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Non-Hodgkin’s Lymphoma

  • Occupational exposures, animal exposure and smoking as risk factors for hairy cell leukaemia evaluated in a case-control study.
    A population based case-control occupational study of Swedish males with hairy cell leukemia find that exposure to herbicides (OR 2.9), insecticides (OR 2.0), fungicides (OR 3.8) and impregnating agents (OR 2.4) shows increased risk.
    [Nordstrom, M., et al. 1998. Br J Cancer 77(11):2048-2052.]
  • Comprehensive assessment of pesticide use patterns and increased cancer risk
    Pesticides are an essential feature of modern-day agriculture that adds to the list of factors that increase cancer risk. Our study aims to comprehensively evaluate this relationship through a population-based approach that considers confounding variables such as county-specific rates of smoking, socioeconomic vulnerability, and agricultural land. We achieved our goal with the implementation of latent-class pesticide use patterns, which were further modeled among covariates to evaluate their associations with cancer risk. Our findings demonstrated an association between pesticide use and increased incidence of leukemia; non-Hodgkin's lymphoma; bladder, colon, lung, and pancreatic cancer; and all cancers combined that are comparable to smoking for some cancer types. Through our comprehensive analysis and unique approach, our study emphasizes the importance of a holistic assessment of the risks of pesticide use for communities, which may be used to impact future policies regarding pesticides.
    [Gerken, J. et al. (2024) Comprehensive assessment of pesticide use patterns and increased cancer risk, Frontiers. Available at: https://www.frontiersin.org/journals/cancer-control-and-society/articles/10.3389/fcacs.2024.1368086/full. ]
  • Occupational Exposures and Risks of Non-Hodgkin Lymphoma: A Meta-Analysis
    Non-Hodgkin lymphoma (NHL) is a heterogeneous group with different types of diseases. It remains unclear as to what has led to an increase in incidences of NHL, however, chemical substance exposure is known to be one of the risk factors for the disease. Therefore, we performed a systematic review and meta-analysis including case-control, cohort, and cross-sectional observational epidemiological studies to verify the association between occupational exposure to carcinogens and NHL risk. Articles between the years 2000 and 2020 were collected. Two different reviewers performed a blind selection of the studies using the Rayyan QCRI web app. Post-completion, the selected articles were extracted and analyzed via the RedCap platform. Our review resulted in 2719 articles, of which 51 were included in the meta-analysis, resulting in an overall OR of 1.27 (95% CI 1.04-1.55). Furthermore, it was observed that the main occupation associated with the increased risk of NHL was that in which workers are exposed to pesticides. We therefore conclude that the evidence synthesis of the epidemiological literature supports an increased risk for NHL, regardless of subtype, considering occupational exposure to certain chemical compounds, mainly pesticides, benzene, and trichlorethylene, and certain classes of work, primarily in the field of agriculture.
    [Francisco, L.F.V., da Silva, R.N., Oliveira, M.A., dos Santos Neto, M.F., Gonçalves, I.Z., Marques, M.M. and Silveira, H.C., 2023. Cancers, 15(9), p.2600.]
  • Cancer and occupational exposure to pesticides: a bibliometric study of the past 10 years
    Occupational exposure to pesticides has been identified as a major trigger of the development of cancer. Pesticides can cause intoxication in the individuals who manipulate them through either inhalation, ingestion, or dermal contact. Given this, we investigated the association between the incidence of cancer and occupational exposure to pesticides through a bibliometric analysis of the studies published between 2011 and 2020, based on 62 papers selected from the Scopus database. The results indicated an exponential increase in the number of studies published over the past decade, with most of the research being conducted in the USA, France, India, and Brazil, although a further 17 nations were also involved in the research on the association between cancer and pesticides. The principal classes of pesticides investigated in relation to their role in intoxication and cancer were insecticides, herbicides, and fungicides. The types of cancer reported most frequently were multiple myeloma, bladder cancer, non-Hodgkin’s lymphoma, prostate cancer, leukemia, and breast cancer. Despite the known association between pesticides and cancer, studies are still relatively scarce in comparison with the global scale of the use of these xenobiotic substances, which is related to the increasing demand for agricultural products throughout the world
    [Pedroso, T.M.A., Benvindo-Souza, M., de Araújo Nascimento, F., Woch, J., Dos Reis, F.G. and de Melo e Silva, D. Environmental Science and Pollution Research, pp.1-12.]
  • Cancer and occupational exposure to pesticides: an umbrella review
    Purpose
    The aim was to identify the scope of the epidemiology literature reviewed regarding the risk of cancer as related to occupational exposure to pesticides and to compare regulatory toxicity results where feasible.

    Methods
    Review studies of breast, lung, prostate, non-Hodgkin lymphoma, and colorectal cancer were identified from the published literature from 2010 to 2020 using a priori inclusion and exclusion criteria. Epidemiology observations were first assessed and then compared against carcinogenicity profiles derived from regulatory toxicology studies.

    Results
    Several active ingredients were associated with specific cancer but overall, there was neither strong nor consistent epidemiologic data supportive of a positive association between pesticide exposure in occupational settings and cancer. Authors noted common themes related to the heterogeneity of exposure, study design, control for confounders, and the challenge to collect these data reliably and validly with an adequate sample size. Toxicology studies in laboratory animals that assessed carcinogenic potential did not reveal cancer outcomes that were concordant with reported epidemiologic findings.

    Conclusions
    Farming and pesticides represent diverse exposures that are difficult to quantify in epidemiologic studies. Going forward, investigators will need creative and novel approaches for exposure assessment. Integration of epidemiologic and toxicological studies with attention to biological plausibility, mode of toxicological action and relevance to humans will increase the ability to better assess associations between pesticides and cancer.
    [Burns, C.J. and Juberg, D.R. (2021) Cancer and occupational exposure to pesticides: An Umbrella Review, International Archives of Occupational and Environmental Health. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238729/. ]

  • Exposure to Glyphosate-Based Herbicides and Risk for Non-Hodgkin Lymphoma: A Meta-Analysis and Supporting Evidence.
