ABSTRACT

We conducted an integrative literature review of published studies on pesticide and cancer exposure, focusing on farmers, rural population, pesticide applicators, and rural workers. The Medline/PubMed was used as searching database. After the retrieval, 74 articles were selected according to pre-established criteria, which design involved 39 case-controls, 32 cohorts, 2 ecological ones, and 1 cross-sectional. Among them, 64 studies showed associations between pesticides and cancer while 10 did not find any significant association. The studies found 53 different types of pesticides significantly associated with at least one type of cancer and 19 different types of cancers linked to at least one type of pesticide. Although few studies presented contradictory results, the sole fact of being a farmer or living near crops or high agricultural areas have also been used as a proxy for pesticide exposure and significantly associated with higher cancer risk. The literature well illustrates the case of prostate cancer, Non-Hodgkin lymphoma, leukemia, multiple myeloma, bladder and colon cancers. Studies are recommended to further investigate the relationship between pesticide and neoplasm of testis, breast, esophagus, kidney, thyroid, lip, head and neck, and bone.

KEYWORDS
Neoplasms; Agrochemicals; Occupational diseases; Review

RESUMO

Trata-se de revisão integrativa da literatura sobre estudos publicados em relação à exposição a agrotóxicos e câncer, com foco em agricultores, população rural, aplicadores de agrotóxicos e trabalhadores rurais. A busca dos artigos foi realizada por meio do banco de dados Medline/PubMed. Após a triagem, 74 artigos foram selecionados de acordo com critérios pré-estabelecidos, sendo 39 caso-controle, 32 coortes, dois ecológicos e um transversal. Desses, 64 estudos mostraram associação entre agrotóxicos e câncer, enquanto dez não encontraram associação significativa. Nesses 64, 53 diferentes tipos de agrotóxicos foram significativamente associados com pelo menos um tipo de câncer e, inversamente, 19 diferentes tipos de câncer foram associados a pelo menos um tipo de agrotóxico. Embora alguns estudos tenham apresentado resultados contraditórios, ser um agricultor ou morar perto de plantações ou de áreas densamente agrícolas também tem sido motivo para representar a exposição a agrotóxicos e considerado significativamente associado a um maior risco de câncer. A literatura ilustra bem o câncer de próstata, linfoma não-Hodgkin, leucemia, mieloma múltiplo, bexiga e câncer de cólon. Recomendam-se estudos que investiguem mais a relação entre agrotóxicos e neoplasmas de testículos, mama, esôfago, rim, tireoide, lábio, cabeça e pescoço e osso.

PALAVRAS-CHAVE
Câncer; Agroquímicos; Doenças profissionais; Revisão

Introduction

Pesticides are chemical substances or mixture of substances also used in the public health domain so to combat disease vectors, such as mosquitoes, as in agriculture to combat pests that harm crops¹1 World Health Organization. Pesticides [internet]. Genebra: WHO; 2019 [accessed 2017 Sept 10]. Available at: http://www.who.int/topics/pesticides/en/.
http://www.who.int/topics/pesticides/en/... . Although they form the base of modern agriculture, pesticides are associated with chemical contamination, which is a complex public and environmental health problem, especially in the rural area²2 Garcia EG, Alves Filho JP. Aspectos de prevenção e controle de acidentes no trabalho com agrotóxicos. São Paulo: Fundacentro; 2005.^,33 Peres F. Saúde, trabalho e ambiente no meio rural brasileiro. Ciênc. Saúde Colet. 2009; 14:1995-2004..

Most sprayed pesticides reach non-target species and end up polluting air, water and soil, soon contaminating the pesticide applicators, their direct family, as well as other people living in agricultural areas, who consume foods with high concentrations of these substances⁴4 Brito PF, Gomide M, Magalhães V, et al. Familiar agriculture and pesticide exposure?: brief considerations. Cad. Saúde Colet. 2005; 13(4):887-900.

5 Pacheco MEL, Guimarães MK, Silva LR. Mesa de controvérsias sobre o impacto dos agrotóxicos na soberania e segurança alimentar e nutricional e no direito humano a alimentação adequada. Brasília, DF: CONSEA; 2014.^-66 Miller GT. Biodiversity: sustaining soils and producing food. In: Miller GT. Sustaining the Earth. 6. ed. Pacific Grove, California: Thompson Learning, Inc.; 2004. p. 211-216..

Studies have related exposure to pesticides to cancer⁷7 Weichenthal S, Moase C, Chan P. A review of pesticide exposure and cancer incidence in the agricultural health study cohort. Environ. Health Perspect. 2010; 118(8):1117-1125., a chronic disease that is one of the main causes of morbidity and mortality worldwide, with over 14 million new cases in 2012⁸8 Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [internet]. Lyon, France: International Agency for Research on Cancer; 2013. [accessed 2017 Feb 27]. Available at: http://globocan.iarc.fr.. In 2015, 8.8 million people worldwide died due to malignant neoplasms, the equivalent to one in six of all global deaths¹1 World Health Organization. Pesticides [internet]. Genebra: WHO; 2019 [accessed 2017 Sept 10]. Available at: http://www.who.int/topics/pesticides/en/.
http://www.who.int/topics/pesticides/en/... .

Many review papers, available on Medline/PubMed database under the search described below, investigated the relation between pesticide and cancer. However, they either reviewed only (a) one type of cancer, (b) one type of pesticide or chemical group, (c) one study design or research group, (d) one age range, or (e) a sole population. Therefore, the aim of this study was to conduct an integrative literature review of published studies on pesticide exposure and cancer with a focus on farmers, rural population, pesticide applicators and rural workers, considering all cancer types, agricultural pesticides, and age ranges.

Methods

Studies were retrieved from the Medline/PubMed database (https://www.ncbi.nlm.nih.gov/pubmed/advanced) using the following key words in English and Portuguese: cancer OR carcinogenic OR tumor OR cancer OR carcinogenic OR neoplasia AND pesticide OR herbicide OR insecticide OR fungicide OR organophosphate OR agrochemical OR pesticide OR herbicide OR insecticide OR fungicidal OR organofosforados OR agrotoxicos OR agroquimico AND farmers OR husbandman OR agriculturists OR agriculturalists OR agricultural OR cultivator OR applicator OR agriculture OR “rural people” OR “rural population” OR “rural areas” OR “non-urban” OR rural OR “trabalhador rural” OR agricola OR applicator OR “populacao rural” OR “areas rurais” AND cohort OR “case-control” OR “case control” OR transversal OR “medical record” OR “ecological design” OR “ecologic design” OR “ecologic study” OR coorte OR “caso-controle” OR “caso controle” OR prontuario OR “delineamento ecologico”.

