample of the remainder. Adjusted odds ratios (ORs) were computed using conditional logistic regression stratified by the matching variables of age and province of residence, and subsequently adjusted for statistically significant medical variables (history of measles, mumps, cancer, allergy desensitization treatment, and a positive history of cancer in first-degree relatives). We found that among major chemical classes of herbicides, the risk of NHL was statistically significantly increased by exposure to phenoxyherbicides [OR, 1.38; 95% confidence interval (CI), 1.06-1.81] and to dicamba (OR, 1.88; 95% CI, 1.32-2.68). Exposure to carbamate (OR, 1.92; 95% CI, 1.22-3.04) and to organophosphorus insecticides (OR, 1.73; 95% CI, 1.27-2.36), amide fungicides, and the fumigant carbon tetrachloride (OR, 2.42; 95% CI, 1.19-5.14) statistically significantly increased risk. Among individual compounds, in multivariate analyses, the risk of NHL was statistically significantly increased by exposure to the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D; OR, 1.32; 95% CI, 1.01-1.73), mecoprop (OR, 2.33; 95% CI, 1.58-3.44), and dicamba (OR, 1.68; 95% CI, 1.00-2.81); to the insecticides malathion (OR, 1.83; 95% CI, 1.31-2.55), 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT), carbaryl (OR, 2.11; 95% CI, 1.21-3.69), aldrin, and lindane; and to the fungicides captan and sulfur compounds. In additional multivariate models, which included exposure to other major chemical classes or individual pesticides, personal antecedent cancer, a history of cancer among first-degree relatives, and exposure to mixtures containing dicamba (OR, 1.96; 95% CI, 1.40-2.75) or to mecoprop (OR, 2.22; 95% CI, 1.49-3.29) and to aldrin (OR, 3.42; 95% CI, 1.18-9.95) were significant independent predictors of an increased risk for NHL, whereas a personal history of measles and of allergy desensitization treatments lowered the risk. We concluded that NHL was associated with specific pesticides after adjustment for other independent predictors.
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PMID:Non-Hodgkin's lymphoma and specific pesticide exposures in men: cross-Canada study of pesticides and health. 1170 Feb 63

The scientific evidence in humans and animals relevant to cancer risks, neurologic disease, reproductive risks, and immunotoxicity of 2,4-D was reviewed. Despite several thorough in vitro and in vivo animal studies, no experimental evidence exists supporting the theory that 2,4-D or any of its salts and esters damages DNA under physiologic conditions. Studies in rodents demonstrate a lack of oncogenic or carcinogenic effects following a lifetime dietary administration of 2,4-D. Epidemiologic studies provide scant evidence that exposure to 2,4-D is associated with soft tissue sarcoma, non-Hodgkin's lymphoma, Hodgkin's disease, or any other cancer. Overall, the available evidence from epidemiologic studies is not adequate to conclude that any form of cancer is causally associated with 2,4-D exposure. There is no human evidence of adverse reproductive outcomes related to 2,4-D. The available data from animal studies of acute, subchronic, and chronic exposure to 2,4-D, its salts, and esters show an unequivocal lack of systemic toxicity at doses that do not exceed renal clearance mechanisms. There is no evidence that 2,4-D in any of its forms activates or transforms the immune system in animals at any dose. At high doses, 2,4-D damages the liver and kidney and irritates mucous membranes. Although myotonia and alterations in gait and behavioral indices are observed after overwhelming doses of 2,4-D, alterations in the neurologic system of experimental animals are not observed with the administration of doses in the microgram/kg/day range. It is unlikely that 2,4-D has any neurotoxic potential at doses below those required to induce systemic toxicity.
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PMID:Review of 2,4-dichlorophenoxyacetic acid (2,4-D) epidemiology and toxicology. 1218 4

Despite showing no evidence of carcinogenicity in laboratory animals, the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has been associated with non-Hodgkin lymphoma (NHL) in some human epidemiology studies, albeit inconsistently. We matched an existing cohort of 2,4-D manufacturing employees with cancer registries in three US states resulting in 244 cancers compared to 276 expected cases. The Standardized Incidence Ratio (SIR) for the 14 NHL cases was 1.36 (95% Confidence Interval (CI) 0.74-2.29). Risk estimates were higher in the upper cumulative exposure and duration subgroups, yet not statistically significant. There were no clear patterns of NHL risk with period of hire and histology subtypes. Statistically significant results were observed for prostate cancer (SIR = 0.74, 95% CI 0.57-0.94), and "other respiratory" cancers (SIR = 3.79, 95% CI 1.22-8.84; 4 of 5 cases were mesotheliomas). Overall, we observed fewer cancer cases than expected, and a non statistically significant increase in the number of NHL cases.
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PMID:Cancer incidence of 2,4-D production workers. 2201 4