    Glyphosate is the most widely used broad-spectrum systemic herbicide in the world. Recent evaluations of the carcinogenic potential of glyphosate-based herbicides (GBHs) by various regional, national, and international agencies have engendered controversy. We investigated whether there was an association between high cumulative exposures to GBHs and increased risk of non-Hodgkin lymphoma (NHL) in humans. We conducted a new meta-analysis that includes the most recent update of the Agricultural Health Study (AHS) cohort published in 2018 along with five case-control studies. Using the highest exposure groups when available in each study, we report the overall meta-relative risk (meta-RR) of NHL in GBH-exposed individuals was increased by 41% (meta-RR = 1.41, 95% confidence interval, CI: 1.13–1.75). For comparison, we also performed a secondary meta-analysis using high-exposure groups with the earlier AHS (2005), and we calculated a meta-RR for NHL of 1.45 (95% CI: 1.11–1.91), which was higher than the meta-RRs reported previously. Multiple sensitivity tests conducted to assess the validity of our findings did not reveal meaningful differences from our primary estimated meta-RR. To contextualize our findings of an increased NHL risk in individuals with high GBH exposure, we reviewed publicly available animal and mechanistic studies related to lymphoma. We documented further support from studies of malignant lymphoma incidence in mice treated with pure glyphosate, as well as potential links between glyphosate / GBH exposure and immunosuppression, endocrine disruption, and genetic alterations that are commonly associated with NHL or lymphomagenesis. Overall, in accordance with findings from experimental animal and mechanistic studies, our current meta-analysis of human epidemiological studies suggests a compelling link between exposures to GBHs and increased risk for NHL.
    [Zhang, L., Rana, I., Taioli, E., Shaffer, R.M. and Sheppard, L., 2019. Mutation Research/Reviews in Mutation Research.]
  • Cancer risks in a population-based study of 70,570 agricultural workers: results from the Canadian census health and Environment cohort (CanCHEC).
    Agricultural workers may be exposed to potential carcinogens including pesticides, sensitizing agents and solar radiation. Previous studies indicate increased risks of hematopoietic cancers and decreased risks at other sites, possibly due to differences in lifestyle or risk behaviours. Study present findings from CanCHEC (Canadian Census Health and Environment Cohort), the largest national population-based cohort of agricultural workers. Statistics Canada created the cohort using deterministic and probabilistic linkage of the 1991 Canadian Long Form Census to National Cancer Registry records for 1992-2010. A total of 9515 incident cancer cases (7295 in males) occurred in agricultural workers. Among men, increased risks were observed for non-Hodgkin lymphoma (HR = 1.10, 95% CI = 1.00-1.21), prostate (HR = 1.11, 95% CI = 1.06-1.16), melanoma (HR = 1.15, 95% CI = 1.02-1.31), and lip cancer (HR = 2.14, 95% CI = 1.70-2.70). Decreased risks in males were observed for lung, larynx, and liver cancers. Among female agricultural workers there was an increased risk of pancreatic cancer (HR = 1.36, 95% CI = 1.07-1.72). Increased risks of melanoma (HR = 1.79, 95% CI = 1.17-2.73), leukemia (HR = 2.01, 95% CI = 1.24-3.25) and multiple myeloma (HR = 2.25, 95% CI = 1.16-4.37) were observed in a subset of female crop farmers. Exposure to pesticides may have contributed to increased risks of hematopoietic cancers, while increased risks of lip cancer and melanoma may be attributed to sun exposure. The array of decreased risks suggests reduced smoking and alcohol consumption in this occupational group compared to the general population.
    [Kachuri L, Harris MA, MacLeod JS, et al. 2017. BMC Cancer. 17(1):343]
  • Glyphosate Use and Cancer Incidence in the Agricultural Health Study.
    Glyphosate is the most commonly used herbicide worldwide, with both residential and agricultural uses. In 2015, the International Agency for Research on Cancer classified glyphosate as "probably carcinogenic to humans," noting strong mechanistic evidence and positive associations for non-Hodgkin lymphoma (NHL) in some epidemiologic studies. A previous evaluation in the Agricultural Health Study (AHS) with follow-up through 2001 found no statistically significant associations with glyphosate use and cancer at any site.The AHS is a prospective cohort of licensed pesticide applicators from North Carolina and Iowa. Here, we updated the previous evaluation of glyphosate with cancer incidence from registry linkages through 2012 (North Carolina)/2013 (Iowa). Lifetime days and intensity-weighted lifetime days of glyphosate use were based on self-reported information from enrollment (1993-1997) and follow-up questionnaires (1999-2005). We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) using Poisson regression, controlling for potential confounders, including use of other pesticides. All statistical tests were two-sided.Among 54 251 applicators, 44 932 (82.8%) used glyphosate, including 5779 incident cancer cases (79.3% of all cases). In unlagged analyses, glyphosate was not statistically significantly associated with cancer at any site. However, among applicators in the highest exposure quartile, there was an increased risk of acute myeloid leukemia (AML) compared with never users (RR = 2.44, 95% CI = 0.94 to 6.32, Ptrend = .11), though this association was not statistically significant. Results for AML were similar with a five-year (RRQuartile 4 = 2.32, 95% CI = 0.98 to 5.51, Ptrend = .07) and 20-year exposure lag (RRTertile 3 = 2.04, 95% CI = 1.05 to 3.97, Ptrend = .04). In this large, prospective cohort study, no association was apparent between glyphosate and any solid tumors or lymphoid malignancies overall, including NHL and its subtypes. There was some evidence of increased risk of AML among the highest exposed group that requires confirmation.
    [Andreotti G, Koutros S, Hofmann JN, Sandler DP, Lubin JH, et al. 2017. J Natl Cancer Inst. doi: 10.1093/jnci/djx233.]
  • Non-Hodgkin lymphoma among Brazilian agricultural workers: A death certificate case-control study.
    To estimate the non-Hodgkin lymphoma (NHL) mortality risk among agricultural workers in Brazil's southern states, we used death certificates to identify cases of NHL between the ages of 20 and 69 years from residents of nonurban municipalities between 1996 and 2005 (n = 1,317). Controls were randomly selected from those whose underlying cause of death did not include neoplasm or hematological diseases and paired with cases by sex, age, year of death, and state of residence (n = 2,634). Odds of being an agricultural worker among cases and controls were estimated by conditional logistic regression, stratified and adjusted by sex, state, education, and race. An increased risk of death by NHL was observed among agricultural workers 20-39 years old (ORadj = 2.06; 95% CI 95%, 1.20-3.14). Our results suggest that the young agricultural workers from southern Brazil were more likely to die of NHL compared to nonagricultural workers.