Original articles published between August 2007 and August 2017 and examining the relationship between pesticides and cancer were included in this review. Studies were excluded whenever they (a) were not related to farmers, rural population, agricultural pesticide applicators, rural workers, or to residents of areas with intensive use of agricultural pesticides; (b) did not analyze cancer or pesticide; (c) were reviews; (d) analyzed pesticide intake through food; (e) focused on analyses of biomarkers or dust; (f) concerned genetic studies; (g) were not written in English or Portuguese; or (h) had a focus on methodology or protocol.

A primary screening of the titles and abstracts was carried out in order to remove records that fit the excluding criteria. A second and deeper screening analyzed the full text. After the evaluation, 74 studies were chosen to compose the accepted sample (figure 1). The discussion was organized according to overall cancers and specific cancer types so as to better investigate the relationship with pesticide exposure.

Results

The search on Medline/PubMed database resulted in 167 papers, of which 74 were selected for this study (chart 1). Findings were summarized according to individual cancer types. Several specific pesticides were related to increased risk of cancer and are listed in chart 2. The vast majority of the papers reviewed concerned to either case-control (39) or cohort (32) studies. Only one study applied a cross-sectional design and two others, an ecological outline. Overall, 64 papers observed a relationship between pesticides and cancer while 10 could not find any significant positive association. Chart 3 shows the registration status of pesticides in the European Union, the United States, and Brazil.

Discussion

From the 53 pesticides listed in chart 2 relating to at least one type of cancer, most are still being used in the United States (44) and Brazil (34) (chart 3). From this list, only 8 pesticides are currently not approved nor registered, banned or severely restricted in the United States, the European Union, and Brazil: 2,4,5-T, 3,5-dinitro-o-cresol, aldrin, azinphos-methyl, carbofuran, DDT, lindane, and parathion. The pesticides mostly related to cancers fell into the category of the herbicides (24), insecticides (19), and fungicides (9) (chart 2). The most frequent chemical groups associated with cancers included organophosphates, pyrethroids, organochlorines, and thiocarbamates (chart 2).

Results from the Agricultural Health Study (AHS), a prospective cohort of licensed pesticide applicators from Iowa and North Carolina (USA), indicated that the highest levels of EPTC⁹9 Van Bemmel DM, Visvanathan K, Beane Freeman LE, et al. S-ethyl-N,N-dipropylthiocarbamate exposure and cancer incidence among male pesticide applicators in the agricultural health study: A prospective cohort. Environ Health Perspect. 2008; 116(11):1541-1546. and butylate¹⁰10 Lynch SM, Mahajan R, Beane Freeman LE, et al. Cancer incidence among pesticide applicators exposed to butylate in the Agricultural Health Study (AHS). Environ Res. 2009; 109(7):860-868. lifetime exposure days (LD) were associated to all cancers. Additionally, moderate and high exposures to terbufos also increased overall cancer hazard ratio¹¹11 Bonner MR, Williams BA, Rusiecki JA, et al. Occupational Exposure to Terbufos and the Incidence of Cancer in the Agricultural Health Study. Cancer Causes Control. 2010; 21(6):871-877.. On the other hand, some cohort studies investigated specific pesticides such as chlorothalonil¹²12 Mozzachio AM, Rusiecki JA, Hoppin JA, et al. Chlorothalonil exposure and cancer incidence among pesticide applicator participants in the agricultural health study. Environ Res. 2008; 108(3):400-403., captan¹³13 Greenburg DL, Rusiecki J, Koutros S, et al. Cancer incidence among pesticide applicators exposed to captan in the Agricultural Health Study. Cancer Causes Control. 2008; 19(10):1401-1407., malathion¹⁴14 Bonner MR, Coble J, Blair A, et al. Malathion exposure and the incidence of cancer in the agricultural health study. Am J Epidemiol. 2007; 166(9):1023-1034., and dichlorvos¹⁵15 Koutros S, Mahajan R, Zheng T, et al. Dichlorvos Exposure and Human Cancer Risk: Results from the Agricultural Health Study. Cancer Causes Control. 2008; 19(1):59-65., although not finding any association with cancer.

To reside near crops was reported to increase cancer risk in children younger than 14¹⁶16 Gómez-Barroso D, García-Pérez J, López-Abente G, et al. Agricultural crop exposure and risk of childhood cancer: new findings from a case-control study in Spain. Int J Health Geogr. 2016; 15(1):18. or 15 years old¹⁷17 Carozza SE, Li B, Elgethun K, et al. Risk of childhood cancers associated with residence in agriculturally intense areas in the United States. Environ Health Perspect. 2008; 116(4):559-565.. However, another study¹⁸18 Carozza SE, Li B, Wang Q, et al. Agricultural pesticides and risk of childhood cancers. Int J Hyg Environ Health. 2009; 212(2):186-195. evaluated several types of childhood cancers and was not able to find any significant association with residence near agricultural fields.

Being a farmer also significantly increased overall cancer risk (OR=1.459, 95% CI: 1.229-1.731) when compared to non-farmers of the same gender and age range¹⁹19 Salerno C, Carcagnì A, Sacco S, et al. An Italian population-based case-control study on the association between farming and cancer: are pesticides a plausible risk factor? Arch Environ Occup Heal. 2016; 71(3):147-156.. Lemarchand et al.²⁰20 Lemarchand C, Tual S, Levêque-Morlais N, et al. Cancer incidence in the AGRICAN cohort study (2005-2011). Cancer Epidemiol. 2017; 49:175-185. also observed significantly higher overall cancer risk among male farm workers, measured by the Standardized Incidence Ratio (SIR) of 1.07, 95% CI: 1.03-1.12.