Pesticide exposures and immune suppression have been independently associated with the risk of non-Hodgkin lymphoma (NHL), but their joint effect has not been well explored. Data from a case-control study of men from six Canadian provinces were used to evaluate the potential effect modification of asthma, allergies, or asthma and allergies and hay fever combined on NHL risk from use of: (i) any pesticide; (ii) any organochlorine insecticide; (iii) any organophosphate insecticide; (iv) any phenoxy herbicide; (v) selected individual pesticides [1,1'-(2,2,2-trichloroethylidene)bis[4-chlorobenzene]; 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (DDT), malathion, (4-chloro-2-methylphenoxy)acetic acid (MCPA), mecoprop, and (2,4-dichlorophenoxy)acetic acid (2,4-D); and (vi) from the number of potentially carcinogenic pesticides. Incident NHL cases (n = 513) diagnosed between 1991 and 1994 were recruited from provincial cancer registries and hospitalization records and compared to 1,506 controls. A stratified analysis was conducted to calculate odds ratios (ORs) adjusted for age, province, proxy respondent, and diesel oil exposure. Subjects with asthma, allergies, or hay fever had non-significantly elevated risks of NHL associated with use of MCPA (OR = 2.67, 95% confidence interval [CI]: 0.90-7.93) compared to subjects without any of these conditions (OR = 0.81, 95% CI: 0.39-1.70). Conversely, those with asthma, allergies, or hay fever who reported use of malathion had lower risks of NHL (OR = 1.25, 95% CI: 0.69-2.26) versus subjects with none of these conditions (OR = 2.44, 95% CI: 1.65-3.61). Similar effects were observed for asthma and allergies evaluated individually. Although there were some leads regarding effect modification by these immunologic conditions on the association between pesticide use and NHL, small numbers, measurement error and possible recall bias limit interpretation of these results.
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PMID:Pesticide use, immunologic conditions, and risk of non-Hodgkin lymphoma in Canadian men in six provinces. 2239 52

Chlorophenoxy compounds, particularly 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxy)acetic acid (MCPA), are amongst the most widely used herbicides in the United States for both agricultural and residential applications. Epidemiologic studies suggest that exposure to 2,4-D and MCPA may be associated with increased risk non-Hodgkins lymphoma (NHL), Hodgkin's disease (HD), leukemia, and soft-tissue sarcoma (STS). Toxicological studies in rodents show no evidence of carcinogenicity, and regulatory agencies worldwide consider chlorophenoxies as not likely to be carcinogenic or unclassifiable as to carcinogenicity. This systematic review assembles the available data to evaluate epidemiologic, toxicological, pharmacokinetic, exposure, and biomonitoring studies with respect to key cellular events noted in disease etiology and how those relate to hypothesized modes of action for these constituents to determine the plausibility of an association between exposure to environmentally relevant concentrations of 2,4-D and MCPA and lymphohematopoietic cancers. The combined evidence does not support a genotoxic mode of action. Although plausible hypotheses for other carcinogenic modes of action exist, a comparison of biomonitoring data to oral equivalent doses calculated from bioassay data shows that environmental exposures are not sufficient to support a causal relationship. Genetic polymorphisms exist that are known to increase the risk of developing NHL. The potential interaction between these polymorphisms and exposures to chlorophenoxy compounds, particularly in occupational settings, is largely unknown.
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PMID:A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment. 2353 1

2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most commonly used selective herbicides in the world. A number of epidemiology studies have found an association between 2,4-D exposure and non-Hodgkin lymphoma (NHL) but these results are inconsistent and controversial. A previous meta-analysis found no clear association overall but did not specifically examine high-exposure groups. We conducted a systematic review and meta-analysis of the peer-reviewed epidemiologic studies of the associations between 2,4-D and NHL, with a particular focus on high-exposure groups, and evaluations of heterogeneity, dose-response, and bias. A total of 12 observational studies, 11 case-control studies, and one cohort study, were included. The summary relative risk for NHL using study results comparing subjects who were ever versus never exposed to 2,4-D was 1.38 (95% confidence interval (CI), 1.07-1.77). However, in analyses focusing on results from highly exposed groups, the summary relative risk for NHL was 1.73 (95% CI, 1.10-2.72). No clear bias based on study design, exposure assessment methodology, or outcome misclassification was seen. Overall, these findings provide new evidence for an association between NHL and exposure to the herbicide 2,4-D.
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PMID:2,4-dichlorophenoxyacetic acid (2,4-D) and risk of non-Hodgkin lymphoma: a meta-analysis accounting for exposure levels. 2847 29


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