    [Boccolini PM, Boccolini CS, Chrisman JR, et al. 2017. Arch Environ Occup Health. 72(3):139-144]
  • Glyphosate pathways to modern diseases V: Amino acid analogue of glycine in diverse proteins
    Glyphosate, a synthetic amino acid and analogue of glycine, is the most widely used biocide on the planet. Its presence in food for human consumption and animal feed is ubiquitous. Epidemiological studies have revealed a strong correlation between the increasing incidence in the United States of a large number of chronic diseases and the increased use of glyphosate herbicide on corn, soy and wheat crops. Glyphosate, acting as a glycine analogue, may be mistakenly incorporated into peptides during protein synthesis. A deep search of the research literature has revealed a number of protein classes that depend on conserved glycine residues for proper function. Glycine, the smallest amino acid, has unique properties that support flexibility and the ability to anchor to the plasma membrane or the cytoskeleton. Glyphosate substitution for conserved glycines can easily explain a link with diabetes, obesity, asthma, chronic obstructive pulmonary disease (COPD), pulmonary edema, adrenal insufficiency, hypothyroidism, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, prion diseases, lupus, mitochondrial disease, nonHodgkin’s lymphoma, neural tube defects, infertility, hypertension, glaucoma, osteoporosis, fatty liver disease and kidney failure. The correlation data together with the direct biological evidence make a compelling case for glyphosate action as a glycine analogue to account for much of glyphosate’s toxicity. Glufosinate, an analogue of glutamate, likely exhibits an analogous toxicity mechanism. There is an urgent need to find an effective and economical way to grow crops without the use of glyphosate and glufosinate as herbicides.
    [Samsel, A. and Seneff, S., 2016. J Biol Phys Chem, 16(6), pp.9-46.]
  • Analysis of Environmental Chemical Mixtures and Non-Hodgkin Lymphoma Risk in the NCI-SEER NHL Study.
    There are several suspected environmental risk factors for non-Hodgkin lymphoma (NHL). The associations between NHL and environmental chemical exposures have typically been evaluated for individual chemicals. Study determined the association between a mixture of 27 correlated chemicals measured in house dust and NHL risk.A population-based case-control study of NHL in four National Cancer Institute-Surveillance, Epidemiology, and End Results centers-Detroit, Michigan; Iowa; Los Angeles County, California; and Seattle, Washington-from 1998 to 2000 was conducted. The WQS index was statistically significantly associated with NHL overall and in the study sites of Detroit, Los Angeles, and Iowa. The most highly weighted chemicals for predicting risk overall were PCB congener 180 and propoxur. Highly weighted chemicals varied by study site; PCBs were more highly weighted in Detroit, and pesticides were more highly weighted in Iowa. An index of chemical mixtures was significantly associated with NHL. Results show the importance of evaluating chemical mixtures when studying cancer risk.
    [Czarnota J, Gennings C, Colt JS, De Roos AJ, et al. 2015. Environ Health Perspect. 123(10):965-70]
  • Insecticide exposure and farm history in relation to risk of lymphomas and leukemias in the Women's Health Initiative observational study cohort.
    In questionnaires, women self-reported history living or working on a farm, personally mixing or applying insecticides, insecticide application in the home or workplace by a commercial service, and treating pets with insecticides. Relationships with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, plasma cell neoplasms, and myeloid leukemia were investigated. The analysis included 76,493 women and 822 NHL cases. Women who ever lived or worked on a farm had 1.12 times the risk of NHL compared to those who did not. Women who reported that a commercial service ever applied insecticides in their immediate surroundings had 65% higher risk of CLL/SLL. Women aged less than 65 years who ever applied insecticides had 87% higher risk of DLBCL. Insecticide exposures may contribute to risk of CLL/SLL and DLBCL.
    [Schinasi LH, De Roos AJ, Ray RM, Edlefsen KL, et al. 2015. Ann Epidemiol. 25(11):803-810.e4]
  • Soft tissue sarcoma, non-Hodgkin's lymphoma and chronic lymphocytic leukaemia in workers exposed to phenoxy herbicides: extended follow-up of a UK cohort.
    Study aimed to provide further information on the possible carcinogenicity of phenoxy herbicides, and in particular their relationship to soft tissue sarcoma (STS), non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL). Authors extended follow-up to December 2012 for 8036 men employed at five factories in the UK which had manufactured phenoxy herbicides, or in a contract spraying business. Mortality from all causes and all cancers was close to expectation, but an excess of deaths from NHL was observed among men who had worked for ≥1 year in jobs with more than background exposure to phenoxy herbicides (19 deaths, SMR 1.85, 95% CI 1.12 to 2.89). Four deaths from STS occurred among men potentially exposed above background (3.3 expected). Findings are consistent with the current balance of epidemiological evidence. If phenoxy herbicides pose a hazard of either STS or NHL, then any absolute increase in risk is likely to be small.
    [Coggon D, Ntani G, Harris EC, et al. 2015. Occup Environ Med.72(6):435-41.]
  • Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis.
    This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL) and occupational exposure to agricultural pesticide active ingredients and chemical groups. Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries. Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL. In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate. Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure. Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world's agriculture, were missing in the literature that were reviewed.
    [Schinasi L, Leon ME. 2014. Int J Environ Res Public Health. 11(4):4449-527.]
  • Non-hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the agricultural health study.
    Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). Study evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were associated with an elevated risk of NHL or NHL subtypes. These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos with NHL subtypes.
    [Alavanja MC, Hofmann JN, Lynch CF, Hines CJ, et al. 2014. PLoS One. 9(10):e109332]
  • Case-control study of risk factors for Non-Hodgkin lymphoma in Mumbai, India.
    In the year 2010, it is estimated that nearly 0.36 million new cases and 0.19 million deaths with Non-Hodgkin lymphoma occurred. In India, among males, NHL incidence rates vary across the country which has encouraged us to conduct a case-control study to study risk factors. The present unmatched hospital-based case-control study conducted at Tata Memorial Hospital included subjects registered between the years 1997-99. There were 390 'lymphoma cases' and 1,383 'normal controls. Data on age, tobacco habits, occupational history, dietary factors, tea, coffee were collected by the social investigators. Univariate and multivariate methods were applied for obtaining the odds ratios for risk factors. In the study, cigarette smoking (OR=2.0) and bidi smoking (OR=2.8), were associated with excess risk of lymphoma. Among the dietary items, only consumption of mutton showed 7.3-fold significant excess risk for lymphoma. Consumption of milk showed a 6-fold excess risk (OR=1.5); while coffee showed a 50% reduction in risk for lymphoma. Among occupational exposure, exposure to use of pesticides showed 3-fold excess risk for lymphoma.
    [Balasubramaniam G, Saoba S, Sarade M, Pinjare S. 2013. Asian Pac J Cancer Prev. 14(2):775-80.]
  • Exposures to multiple pesticides and the risk of Hodgkin lymphoma in Canadian men.