Several studies analyzed neoplasms of the hematopoietic and lymphoid tissues (LHC) and found significantly increased risk in people living in a farm²¹21 Jones RR, DellaValle CT, Flory AR, et al. Accuracy of residential geocoding in the Agricultural Health Study. Int. j. health geogr. 2014; 13(37):1-9. or near crops¹⁶16 Gómez-Barroso D, García-Pérez J, López-Abente G, et al. Agricultural crop exposure and risk of childhood cancer: new findings from a case-control study in Spain. Int J Health Geogr. 2016; 15(1):18. exposed to pesticides²²22 Delancey JOL, Alavanja MCR, Coble J, et al. Occupational Exposure to Metribuzin and the Incidence of Cancer in the Agricultural Health Study. Ann. epidemiol. 2009; 19(6):388-395.

23 Kokouva M, Bitsolas N, Hadjigeorgiou GM, et al. Pesticide exposure and lymphohaematopoietic cancers: a case-control study in an agricultural region (Larissa, Thessaly, Greece). BMC public health. 2011; 11(1):1-5.^-2424 Schinasi LH, De Roos AJ, Ray RM, et al. Insecticide exposure and farm history in relation to risk of lymphomas and leukemias in the Women's Health Initiative observational study cohort. Ann. epidemiol. 2015; 25(11):803-810., butylate herbicide¹⁰10 Lynch SM, Mahajan R, Beane Freeman LE, et al. Cancer incidence among pesticide applicators exposed to butylate in the Agricultural Health Study (AHS). Environ Res. 2009; 109(7):860-868., metribuzin herbicide²²22 Delancey JOL, Alavanja MCR, Coble J, et al. Occupational Exposure to Metribuzin and the Incidence of Cancer in the Agricultural Health Study. Ann. epidemiol. 2009; 19(6):388-395., or terbufos insecticide¹¹11 Bonner MR, Williams BA, Rusiecki JA, et al. Occupational Exposure to Terbufos and the Incidence of Cancer in the Agricultural Health Study. Cancer Causes Control. 2010; 21(6):871-877..

Leukemia primarily affects children. Several studies found association between different types of childhood leukemia and pesticide exposure²⁵25 Rull RP, Gunier R, Von Behren J, et al. Residential proximity to agricultural pesticide applications and childhood acute lymphoblastic leukemia. Environ Res. 2009; 109(7):891-899.

26 Ferreira JD, Couto AC, Pombo-de-Oliveira MS, et al. In utero pesticide exposure and leukemia in Brazilian children <2 years of age. Environ. health perspect. 2013; 121(2):269-275.^-2727 Kumar A, Vashist M, Rathee R. Maternal factors and risk of childhood leukemia. Asian pac. j. cancer prev. 2014; 15(2):781-784.. Residing near certain crops²⁸28 Booth BJ, Ward MH, Turyk ME, et al. Agricultural crop density and risk of childhood cancer in the midwestern United States: an ecologic study. Environ Heal. 2015; 14(82):1-11., or in counties of high level of agricultural activity¹⁷17 Carozza SE, Li B, Elgethun K, et al. Risk of childhood cancers associated with residence in agriculturally intense areas in the United States. Environ Health Perspect. 2008; 116(4):559-565., was also found to significantly increase the risk of childhood cancer. Although Malagoli et al.²⁹29 Malagoli C, Costanzini S, Heck JE, et al. Passive exposure to agricultural pesticides and risk of childhood leukemia in an Italian community. Int. j. hyg. environ. health. 2016; 219(8):742-748. could not find statistically significant results, they suggested that childhood leukemia risk increased when the child resides near arable crops. Children who were born in rural areas (RR= 1.43, 95% CI: 1.09-1.86, p-trend= 0.003) or in counties with the highest farming index (RR= 1.33, 95% CI: 1.04-1.69) or pesticide exposure index (RR= 1.30, 95% CI: 1.02-1.66) faced significantly higher risk to die from leukemia³⁰30 Cha ES, Hwang S, Lee WJ. Childhood leukemia mortality and farming exposure in South Korea: A national population-based birth cohort study. Cancer epidemiol. 2014; 38(4):401-407.. In adults, increased leukemia risk was significantly associated with exposure to EPTC herbicide⁹9 Van Bemmel DM, Visvanathan K, Beane Freeman LE, et al. S-ethyl-N,N-dipropylthiocarbamate exposure and cancer incidence among male pesticide applicators in the agricultural health study: A prospective cohort. Environ Health Perspect. 2008; 116(11):1541-1546. and terbufos insecticide¹¹11 Bonner MR, Williams BA, Rusiecki JA, et al. Occupational Exposure to Terbufos and the Incidence of Cancer in the Agricultural Health Study. Cancer Causes Control. 2010; 21(6):871-877.. Other risk factors related to a farm life such as living on a farm, planting crops, raising livestock or animals, working as farm workers or in the agricultural industry, and exposures to insecticides or fertilizers³¹31 Wong O, Harris F, Yiying W, et al. A hospital-based case-control study of acute myeloid leukemia in Shanghai: Analysis of personal characteristics, lifestyle and environmental risk factors by subtypes of the WHO classification. Regul. Toxiol. pharmacol. 2009; 55(3):340-352..

Hodgkin Lymphoma (HL) in males of 19 years of age or older was significantly associated with exposure to the organophosphate insecticide chlorpyrifos³²32 Karunanayake CP, Spinelli JJ, McLaughlin JR, et al. Hodgkin Lymphoma and Pesticides Exposure in Men: A Canadian Case-Control Study. J Agromedicine. 2012; 17(1):30-39. and the herbicide dichlorprop³³33 Pahwa P, Karunanayake CP, Spinelli JJ, et al. Ethnicity and incidence of Hodgkin lymphoma in Canadian population. BMC cancer. 2009; 9(141):1-9.. Hodgkin’s disease and Non-Hodgkin Lymphoma (NHL) were significantly reduced in districts with low pesticides exposure compared to those with high exposure³⁴34 Parrón T, Requena M, Hernández AF, et al. Environmental exposure to pesticides and cancer risk in multiple human organ systems. Toxicol. lett. 2014; 230(2):157-165..

Non-Hodgkin lymphoma risk factors include: being an agricultural worker³⁵35 Richardson DB, Terschüren C, Hoffmann W. Occupational Risk Factors for Non-Hodgkin's Lymphoma?: A Population-Based Case - Control Study in Northern Germany. Am J Ind Med. 2008; 51:258-268.

36 Boccolini PMM, Boccolini CS, Chrisman JR, et al. Non-Hodgkin lymphoma among Brazilian agricultural workers: A death certificate case-control study. Environ Occup Heal. 2016; 72(3):139-144.^-3737 Kachuri L, Harris MA, MacLeod JS, et al. Cancer risks in a population-based study of 70,570 agricultural workers: results from the Canadian census health and Environment cohort (CanCHEC). BMC cancer. 2017; 17(343):1-15. or a farmer³⁵35 Richardson DB, Terschüren C, Hoffmann W. Occupational Risk Factors for Non-Hodgkin's Lymphoma?: A Population-Based Case - Control Study in Northern Germany. Am J Ind Med. 2008; 51:258-268.^,3838 Wong O, Harris F, Armstrong TW, et al. A hospital-based case-control study of non-Hodgkin lymphoid neoplasms in Shanghai: Analysis of environmental and occupational risk factors by subtypes of the WHO classification. Chem. Boil. interact. 2010; 184(1-2):129-146.^,3939 Karunanayake CP, Dosman JA, Pahwa P. Non-hodgkin's lymphoma and work in agriculture: Results of a two case-control studies in Saskatchewan, Canada. Indian j. occup. environ. med. 2013; 17(3):114-121.; living in a farm or in communities between 1,000 and 10,000 people³⁹39 Karunanayake CP, Dosman JA, Pahwa P. Non-hodgkin's lymphoma and work in agriculture: Results of a two case-control studies in Saskatchewan, Canada. Indian j. occup. environ. med. 2013; 17(3):114-121.; being exposed to pesticides³⁹39 Karunanayake CP, Dosman JA, Pahwa P. Non-hodgkin's lymphoma and work in agriculture: Results of a two case-control studies in Saskatchewan, Canada. Indian j. occup. environ. med. 2013; 17(3):114-121., potentially carcinogenic pesticides⁴⁰40 Hohenadel K, Harris SA, McLaughlin JR, et al. Exposure to multiple pesticides and risk of non-Hodgkin lymphoma in men from six Canadian provinces. Int. j. environ. res. public health. 2011; 8(6):2320-2330., herbicides³⁵35 Richardson DB, Terschüren C, Hoffmann W. Occupational Risk Factors for Non-Hodgkin's Lymphoma?: A Population-Based Case - Control Study in Northern Germany. Am J Ind Med. 2008; 51:258-268.^,3838 Wong O, Harris F, Armstrong TW, et al. A hospital-based case-control study of non-Hodgkin lymphoid neoplasms in Shanghai: Analysis of environmental and occupational risk factors by subtypes of the WHO classification. Chem. Boil. interact. 2010; 184(1-2):129-146.^,4040 Hohenadel K, Harris SA, McLaughlin JR, et al. Exposure to multiple pesticides and risk of non-Hodgkin lymphoma in men from six Canadian provinces. Int. j. environ. res. public health. 2011; 8(6):2320-2330., insecticides³⁸38 Wong O, Harris F, Armstrong TW, et al. A hospital-based case-control study of non-Hodgkin lymphoid neoplasms in Shanghai: Analysis of environmental and occupational risk factors by subtypes of the WHO classification. Chem. Boil. interact. 2010; 184(1-2):129-146.^,4040 Hohenadel K, Harris SA, McLaughlin JR, et al. Exposure to multiple pesticides and risk of non-Hodgkin lymphoma in men from six Canadian provinces. Int. j. environ. res. public health. 2011; 8(6):2320-2330., or fungicides^(40.) Some specific insecticides such as DDT⁴¹41 Alavanja MCR, Hofmann JN, Lynch CF, et al. Non-Hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the agricultural health study. PLoS One. 2014; 9(10):1-17., lindane⁴¹41 Alavanja MCR, Hofmann JN, Lynch CF, et al. Non-Hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the agricultural health study. PLoS One. 2014; 9(10):1-17., and terbufos¹¹11 Bonner MR, Williams BA, Rusiecki JA, et al. Occupational Exposure to Terbufos and the Incidence of Cancer in the Agricultural Health Study. Cancer Causes Control. 2010; 21(6):871-877.^,4141 Alavanja MCR, Hofmann JN, Lynch CF, et al. Non-Hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the agricultural health study. PLoS One. 2014; 9(10):1-17., as well as some specific herbicides such as butylate¹⁰10 Lynch SM, Mahajan R, Beane Freeman LE, et al. Cancer incidence among pesticide applicators exposed to butylate in the Agricultural Health Study (AHS). Environ Res. 2009; 109(7):860-868. and paraquat⁴²42 Park SK, Kang D, Beane-freeman L, et al. Cancer incidence among paraquat-exposed pesticide applicators in the Agricultural Health Study. Int J Occup Env Heal. 2009; 15(3):274-281., were also associated with higher risk of NHL.

Multiple myeloma was associated to six specific types of pesticides. Otherwise, results were contradictory for captan fungicide and carbaryl insecticide. While three case-control studies⁴³43 Kachuri L, Demers PA, Blair A, et al. Multiple pesticide exposures and the risk of multiple myeloma in Canadian men. Int. j. cancer. 2013; 133(8):1846-1858.