    Study's aim was to determine the risk of Hodgkin lymphoma (HL) associated with exposures to multiple pesticides grouped by various classes, including carcinogenic classifications. Data collected in the Cross-Canada Study of Pesticides and Health, a population-based incident case-control study in six provinces conducted between 1991 and 1994, were analyzed using unconditional logistic regression. Overall, there was an increase in the risk of HL among all subjects who reported use of five or more insecticides (OR 1.88) and among subjects younger than 40 who reported use of two acetylcholinesterase inhibitors (OR 3.16). There was an elevated odds ratio associated with reported use of three or more probably carcinogenic pesticides (OR 2.47), but no increase in risk for use of possibly carcinogenic pesticides. The risk of HL from reported use of fungicides or any pesticides was greater for cases diagnosed before age 40 than for cases diagnosed at or after age 40. This study found associations between HL and fungicides, insecticides, specifically acetylcholinesterase inhibitors, and pesticides previously identified as probable human carcinogens.
    [Navaranjan G, Hohenadel K, Blair A, Demers PA, et al. 2013. Cancer Causes Control. 24(9):1661-73]
  • Hypospadias and residential proximity to pesticide applications.
    Examine the association of hypospadias with residential proximity to commercial agricultural pesticide applications. The study population included male infants born from 1991 to 2004 to mothers residing in 8 California counties. Cases (n = 690) were ascertained by the California Birth Defects Monitoring Program; controls were selected randomly from the birth population (n = 2195). Authors determined early pregnancy exposure to pesticide applications within a 500-m radius of mother's residential address, using detailed data on applications and land use. Forty-one percent of cases and controls were classified as exposed to 57 chemical groups and 292 chemicals. Despite >500 statistical comparisons, there were few elevated odds ratios with confidence intervals that excluded 1 for chemical groups or specific chemicals. Those that did were for monochlorophenoxy acid or ester herbicides; the insecticides aldicarb, dimethoate, phorate, and petroleum oils; and adjuvant polyoxyethylene sorbitol among all cases; 2,6-dinitroaniline herbicides, the herbicide oxyfluorfen, and the fungicide copper sulfate among mild cases; and chloroacetanilide herbicides, polyalkyloxy compounds used as adjuvants, the insecticides aldicarb and acephate, and the adjuvant nonyl-phenoxy-poly(ethylene oxy)ethanol among moderate and severe cases. Odds ratios ranged from 1.9 to 2.9.Most pesticides were not associated with elevated hypospadias risk. For the few that were associated, results should be interpreted with caution until replicated in other study populations.
    [Carmichael SL, Yang W, Roberts EM, et al. 2013. Pediatrics. 132(5):e1216-26]
  • Non-Hodgkin lymphoma and pesticide exposure in Turkey.
    The study used data from 1995 to 2010 on the patients who were histopathologically diagnosed with NHL during these years. An increase in the NHL incidence over the years was identified, with a 2.42-fold increment found from 1995 to 2005 and a 2.77 fold elevation from 1995 to 2010. The use of pesticides increased 1.89 fold over the same period.Study investigated the relationship of the pesticides used with NHL patients diagnosed during the same year. Since the time elapsing after exposure to pesticides until the development of cancer is not clear, no comparison can be made at present. We believe that the increase in use of pesticides since 1995 may be associated with the increase in the incidence of NHL and therefore that further studies on the issue including measurements of serum pesticide levels, are required.
    [Yildirim M, Karakilinc H, Yildiz M, Kurtoglu E, et al. 2013. Asian Pac J Cancer Prev. 14(6):3461-3.]
  • Non-hodgkin's lymphoma and work in agriculture: Results of a two case-control studies in Saskatchewan, Canada.
    The objective was to examine the association between non-Hodgkin's lymphoma (NHL) and farming-related activities, gender, pesticides exposure, and exposure to chemicals other than pesticides in Saskatchewan. Male and female study participants were taken from two separate case-control studies conducted in Saskatchewan province, Canada. A case was defined as any man or woman aged 19 years and older with a first diagnosis of NHL registered by the Saskatchewan Cancer Agency during the study period. Farming exposure and exposure to pesticides-contaminated cloths were related to an increased risk of NHL. Exposure to pesticides was strongly associated with an increased risk of NHL, especially for men.
    [Karunanayake CP, Dosman JA, Pahwa P. 2013. Indian J Occup Environ Med.17(3):114-21]
  • Pesticide use and non-Hodgkin's lymphoma mortality in Brazil.
    Brazil is one of the major pesticide consumers in the world. The continuous exposure to these substances may be etiologically associated with the development of Non-Hodgkin's Lymphoma (NHL). Study's goal was to Estimate the correlation between the per capita sales of pesticides in 1985 (exposure) and NHL mortality rates between 1996 and 2005 (outcome), by Brazilian micro-regions. A moderate correlation between per capita pesticides consumption and standardized mortality rate for NHL was observed (r=0.597). In addition, using the lowest quartile of pesticide consumption as a reference, the higher the quartile of pesticide consumption, the higher was NHL mortality risk: men - (second quartile - MRR=1.69, CI 95% 1.68-1.84; third quartile - MRR=2.41, CI 95% 2.27-2.57; fourth quartile - MRR=2.92, CI 95% 2.74-3.11) and females (second quartile - MRR=1.87, CI 95% 1.69-2.06; third quartile - MRR=2.28, IC 95% 2.10-2.47; fourth quartile - MRR=3.20; CI 95% 2.98-3.43).Results suggest that pesticide exposure may play a role in the etiology of NHL.
    [Boccolini Pde M, Boccolini CS, Chrisman Jde R, et al. 2013. Int J Hyg Environ Health. 216(4):461-6.]
  • A prospective study of organochlorines in adipose tissue and risk of non‑Hodgkin lymphoma.
    Purpose here was to examine associations between organochlorine concentrations in prediagnostic adipose tissue samples and the risk of NHL.Authors conducted a case–cohort study using a prospective Danish cohort of 57,053 persons enrolled between 1993 and 1997 and measured concentrations of 8 pesticides and 10 polychlorinated biphenyl (PCB) congeners in adipose tissue collected upon enrollment. Results found a higher risk of NHL in association with higher adipose tissue levels of DDT, cis-nonachlor, and oxychlordane, but no association with PCBs. This is the first study of organochlorines and NHL using prediagnostic adipose tissue samples in the exposure assessment and provides new environmental health evidence that these organochlorines contribute to NHL risk.
    [Bräuner EV, Sørensen M, Gaudreau E, LeBlanc A, et al. 2012. Environ Health Perspect.120(1):105-11.]
  • Pesticide use, immunologic conditions, and risk of non-Hodgkin lymphoma in Canadian men in six provinces.
    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. 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. Subjects with asthma, allergies, or hay fever had non-significantly elevated risks of NHL associated with use of MCPA (OR = 2.67) compared to subjects without any of these conditions (OR = 0.81). Conversely, those with asthma, allergies, or hay fever who reported use of malathion had lower risks of NHL (OR = 1.25) versus subjects with none of these conditions (OR = 2.44). 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.