44 Pahwa P, Karunanayake CP, Dosman JA, et al. Multiple Myeloma and Exposure to Pesticides: A Canadian Case-Control Study. J Agromedicine. 2012; 17(1):40-50.^-4545 Presutti R, Harris SA, Kachuri L, et al. Pesticide exposures and the risk of multiple myeloma in men: an analysis of the North American Pooled Project (NAPP). Int. j. cancer. 2016; 139(8):1703-1714. showed that these pesticides increased MM risk, one cohort study⁴¹41 Alavanja MCR, Hofmann JN, Lynch CF, et al. Non-Hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the agricultural health study. PLoS One. 2014; 9(10):1-17. could not find significant associations. Different results also appeared for DDT and lindane insecticides. Presutti et al.⁴⁵45 Presutti R, Harris SA, Kachuri L, et al. Pesticide exposures and the risk of multiple myeloma in men: an analysis of the North American Pooled Project (NAPP). Int. j. cancer. 2016; 139(8):1703-1714. found DDT to be linked to MM, but could not trace significant correlation between lindane and MM. Conversely, Kachuri et al.⁴³43 Kachuri L, Demers PA, Blair A, et al. Multiple pesticide exposures and the risk of multiple myeloma in Canadian men. Int. j. cancer. 2013; 133(8):1846-1858. and Pahwa et al.⁴⁴44 Pahwa P, Karunanayake CP, Dosman JA, et al. Multiple Myeloma and Exposure to Pesticides: A Canadian Case-Control Study. J Agromedicine. 2012; 17(1):40-50. found DDT not to be linked to MM, while lindane showed a significant association. Two cohort studies investigated permethrin insecticide⁴¹41 Alavanja MCR, Hofmann JN, Lynch CF, et al. Non-Hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the agricultural health study. PLoS One. 2014; 9(10):1-17.^,4646 Rusiecki JA, Patel R, Koutros S, et al. Cancer incidence among pesticide applicators exposed to permethrin in the Agricultural Health Study. Environ. health perspect. 2009; 117(4):581-586., and other two case-control studies⁴³43 Kachuri L, Demers PA, Blair A, et al. Multiple pesticide exposures and the risk of multiple myeloma in Canadian men. Int. j. cancer. 2013; 133(8):1846-1858.^,4444 Pahwa P, Karunanayake CP, Dosman JA, et al. Multiple Myeloma and Exposure to Pesticides: A Canadian Case-Control Study. J Agromedicine. 2012; 17(1):40-50. investigated mecoprop herbicide, and they all found significant high MM risk. Consistency was also seen among the four studies about not finding significant associations between malathion and MM⁴¹41 Alavanja MCR, Hofmann JN, Lynch CF, et al. Non-Hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the agricultural health study. PLoS One. 2014; 9(10):1-17.^,4343 Kachuri L, Demers PA, Blair A, et al. Multiple pesticide exposures and the risk of multiple myeloma in Canadian men. Int. j. cancer. 2013; 133(8):1846-1858.

44 Pahwa P, Karunanayake CP, Dosman JA, et al. Multiple Myeloma and Exposure to Pesticides: A Canadian Case-Control Study. J Agromedicine. 2012; 17(1):40-50.^-4545 Presutti R, Harris SA, Kachuri L, et al. Pesticide exposures and the risk of multiple myeloma in men: an analysis of the North American Pooled Project (NAPP). Int. j. cancer. 2016; 139(8):1703-1714.. Furthermore, increased risk of MM was seen among men who reported the use of fungicides, pesticides classified as probably carcinogenic or higher, using at least one carbamate pesticide, one phenoxy herbicide, and ³3 Peres F. Saúde, trabalho e ambiente no meio rural brasileiro. Ciênc. Saúde Colet. 2009; 14:1995-2004. organochlorines⁴³43 Kachuri L, Demers PA, Blair A, et al. Multiple pesticide exposures and the risk of multiple myeloma in Canadian men. Int. j. cancer. 2013; 133(8):1846-1858.. Occasional, although intense, use of pesticides or herbicides by men also caused a significant MM excess risk (RR=1.20, 95% CI: 1.07-1.34)⁴⁷47 Lope V, Pérez-Gómez B, Aragonés N, et al. Occupation, exposure to chemicals, sensitizing agents, and risk of multiple myeloma in Sweden. Cancer epidemiol. biomark. prev. 2008; 17(11):3123-3127.. Female crop farmers³⁷37 Kachuri L, Harris MA, MacLeod JS, et al. Cancer risks in a population-based study of 70,570 agricultural workers: results from the Canadian census health and Environment cohort (CanCHEC). BMC cancer. 2017; 17(343):1-15., as well as female and male pesticide users⁴⁸48 Frost G, Brown T, Harding AH. Mortality and cancer incidence among British agricultural pesticide users. Occup Med (Lond). 2011; 61(5):303-310., suffered higher incidences of MM. Similarly, a study²⁰20 Lemarchand C, Tual S, Levêque-Morlais N, et al. Cancer incidence in the AGRICAN cohort study (2005-2011). Cancer Epidemiol. 2017; 49:175-185. observed higher risks among males and females who work in farms and among male farm owners (SIR=1.59 95% CI: 1.29-1.95) and male users of pesticides on crops (SIR=1.49, 95% CI: 1.19-1.84).

Although the main risk factors, i.e., age, black race, family history, related to prostate neoplasm are already identified, this integrative review revealed that exposure to butylate¹⁰10 Lynch SM, Mahajan R, Beane Freeman LE, et al. Cancer incidence among pesticide applicators exposed to butylate in the Agricultural Health Study (AHS). Environ Res. 2009; 109(7):860-868., methyl bromide⁴⁹49 Cockburn M, Mills P, Zhang X, et al. Prostate cancer and ambient pesticide exposure in agriculturally intensive areas in California. Am j. epidemiol. 2011; 173(11):1280-1288., a group of organochlorine insecticide⁴⁹49 Cockburn M, Mills P, Zhang X, et al. Prostate cancer and ambient pesticide exposure in agriculturally intensive areas in California. Am j. epidemiol. 2011; 173(11):1280-1288., and terbufos¹¹11 Bonner MR, Williams BA, Rusiecki JA, et al. Occupational Exposure to Terbufos and the Incidence of Cancer in the Agricultural Health Study. Cancer Causes Control. 2010; 21(6):871-877. were found to increase the risk. High exposure to the (i) insecticides DDT, lindane, 3,5-dinitro-cresol, azinphos-methyl, carbaryl, diazinon, malathion, (ii) herbicides 2,4-DB, MCPA, simazine, and (iii) fungicides copper sulfate, dichlone, ferbam, maneb, sulfur, ziram significantly increased prostate cancer risk in males⁵⁰50 Band PR, Abanto Z, Bert J, et al. Prostate cancer risk and exposure to pesticides in British Columbia Farmers. Prostate. 2011; 71(2):168-183.^,5151 Sharma M, Lawson JA, Kanthan R, et al. Factors Associated With the Prevalence of Prostate Cancer in Rural Saskatchewan: The Saskatchewan Rural Health Study. J Rural Heal. 2016; 32(2):125-135.. Prostate cancer risk was higher among male agricultural workers²⁰20 Lemarchand C, Tual S, Levêque-Morlais N, et al. Cancer incidence in the AGRICAN cohort study (2005-2011). Cancer Epidemiol. 2017; 49:175-185.^,3737 Kachuri L, Harris MA, MacLeod JS, et al. Cancer risks in a population-based study of 70,570 agricultural workers: results from the Canadian census health and Environment cohort (CanCHEC). BMC cancer. 2017; 17(343):1-15. and men exposed to coumaphos who reported a family history of that cancer⁵²52 Christensen CH, Platz EA, Andreotti G, et al. Coumaphos exposure and incident cancer among male participants in the Agricultural Health Study (AHS). Environ. health perspect. 2010; 118(1):92-96..

Primary testicular tumors are the most common solid malignant tumor in men aged 20 to 34 years in the United States⁵³53 United States. National Cancer Institute. Cancer Stat Facts: Testicular Cancer [internet].Maryland: National Cancer Institute; 2019. [accessed 2018 Dec 30]. Available at: https://seer.cancer.gov/statfacts/html/testis.html. and its cause is still unknown, although a study has evidenced that its incidence was significantly higher among male pesticide users (SIR=1.26, 95% CI: 1.04-1.53)⁴⁸48 Frost G, Brown T, Harding AH. Mortality and cancer incidence among British agricultural pesticide users. Occup Med (Lond). 2011; 61(5):303-310..

Among malignant neoplasms of digestive organs, the herbicides EPTC and pendimethalin were associated with pancreatic cancer among pesticide applicators and their spouses³⁷37 Kachuri L, Harris MA, MacLeod JS, et al. Cancer risks in a population-based study of 70,570 agricultural workers: results from the Canadian census health and Environment cohort (CanCHEC). BMC cancer. 2017; 17(343):1-15.^,5454 Andreotti G, Freeman LEB, Hou L, et al. Agricultural Pesticide Use and Pancreatic Cancer Risk in the Agricultural Health Study Cohort Gabriella. Int. j. cancer. 2009; 124(10):2495-2500.. Stomach cancer risk significantly increased with exposure to methyl bromide⁵⁵55 Barry KH, Koutros S, Lubin JH, et al. Methyl bromide exposure and cancer risk in the Agricultural Health Study. Cancer causes control. 2012; 23(6):807-818. and in districts with greater pesticide use³⁴34 Parrón T, Requena M, Hernández AF, et al. Environmental exposure to pesticides and cancer risk in multiple human organ systems. Toxicol. lett. 2014; 230(2):157-165.. Colorectal cancer risk was significantly higher among farmers (OR=1.529, 95% CI: 1.011-2.314)¹⁹19 Salerno C, Carcagnì A, Sacco S, et al. An Italian population-based case-control study on the association between farming and cancer: are pesticides a plausible risk factor? Arch Environ Occup Heal. 2016; 71(3):147-156., those exposed to pesticide (OR=2.6, 95% CI: 1.1-5.9), and those primarily sourcing food directly from farms (OR=4.6, 95% CI: 1.5-14.6)⁵⁶56 Lo A-C, Soliman AS, Khaled HM, et al. Lifestyle, occupational, and reproductive factors and risk of colorectar cancer. Dis. colon rectum. 2010; 53(5):830-837.. A higher prevalence of colon cancer was also observed among male pesticide applicators exposed to EPTC⁹9 Van Bemmel DM, Visvanathan K, Beane Freeman LE, et al. S-ethyl-N,N-dipropylthiocarbamate exposure and cancer incidence among male pesticide applicators in the agricultural health study: A prospective cohort. Environ Health Perspect. 2008; 116(11):1541-1546., trifluralin⁵⁷57 Kang D, Park SK, Beane-Freeman L, et al. Cancer incidence among pesticide applicators exposed to trifluralin in the Agricultural Health Study. Environ. res. 2008; 107(2):271-276., carbofuran, metolachlor, and alachlor⁵⁸58 Andreotti G, Hou L, Freeman LEB, et al. Body Mass Index, Agricultural Pesticide Use, and Cancer Incidence in the Agricultural Health Study Cohort. Cancer causes control. 2010; 21(11):1759-1775.. Esophagus cancer deaths were, in general, significantly higher (OR=1.38, 95% CI: 1.26-1.51) among agricultural than among non-agricultural workers in the south region of Brazil, an area with intense pesticide use⁵⁹59 Meyer A, Alexandre PCB, Chrisman JR, et al. Esophageal cancer among Brazilian agricultural workers: Case-control study based on death certificates. Int. j. hyg. environ. health. 2011; 214(2):151-155.. The Hepatocellular Carcinoma (HCC) can be affected by several factors, and pesticide exposure may contribute to non-B and non-C HCC in areas with high level of agricultural activity¹⁷17 Carozza SE, Li B, Elgethun K, et al. Risk of childhood cancers associated with residence in agriculturally intense areas in the United States. Environ Health Perspect. 2008; 116(4):559-565.^,3434 Parrón T, Requena M, Hernández AF, et al. Environmental exposure to pesticides and cancer risk in multiple human organ systems. Toxicol. lett. 2014; 230(2):157-165.^,6060 Azm ARAE, Yousef M, Mansour N, et al. New insights on non-B non-C hepatocellular carcinoma in mid Delta Region, Egypt. J gastrointest cancer. 2014; 45(3):276-283.

61 VoPham T, Brooks MM, Yuan JM, et al. Pesticide exposure and hepatocellular carcinoma risk: A case-control study using a geographic information system (GIS) to link SEER-Medicare and California pesticide data. Environ. res. 2015; 143:68-82.^-6262 Silver SR, Bertke SJ, Hines CJ, et al. Cancer incidence and metolachlor use in the Agricultural Health Study: An update. Int. j. cancer. 2015; 137(11):2630-2643.. In contrast, Jeephet et al.⁶³63 Jeephet K, Kamsa-Ard S, Bhudhisawasdi V, et al. Association between pesticide use and cholangiocarcinoma. Asian pac. J. cancer prev. 2016; 17(8):3977-3980. were not able to find statistically significant association between pesticide use and cholangio carcinoma.