    [Pahwa M, Harris SA, Hohenadel K, McLaughlin JR, et al.2012.Int J Cancer. 131(11):2650-9.]
  • Increased risk of non-Hodgkin lymphoma and serum organochlorine concentrations among neighbors of a municipal solid waste incinerator.
    Study investigated organochlorines and the risk of NHL among neighbors of a French MSWI with high levels of dioxin emissions (Besançon, France), using serum concentrations to assess exposure. Risks of NHL associated with each lipid-corrected serum concentration were estimated using exact logistic regression. The pesticides β-hexachlorocyclohexane (odds ratio [OR]=1.05, 95% confidence interval [CI]=1.00-1.12, per 10 ng/g lipid) and p,p' dichloro-diphenyl-trichloroethane (DDT) (OR=1.20, 95% CI=1.01-1.45, per 10 ng/g lipid) were associated with NHL risk. Evidence indicated an increased NHL risk associated with cumulative WHO(1998)-toxic equivalency factor (TEQ) concentrations (dioxins, OR=1.12, 95% CI=1.03-1.26; furans, OR=1.16, 95% CI=1.03-1.35; dioxin-like PCBs, OR=1.04, 95% CI=1.00-1.07; and total TEQ, OR=1.04, 95% CI=1.01-1.05), as well as with non dioxin-like PCBs (OR=1.02, 95% CI=1.01-1.05, per 10 ng/g lipid). Most congener-specific associations were statistically significant. This study provides strong and consistent support for an association between serum cumulative WHO(1998)-TEQ concentrations, at levels experienced by people residing in the vicinity of a polluting MSWI, and risk of NHL.
    [Viel JF, Floret N, Deconinck E, Focant JF, et al. 2011. Environ Int. 37(2):449-53.]
  • Mortality of US pentachlorophenol production workers through 2005.
    A cohort of 2122 US pentachlorophenol (PCP) production workers from four plants in the National Institute for Occupational Safety and Health Dioxin Registry was exposed to PCP and to polychlorinated dibenzo-p-dioxin and dibenzofuran contaminants of PCP production. A subcohort of 720 was also exposed to 2,3,7,8-tetrachlorodibenzodioxin, a contaminant of trichlorophenol (TCP) while using TCP or a TCP derivative. PCP and several production contaminants have been implicated as animal carcinogens. A priori hypotheses were that the cohort would have elevated standardized mortality ratios (SMRs) for aplastic anemia, soft-tissue sarcoma, and non-Hodgkin lymphoma, as suggested by human studies, and for leukemia and liver, adrenal, thyroid, and parathyroid cancer, as suggested by animal studies. From 1940 to 2005 1165 deaths occurred with an overall SMR of 1.01 [95% confidence limits (CI), 0.95-1.07]. Overall cancer mortality (326 deaths, SMR 1.17, CI 1.05-1.31) was in statistically significant excess. There were excess deaths for trachea, bronchus and lung cancers (126 deaths, SMR 1.36, CI 1.13-1.62), non-Hodgkin lymphoma (17 deaths, SMR 1.77, CI 1.03-2.84), chronic obstructive pulmonary disease (63 deaths, SMR 1.38, CI 1.06-1.77), and medical complications (5 deaths, SMR 3.52, CI 1.14-8.22).The excess of cancers of a priori interest, non-Hodgkin lymphoma and leukemia, provide some support for the carcinogenicity of PCP, however, further studies with more detailed exposure assessment are needed.
    [Ruder AM, Yiin JH. 2011.Chemosphere. 83(6):851-61.]
  • Occupational exposure to terbufos and the incidence of cancer in the Agricultural Health Study
    Study investigated associations between use of terbufos and the incidence of cancer. The Agricultural Health Study is a prospective cohort study of 57,310 licensed pesticide applicators from Iowa and North Carolina. Detailed information about 50 pesticides, including terbufos, and potential confounders was obtained from self-administered questionnaires. Overall cancer risk was slightly increased among terbufos users. Suggestive associations were observed between terbufos use and cancers of the prostate and lung, leukemia, and non-Hodgkin's lymphoma, although the exposure-response gradients were non-monotonic and p for trends were not significant. However, cautious interpretation of these results is warranted by the lack of existing experimental and epidemiologic evidence to support carcinogenic effects of terbufos.
    [Bonner, M.R., et al. 2010. Cancer Causes Control 21(6):871-7]
  • High risk occupations for non-Hodgkin's lymphoma in New Zealand: case-control study.
    Previous studies into occupational risk factors for non-Hodgkin's lymphoma (NHL) in New Zealand have indicated that farmers and meat workers are at increased risk for these neoplasms. A new nationwide case-control study was conducted to assess whether previously observed associations persist and to identify other occupations that may contribute to the risk of NHL in the New Zealand population. A total of 291 incident cases of NHL (age 25-70 years) notified to the New Zealand Cancer Registry during 2003 and 2004, and 471 population controls, were interviewed face-to-face. The questionnaire collected demographic information and a full occupational history. The relative risk for NHL associated with ever being employed in particular occupations and industries was calculated by unconditional logistic regression adjusting for age, sex, smoking, ethnicity and socioeconomic status. Estimates were subsequently semi-Bayes adjusted to account for the large number of occupations and industries being considered. An elevated NHL risk was observed for field crop and vegetable growers (OR 2.74, 95% CI 1.04 to 7.25) and horticulture and fruit growing (OR 2.28, 95% CI 1.37 to 3.79), particularly for women (OR 3.44, 95% CI 0.62 to 18.9; OR 3.15, 95% CI 1.50 to 6.61). Sheep and dairy farming was not associated with an increased risk of NHL. Meat processors had an elevated risk (OR 1.97, 95% CI 0.97 to 3.97), as did heavy truck drivers (OR 1.98, 95% CI 0.92 to 4.24), workers employed in metal product manufacturing (OR 1.92, 95% CI 1.12 to 3.28) and cleaners (OR 2.11, 95% CI 1.21 to 3.65). After semi-Bayes adjustment the elevated risks for horticulture and fruit growing, metal product manufacturing and cleaners remained statistically significant, representing the most robust findings of this study. This study has confirmed that crop farmers and meat workers remain high risk occupations for NHL in New Zealand, and has identified several other occupations and industries of high NHL risk that merit further study.
    [Mannetje, A., et al. 2008. Occupational and Environmental Medicine 65:354-363]
  • Pesticide exposure as risk factor for non-Hodgkin lymphoma including histopathological subgroup analysis.