Central nervous system tumors increased among farmers (HR= 1.73, 95% CI: 1.01-2.94)⁶⁴64 Piel C, Pouchieu C, Tual S, et al. Central nervous system tumors and agricultural exposures in the prospective cohort AGRICAN. Int. j. cancer. 2017; 141(9):1771-1782., pesticide applicators (HR= 1.96; 95% CI: 1.11-3.47)⁶⁴64 Piel C, Pouchieu C, Tual S, et al. Central nervous system tumors and agricultural exposures in the prospective cohort AGRICAN. Int. j. cancer. 2017; 141(9):1771-1782., and children living in countries with high level of agricultural activity (OR= 1.3, 95% CI: 1.1-1.4)¹⁷17 Carozza SE, Li B, Elgethun K, et al. Risk of childhood cancers associated with residence in agriculturally intense areas in the United States. Environ Health Perspect. 2008; 116(4):559-565.. Brain cancer prevalence³⁴34 Parrón T, Requena M, Hernández AF, et al. Environmental exposure to pesticides and cancer risk in multiple human organ systems. Toxicol. lett. 2014; 230(2):157-165. and its mortality⁶⁵65 Miranda Filho AL, Monteiro GTR, Meyer A. Brain cancer mortality among farm workers of the State of Rio de Janeiro, Brazil: A population-based case-control study, 1996-2005. Int. j. hyg. environ. health. 2012; 215(5):496-501.^,6666 Miranda Filho AL, Koifman RJ, Koifman S, et al. Brain cancer mortality in an agricultural and a metropolitan region of Rio de Janeiro, Brazil: a population-based, age-period-cohort study, 1996-2010. BMC cancer. 2014; 14(320):1-9. showed significantly higher rates in districts with greater pesticide use. Glioma was associated with never changing clothes (OR=2.84, 95% CI: 1.04-7.78) or never washing face and hands (OR=3.08, 95% CI: 1.78-5.34) immediately after applying pesticides⁶⁷67 Ruder AM, Carreón T, Butler MA, et al. Exposure to farm crops, livestock, and farm tasks and risk of glioma. Am. j. epidemiol. 2009; 169(12):1479-1491.. Controversially, a study investigating pesticide applicators did not find any positive association between glioma and farm pesticide use⁶⁸68 Yiin JH, Ruder AM, Stewart PA, et al. The upper midwest health study: a case-control study of pesticide applicators and risk of glioma. Environ Heal. 2012; 11(39):1-13..

As for malignant neoplasms of female genital organs, a study⁶⁹69 Zhang B, Zhou AF, Zhu C-C, et al. Risk Factors for Cervical Cancer in Rural Areas of Wuhan China: a Matched Case-control Study. Asian pac. j. cancer prev. 2013; 14(12):7595-7600. investigated risk factors for cervical cancer and could not find any association with insecticides. The result was anticipated, once most cervical cancer cases are caused by the human papillomavirus, a well-known risk factor. Ashley-Martin et al.⁷⁰70 Ashley-Martin J, Vanleeuwen J, Cribb A. Breast cancer risk, fungicide exposure and cyp1a1*2a gene-environment interactions in a province-wide case control study in prince edward island, Canada. Int. j. environ. res. public health. 2012; 9(5):1846-1858. did not find significant associations between breast cancer and fungicide exposure. However, Salerno et al.¹⁹19 Salerno C, Carcagnì A, Sacco S, et al. An Italian population-based case-control study on the association between farming and cancer: are pesticides a plausible risk factor? Arch Environ Occup Heal. 2016; 71(3):147-156. observed that farmers were at significantly higher risk for breast cancer (OR=1.720, 95% CI: 1.039-2.846), and Lerro et al.⁷¹71 Lerro CC, Koutros S, Andreotti G, et al. Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study. Occup Environ Med. 2015; 72(10):736-744. found organophosphate insecticides to be associated with breast tumor and diazinon to significantly increase the risk of ovarian cancer.

Among malignant neoplasms of urinary tract, bladder cancer revealed to be the most common type associated with pesticides. The prevalence was significantly higher in districts with greater pesticide use³⁴34 Parrón T, Requena M, Hernández AF, et al. Environmental exposure to pesticides and cancer risk in multiple human organ systems. Toxicol. lett. 2014; 230(2):157-165.. Any use of imazethapyr, imazaquin, bentazon, bromoxynil, chloramben, and diclofop-methyl herbicides increased the risk of bladder cancer, as did the insecticide DDT solely⁷²72 Koutros S, Lynch CF, Ma X, et al. Aromatic amine pesticide use and human cancer risk: results from the U.S. Agricultural Health Study. Int J Cancer. 2009; 124(5):1206-1212.^,7373 Koutros S, Silverman DT, Alavanja MCR, et al. Occupational exposure to pesticides and bladder cancer risk. Int J Epidemiol. 2016; 45(3):792-805.. In contrast, a study⁷⁴74 Boulanger M, Tual S, Lemarchand C, et al. Agricultural exposure and risk of bladder cancer in the AGRIculture and CANcer cohort. Int Arch Occup Environ Heal. 2017; 90(2):169-178. investigating risk factors for bladder cancer among farm workers could not find any significant increasing risk for pesticide exposure, whilst significant high risk was observed among field-grown vegetable workers. Renal tumors were associated with living in counties with high level of agricultural activity (OR=2.1, 95% CI: 1.7-2.6)¹⁷17 Carozza SE, Li B, Elgethun K, et al. Risk of childhood cancers associated with residence in agriculturally intense areas in the United States. Environ Health Perspect. 2008; 116(4):559-565..

Lung cancer is the primary contributor of malignant neoplasms of respiratory and intrathoracic organs. After controlling for several factors including smoking, which is the most common risk factor, lung cancer among pesticide applicators from the AHS cohort was significantly associated to high exposure to the organophosphate insecticide diazinon (RR=1.60, 95% CI: 1.11-2.31)⁷⁵75 Jones RR, Barone-Adesi F, Koutros S, et al. Incidence of solid tumours among pesticide applicators exposed to the organophosphate insecticide diazinon in the Agricultural Health Study: an updated analysis. Occup. Environ. med. 2015; 72(7):1-18.. The highest quartile of use of the herbicide chlorimuron ethyl showed high risk of lung cancer⁷⁶76 Bonner MR, Freeman LEB, Hoppin JA, et al. Occupational Exposure to Pesticides and the Incidence of Lung Cancer in the Agricultural Health Study. Environ. health perspect. 2017; 125(4):544-551.. Significantly higher prevalence was also observed in districts with greater pesticide use³⁴34 Parrón T, Requena M, Hernández AF, et al. Environmental exposure to pesticides and cancer risk in multiple human organ systems. Toxicol. lett. 2014; 230(2):157-165..