    A Swedish population based case-control study of male and female NHL patients finds the highest risk is for exposure to: herbicides; MCPA with a latency period greater than ten years; glyphosate ; and, glyphosate exposure with a latency period of greater than ten years . When different NHL subtypes are analyzed: (a) diffuse large B-cell lymphoma is significantly associate with exposure to phenoxyacetic acids and especially for MCPA; (b) small lymphocytic lymphoma/chronic lymphocytic leukemia is associated with exposure to phenoxy herbicides, MCPA , and glyphosate ; (c) the category “other specific B-cell lymphoma (mantle cell lymphoma, marginal zone lymphoma)” an association is found for exposure to phenoxyacetic acids, MCPA and glphyosate; and (d) the category “unspecific NHL” subtypes are associated with herbicides, phenoxyacetic acids, MCPA and glyphosate.
    [Eriksson, M., et al. 2008. Int J Cancer 123(7):1657-1663]
  • Atopy, exposure to pesticides and risk of non-Hodgkin lymphoma
    Although the Australian population based case control study did not find a clear connection with asthma and pesticide exposure and NHL, it did find an increased risk of NHL with occupational pesticide exposure and a history of asthma as well as with occupational pesticide exposure an no history of asthma.
    [Vajdic, C.M., et al. 2007. Int J Cancer 120(10):2271-2274]
  • Household exposure to pesticides and risk of childhood hematopoietic malignancies: The ESCALE study (SFCE)
    A case-control study in France finds prenatal insecticide use is significantly associated with childhood lymphoblastic and myelobastic NHL, mainly for Burkitt lymphoma, and finds paternal household use of pesticides is associated with NHL. Household use of any pesticide during pregnancy is significantly more frequent in NHL cases.
    [Rudant, J., et al. 2007. Environmental Health Perspectives 115(12):1787-1793]
  • Occupational exposure to organochlorine insecticides and cancer incidence in the Agricultural Health Study
    A NIH prospective cohort study of licensed pesticide applicators in Iowa and North Carolina finds a significant increase in risk for NHL and lindane.
    [Purdue, M.P., et al. 2007. Int J Cancer 120(3):642-649]
  • Occupational exposure to pesticides and risk of hematopoietic cancers: meta-analysis of case-control studies
    A meta-analysis of 13 case-control studies on hematopoeietic cancers finds that occupational pesticide exposure greater than ten years significantly increases risk of NHL (OR 1.65).
    [Merhi, M, et al. 2007. Cancer Causes Control 18(10):1209-1226]
  • Agricultural pesticide use and risk of t(14;18)-defined subtypes of non-Hodgkin lymphoma.
    A population-based, case-control study in Nebraska looking at different molecular subtypes of NHL discovered that the risk of t(14;18)-positive NHL subtype is significantly elevated among farmers who used animal insecticides (OR 2.6), crop insecticides (OR 3.0), herbicides (OR 2.9) and fumigants (5.0 OR) and that there was no increased risk of t(14;18)-negative NHL subtype for these pesticides, which may explain some of the inconsistencies in epidemiological study of NHL and pesticide exposure. They also find that the risk increases with a longer duration of use.
    [Chiu, B., et al. 2006. Blood 108(4):1363-1369]
  • Cancer and pesticides: an overview and some results of the Italian multicenter case-control study on hematolymphopoietic malignancies
    A population based case-control study in Italy finds a significant increase in risk of NHL for occupational exposure to 2,4D.
    [Miligi, L., et al. 2006. Ann N Y Acad Sci 1076:366-377]
  • Integrative assessment of multiple pesticides as risk factors for non-Hodgkin's lymphoma among men
    A study using three National Cancer Institute case-controls of NHL in Iowa, Minnesota, Kansas, and Nebraska farmers finds coumaphos (OR 1.7), diazinon (OR 1.7), and glyphosate (OR 1.6) are associated with an increase in NHL incidence.
    [De Roos, A.J., et al. 2003. Occupational and Environmental Medicine 60(9):e11]
  • Exposure to pesticides as risk factor for non-Hodgkin's lymphoma and hairy cell leukemia: pooled analysis of two Swedish case-control studies.

    previously been reported. To further elucidate the importance of phenoxyacetic acids and other pesticides in the etiology of NHL a pooled analysis was performed on two case-control studies, one on NHL and another on hairy cell leukemia (HCL), a rare subtype of NHL. The studies were population based with cases identified from cancer registry and controls from population registry. Data assessment was ascertained by questionnaires supplemented over the telephone by specially trained interviewers. The pooled analysis of NHL and HCL was based on 515 cases and 1141 controls. Increased risks in univariate analysis were found for subjects exposed to herbicides (OR 1.75, CI 95% 1.26-2.42), insecticides (OR 1.43, CI 95% 1.08-1.87), fungicides (OR 3.11, CI 95% 1.56-6.27) and impregnating agents (OR 1.48, CI 95% 1.11-1.96). Among herbicides, significant associations were found for glyphosate (OR 3.04, CI 95% 1.08-8.52) and 4-chloro-2-methyl phenoxyacetic acid (MCPA) (OR 2.62, CI 95% 1.40-4.88). For several categories of pesticides the highest risk was found for exposure during the latest decades before diagnosis. However, in multivariate analyses the only significantly increased risk was for a heterogeneous category of other herbicides than above.


    [Hardell, L., et al. 2002. Leuk Lymphoma 43(5):1043-1049]
  • Agricultural risk factors for t(14;18) subtypes of non-Hodgkin's lymphoma.
    A study using a case-control study of male farmers in Iowa and Minnesota finds that the t(14;18)-positive subtypes of NHL is associated with farming (OR 1.4), lindane (OR 2.3), atrazine (OR 1.7) and fungicides (OR 1.8) and no association with t(14;18)-negative NHL
    [Schroeder, J., et al. 2001. Epidemiology 12(6):701-709]
  • Non-Hodgkin's lymphoma and specific pesticide exposures in men: cross-Canada study of pesticides and health.
    A Canadian multi-center population based incident case control study among men finds an increase risk of NHL for exposure to dicamba, carbamates, OPs, amide fungicides and fumigant carbon tetrachloride, mecoprop, malathion and carbaryl.
    [McDuffie, H., et al. 2001.Cancer Epidemiology, Biomarkers & Prevention 10:1155-1163]
  • Leukemia and Non-Hodgkin's Lymphoma in Childhood and Exposure to Pesticides: Results of a Register-based Case-Control Study in Germany

    Previous studies have suggested an association between exposure to pesticides and different types of childhood cancer. This paper presents results from a population-based case-control interview study of parents of children less than 15 years of age, which was conducted in the states of West Germany from 1993 to 1997. Cases were 1,184 children with leukemia, 234 with non-Hodgkin's lymphoma, and 940 with a solid tumor; 2,588 controls were also included. Parental occupational exposures were found to be related to childhood cancer regardless of the time period of exposures and the type of cancer. This finding might partially be explained by different recall of past exposures by the parents of cases and controls. Residential use of insecticides was assodated with childhood lymphoma: both extermination of insects by professional pest controllers (odds ratio (OR) = 2.6, 95% confidence interval (CI): 1.2, 5.7) and frequency of parental use of household insecticides (pfor trend = 0.02) were significant risk factors for this diagnosis. The use of pesticides on farms was weakly related to childhood leukemia (OR = 1.5, 95% CI: 1.0, 2.2), while their use in gardens was not assodated with childhood leukemia (OR = 1.0, 95% CI: 0.8, 1.2). The major strengths of this study were the population base and the large number of cases and controls included; a drawback was assessment of expasure on the basis of parental interviews. The data provide some evidence for an increased leukemia risk for children living on farms and for an association between use of household pesticides and risk of childhood leukemia or lymphoma. 
    [Meinert, R., et al. 2000. American Journal of Epidemiology 151(7):639-646]

  • Pesticide exposures in children with non-Hodgkin lymphoma.
    A case-control study in the U.S. finds a significant association between risk of childhood NHL and frequency of reported prenatal home pesticide use, and professional treatments in the home. Postnatal home pesticide exposure also shows a significant association . In children, elevated risk for T-cell, B-cell lymphomas, lymphoblastic, large cell, and Burkitt morphologies are found.
    [Buckley, J.D., et al. 2000. Cancer 89(11):2315-2321]
  • A case-control study of non-Hodgkin lymphoma and exposure to pesticides
    A population based case-control study in Sweden finds an increased risk for NHL for people exposed to herbicides, specifically significant is exposure to MCPA, and fungicides.
    [Hardell, L., et al. 1999. Cancer 85(6):1353-1360]
  • Meta-analyses of non-Hodgkin's lymphoma and farming.
    A meta-analyses of 36 studies on NHL and farming suggests that male U.S. farmers have a slightly elevated risk of NHL.
    [Khuder, S.A., et al 1998. Scand J Work Environ Health 24(4):255-261]
  • Cancer in offspring of parents engaged in agricultural activities in Norway: incidence and risk factors in the farm environment.
    A cohort study of cancer in offspring of parents working in Norway horticulture finds parental pesticide purchase associated with childhood NHL.
    [Kristensen, P., et al. 1996. Int J Cancer 65(1):39-50]
  • Cancer incidence among Icelandic pesticide users
    A small cohort study in Iceland shows that female licensed pesticide applicators for agricultural purposes have a significant increased incidence for cancers of the lymphatic and hematopoietic tissue in women.
    [Zhong, Y. and Rafnsson, V. 1996. International Journal of Epidemiology 25(6):1117-1124.]
  • Farming, pesticide use and hairy-cell leukemia.
    This paper analyzes the role of farming and pesticide exposures in the occurrence of hairy-cell leukemia (HCL). The study included 226 men with HCL and 425 matched hospital referents. Pesticide exposure was assessed by expert review of detailed interview data on occupational histories and agricultural activities and exposures. Altogether, 77 cases and 116 referents had farmed for at least six months, giving an odds ratio (OR) of 1.5 [95% confidence interval (95% CI) 1.0-2.2]. Forage growing was reported by 20.8% of the cases and 11.1% of the referents and was associated with HCL (OR 2.8, 95% CI 1.6-4.9), even among farmers who had never handled pesticides (OR 3.4, 95% CI 1.0-11.0). A significant association was found between HCL and pesticide use, the overall odds ratios for insecticide, fungicide, and herbicide use ranging from 1.5 to 2.4. Organophosphorus insecticides were the only agrochemicals with a positive association with HCL after other pesticide exposures, smoking, and forage growing were accounted for. A clear-cut negative interaction was found between smoking and exposure to organophosphorus insecticides. A multivariate analysis yielded odds ratio estimates of 2.8 (95% CI 1.4-5.6) for exposure to forage and 7.5 (95% CI 0.9-61.5) for nonsmokers exposed to organophosphorus insecticides. The present study argues for a role of organophosphorus insecticides in HCL among nonsmoking farmers and shows an unexpected association with forage growing. No evidence of an association with phenoxyacetic acids, triazines, or organochlorine insecticides was found.
    [Clavel, J., et al. 1996. Scand J Work Environ Health 22(4):285-293]
  • Proportionate mortality study of golf course superintendents.
    A proportionate mortality study of a cohort of 686 golf course superintendents finds an elevated number deaths from brain cancer (PMR 234), large intestine cancer (PMR 175), NHL (PMR 237), and prostate cancer (PMR 293).
    [Kross, B.C., et al. 1996. Am J Ind Med 29(5):501-506]
  • Soft tissue sarcoma and non-Hodgkin's lymphoma in workers exposed to phenoxy herbicides, chlorophenols, and dioxins: two nested case-control studies

    Abstract

    We examined the effect of exposure to chemicals present in the production and spraying of phenoxy herbicides or chlorophenols in two nested case-control studies of soft tissue sarcoma and non-Hodgkin's lymphoma. Eleven sarcoma and 32 lymphoma cases occurring within an international cohort were matched for age, sex, and country of residence with 55 and 158 controls, respectively. Exposures to 21 chemicals or mixtures were estimated by three industrial hygienists who were blind to the subject's case-control status. Excess risk of soft tissue sarcoma was associated with exposure to any phenoxy herbicide [odds ratio (OR) = 10.3; 95% confidence interval (CI) = 1.2-91] and to each of the three major classes of phenoxy herbicides (2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, and 4-chloro-2-methylphenoxyacetic acid), to any polychlorinated dibenzodioxin or furan (OR = 5.6; 95% CI = 1.1-28), and to 2,3,7,8-tetrachlorodibenzo-p-dioxin (OR = 5.2; 95% CI = 0.85-32). Sarcoma risk was not associated with exposure to raw materials or other process chemicals. In the non-Hodgkin's lymphoma study, associations were generally weaker than those found in the study on sarcoma. These findings indicate that workers exposed to phenoxy herbicides and their contaminants are at a higher risk of soft tissue sarcoma.


    [Kogevinas, M. et al. (1995) ‘Soft tissue sarcoma and Non-Hodgkinʼs lymphoma in workers exposed to phenoxy herbicides, chlorophenols, and dioxins’, Epidemiology, 6(4), pp. 396–402. doi:10.1097/00001648-199507000-00012. ]
  • Non-Hodgkin's lymphoma and agricultural practices in the prairie provinces of Canada.