Cutaneous melanoma incidence among pesticide applicators was significantly increased by the exposure to parathion and carbaryl insecticides and maneb/mancozeb fungicide after adjusting for risk factors⁷⁷77 Dennis LK, Lynch CF, Sandler DP, et al. Pesticide use and cutaneous melanoma in pesticide applicators in the agricultural heath study. Environ health perspect. 2010; 118(6):812-817.^,7878 Mahajan R, Blair A, Coble J, et al. Carbaryl exposure and incident cancer in the Agricultural Health Study. Int j. cancer. 2007; 121(8):1799-1805.. A higher risk for skin melanoma (SIR= 1.30, 95% CI: 1.00-1.66) was observed among female farm workers²⁰20 Lemarchand C, Tual S, Levêque-Morlais N, et al. Cancer incidence in the AGRICAN cohort study (2005-2011). Cancer Epidemiol. 2017; 49:175-185.. Additionally, an increased melanoma hazard ratio among male agricultural workers and female crop farmers was also identified³⁷37 Kachuri L, Harris MA, MacLeod JS, et al. Cancer risks in a population-based study of 70,570 agricultural workers: results from the Canadian census health and Environment cohort (CanCHEC). BMC cancer. 2017; 17(343):1-15.. A study investigated uveal melanoma but could not find positive associations with activities of farming, pesticide application, or pesticide mixing⁷⁹79 Behrens T, Lynge E, Cree I, et al. Pesticide exposure in farming and forestry and the risk of uveal melanoma. Cancer causes control. 2012; 23(1):141-151..

Soft Tissue Sarcoma (STS) was significantly associated to also exposure to aldrin and diazinon among men aged 19 years or older⁸⁰80 Pahwa P, Karunanayake CP, Dosman JA, et al. Soft-Tissue Sarcoma and Pesticides Exposure in Men. J. occup environ. med. 2011; 53(11):1279-1286. as to with high level of agricultural activity (OR=1.7, 95% CI: 1.4-2.0)¹⁷17 Carozza SE, Li B, Elgethun K, et al. Risk of childhood cancers associated with residence in agriculturally intense areas in the United States. Environ Health Perspect. 2008; 116(4):559-565.. Among British women, it was observed that pesticide users died more often from STS than the national population⁴⁸48 Frost G, Brown T, Harding AH. Mortality and cancer incidence among British agricultural pesticide users. Occup Med (Lond). 2011; 61(5):303-310.. Malignant bone tumors were associated to living in counties with high level of agricultural activity (OR=2.3, 95% CI: 1.8-2.9)¹⁷17 Carozza SE, Li B, Elgethun K, et al. Risk of childhood cancers associated with residence in agriculturally intense areas in the United States. Environ Health Perspect. 2008; 116(4):559-565..

Head and neck cancer was reported among men and women residing in rural areas⁸¹81 Govett G, Genuis SJ, Govett HE, et al. Chlorinated pesticides and cancer of the head and neck. Eur. j. cancer prev. 2011; 20(4):320-325.. Thyroid cancer risk increased with malathion⁷¹71 Lerro CC, Koutros S, Andreotti G, et al. Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study. Occup Environ Med. 2015; 72(10):736-744. and atrazine exposure⁸²82 Freeman LEB, Rusiecki JA, Hoppin JA, et al. Atrazine and cancer incidence among pesticide applicators in the Agricultural Health Study (1994-2007). Environ health perspect. 2011; 119(9):1253-1259.. Lip cancer risk was significantly higher among male agricultural workers (HR= 2.14, 95% CI: 1.70-2.70)³⁷37 Kachuri L, Harris MA, MacLeod JS, et al. Cancer risks in a population-based study of 70,570 agricultural workers: results from the Canadian census health and Environment cohort (CanCHEC). BMC cancer. 2017; 17(343):1-15. and male farm workers (SIR=2.87, 95% CI: 1.61-4.74)²⁰20 Lemarchand C, Tual S, Levêque-Morlais N, et al. Cancer incidence in the AGRICAN cohort study (2005-2011). Cancer Epidemiol. 2017; 49:175-185..

Myelodysplastic Syndromes (MDS) were significantly associated to ever exposure to pesticides (OR=2.47, 95% CI: 1.44-4.24), insecticides (OR=3.34, 95% CI: 1.62-6.90) and herbicides (OR= 2.27, 95% CI: 1.14-4.51), but not to fungicides⁸³83 Avgerinou C, Giannezi I, Theodoropoulou S, et al. Occupational, dietary, and other risk factors for myelodysplastic syndromes in Western Greece. Hematology. 2017; 22(7):419-429.. Paraquat was the only specific pesticide to positively and significantly associate with MDS (OR= 4.90, 95% CI: 1.05-22.75).

The choice for an integrative review may be considered one of the strengths of this study, since it is the only approach that allows for combining results of different methodologies. This study has the potential to enable for the diversity in primary research to be summarized and to become an instrument also for medical professionals that deal with cancers as for decision-makers responsible for making the public policies, once risks to populations were identified.

As for its limitations, this study focused on a very wide topic that encompassed all kinds of pesticides and cancers, which may have led to the loss of specific details. Second, it was only able to analyze the registration status of pesticides in the United States, Brazil, and the European Union, since most of the papers retrieved from the Medline/PubMed database belonged to those places. It would certain be beneficial to further add other countries to the comparison. It is important to note that half of the studies retrieved were carried out in the USA, being 25 published by AHS researchers. Epidemiologic evidence outside the AHS cohort remains limited as far as associations observed for specific pesticides and cancer types are concerned. Third and last, this study did not discuss potential mechanisms of action of pesticides that could have improved the study.

Conclusions

This integrative literature review showed that the risk of several cancer types increased significantly with exposure to several types of pesticides, most of which are still in use in the United States and Brazil. Although a few studies presented contradictory results, being a farmer or living near crops or high agricultural areas have also been used as a proxy for pesticide exposure and significantly associated with higher cancer risk.

In general, the literature is well illustrated in the case of prostate cancer, NHL, leukemia, multiple myeloma, bladder and colon cancers. Studies that further investigate the relationship between pesticide and neoplasms of testis, breast, esophagus, kidney, thyroid, lip, head/neck, and bone are recommended. It is hoped that this study can be used as a reference material and will contribute to future research regarding pesticide exposure and cancer incidence.

References

Publication Dates

History