    A follow-up to a previous cohort study in Canada finds a significant increase risk for fatal NHL for male farmers according to acres sprayed herbicides
    [Morrison, H.I., et al. 1994. Scand J Work Environ Health 10(1):42-47]
  • The role of agricultural pesticide use in the development of non-Hodgkin's lymphoma in women
    A population-based case control study in Nebraska finds that NHL risk is significantly increased for woman who handle OP insecticides, for use of chlorinated hydrocarbon insecticides, and for chlorinated hydrocarbon insecticide use on cattle. The study finds that pesticide related risk are grater for woman with a family history of cancer.
    [Zahm, S., et al. 1993. Archives of Environmental Health 48(5):353-358]
  • Herbicides and Cancer
    Herbicides are a heterogeneous class of chemicals used in agriculture, forestry, and urban settings to kill weeds, shrubs, and broad-leaved trees. The role of herbicides in the etiology of cancer is controversial. Potential studies for review were identified through a MEDLINE 1 search and from a check of references in related review articles. This review of the literature shows reasonable evidence suggesting that occupational exposure to phenoxy herbicides results in increased risk of developing non-Hodgkin's Iymphoma. Several studies have noted large increases in risk of soft-tissue sarcomas with phenoxy herbicide exposure. In contrast, others have failed to observe increased risks, and evidence of an exposure—risk relationship is lacking. Although there have been too few appropriate studies for adequate assessment of risk of cancer at other sites, some findings have linked herbicide exposure with cancers of the colon, lung, nose, prostate, and ovary as well as to leukemia and multiple myeloma. Future studies must better identify and quantify the nature of herbicide exposures. In the interim, it seems only prudent to monitor and promote safety practices among persons occupationally exposed to phenoxy herbicides, particularly farmers and professional sprayers.
    [Morrison, H.I., et al. 1992. J Natl Cancer Inst 84(24):1866-1874]
  • Pesticides and Other Agricultural Risk Factors for Non-Hodgkin's Lymphoma among Men in Iowa and Minnesota
    A population based study of white male farmers finds a significant increase in risk for (a) diffuse NHL and organophosphates (OP) on crops, non-halogenated aliphatic OP on crops, cyclodiene chlorinated hydrocarbons used on livestock, and triazine herbicides; (b) small lymphocytic NHL with “natural product insecticides used on livestock” (although nowhere in the study does it define “natural”), and halongenated aromatic OP for livestock); and, (c) other and unclassified forms of NHL and chlorinated hydrobarbon insecticides for crops, cyclodienes for crops, and halogenated aliphatic OPs used on livestock
    [Cantor, K., et al. 1992. Cancer Research 52:2447-2455]
  • A case-control study of non-Hodgkin's lymphoma and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in eastern Nebraska.
    A population based case-control study in Nebraska finds a slight increase NHL risk for men who mix or apply 2,4-D. A significant risk is found for: men who mix or apply 2,4-D for 20 days or more a year; men who mix or apply 2,4-D and fungicides; men who mix or apply 2,4-D and OPs; and, men who mix or apply 2,4-D, fungicides and OPs.
    [Zahm, S., et al. 1990. Epidemiology 1(5):349-356]
  • Cancer mortality in the U.S. flour industry
    A nested case control mortality study of workers employed in U.S. flour mills, where according to the study author’s, “pesticides are used more frequently than in other segments of the industry,” an increased risk for NHL (OR 4.2) is found.
    [Alavanja, M.C., et al. 1990. J Natl Cancer Inst 82(10):840-848]
  • Mortality study of Canadian male farm operators: cancer mortality and agricultural practices in Saskatchewan.
    A cohort mortality study of male Saskatchewan farmer finds a significant dose-response relationship is found between risk of NHL and acres sprayed with herbicides
    [Wigle, D., et al. 1990. Journal of the National Cancer Institute 82(7):575-582]
  • Soft tissue sarcoma and non-Hodgkin's lymphoma in relation to phenoxyherbicide and chlorinated phenol exposure in western Washington.
    A population-based case-control study in Washington state finds an elevated risk of NHL among male forestry herbicide applicators and for men that are potential exposed to phenoxy herbicides in any occupation for 15 or more years prior to their cancer diagnosis.
    [Woods, J.S., et al. 1987. J Natl Cancer Inst 78(5):899-910]
  • Agricultural herbicide use and a risk of lymphoma and soft-tissue sarcoma.
    A population based case control study in Kansas finds farm herbicide use increases risk associated with NHL; risk increased significantly for those men exposed to herbicides more than 20 days a year; and, those men that frequently mixed or applied herbicides themselves also have a significant increased risk to phenoxyacetic acid herbicides, specifically 2,4D.
    [Hoar, S., et al. 1986. Journal of the American Medical Association 259(9): 1141-1147]
  • Malignant lymphoma and multiple myeloma linked with agricultural occupations in a New Zealand Cancer Registry-based study.
    A case-control study of New Zealand agriculture and forestry workers finds a significant excess of patients with nodular lymphoma, mycosis fungoldes, and NHL.
    [Pearce, N.E., et al. 1985. Am J Epidemiol 121(2):225-237]
  • Farming and mortality from non-Hodgkin's lymphoma: A case-control study
    A case‐control study of non‐Hodgkin's lymphoma (NHL) and its subtypes among males was conducted using computerized mortality listings from the State of Wisconsin for the years 1968‐1976. Age, year of death, race, county of usual residence, marital status, and usual occupation were abstracted for the 774 records of male deaths due to NHL and a matched series of deaths due to other causes. The frequency of farming occupation among NHL cases was compared to the frequency among controls, and odds ratios (OR) were calculated. Farming was more common among cases than among controls (OR=1.22). The association of NHL with farming occupation was greater among decedents under 65 years of age (ORequlas;1.7) than among those who were older. The younger decedents were at higher risk of reticulum‐cell sarcoma (ORequlas;2.7) than of other cell types. The strength of the association increased over the 9‐year study period. County levels of selected agricultural characteristics were used as surrogate measures of farming exposures in residence counties of farmers and were summarized by factor analysis. Major findings were of elevated risk among younger farmers for reticulum‐cell sarcoma in counties high in summary measures of general agricultural activity (ORequlas;3.2), of small grain acreage and acres treated with insecticides (ORequlas;6.6), and of wheat acreage (ORequlas;4.4). Given the limitations of the data, further investigation of non‐Hodgkin's lymphoma in farmers is warranted.
    [Cantor, KP. 1982. Int J Cancer 29(3):239-247]