SciELO - Scientific Electronic Library Online

 
vol.43 issue122Experiences and Stages in the Reality of the Unified Health System Project: line of flight in health education for collective health actionCBRN events management and the use of the Hysplit model: an integrative literature review author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand

Journal

Article

Indicators

Related links

Share


Saúde em Debate

Print version ISSN 0103-1104On-line version ISSN 2358-2898

Saúde debate vol.43 no.122 Rio de Janeiro July/Sept. 2019  Epub Nov 25, 2019

https://doi.org/10.1590/0103-1104201912220 

REVIEW

Pesticide exposure and cancer: an integrative literature review

Exposição a agrotóxicos e câncer: uma revisão integrativa da literatura

Thaís Bremm Pluth1 
http://orcid.org/0000-0002-5851-9476

Lucas Adalberto Geraldi Zanini2  3 
http://orcid.org/0000-0002-3849-6211

Iara Denise Endruweit Battisti1 
http://orcid.org/0000-0001-9740-4199

1Universidade Federal da Fronteira Sul (UFFS) - Cerro Largo (RS), Brazil. thaisbremm@hotmail.com

2Hospital de Caridade de Ijuí (HCI) - Ijuí (RS), Brazil.

3Universidade Regional do Noroeste do Estado do Rio Grande do Sul (Unijuí)- Ijuí (RS), Brazil.


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 crops1. 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 area2,3.

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 substances4-6.

Studies have related exposure to pesticides to cancer7, a chronic disease that is one of the main causes of morbidity and mortality worldwide, with over 14 million new cases in 20128. In 2015, 8.8 million people worldwide died due to malignant neoplasms, the equivalent to one in six of all global deaths1.

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.

Source: Own elaboration.

Figure 1 Flowchart of the studies included in this integrative review 

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.

Chart 1 Summary of studies selected for this review 

Cancer type Study design Sample size Place/Country of study References
Bladder and colon Cohort 20,646 IA and NC, USA Koutros et al. (2009)72
Bladder Cohort 54,344 IA and NC, USA Koutros et al. (2016)73
Bladdera Cohort 148,051 France Boulanger et al. (2017)74
Brain Case-control 2,040 cases + 4,140 controls RJ, Brazil Miranda-Filho et al. (2012)65
Brain Cohort 7,734 RJ, Brazil Miranda Filho et al. (2014)66
Breasta Case-control 207 cases + 621 controls Canada Ashley-Martin et al. (2012)70
Cervical Case-control 33 cases +132 controls Wuhan, China Zhang et al. (2013)69
Cholangio carcinomaa Case-control 210 cases + 840 controls Thailand Jeephet et al. (2016)63
CNSb Cohort 181,842 France Piel et al. (2017)64
Colon Cohort 25,712 IA and NC, USA Kang et al. (2008)57
Colon and breast Cohort 39,628 men + 28,319 women IA and NC, USA Andreotti et al. (2010)58
Colorretal Case-control 421 cases + 439 controls Egypt Lo et al. (2010)56
Cutaneous melanoma Case-control 150 cases + 24,554 controls IA and NC, USA Dennis et al. (2010)77
Esophagus Case-control 5,782 cases + 5,782 controls RS, PR, SC, Brazil Meyer et al. (2011)59
Glioma Case-control 798 cases + 1,175 controls IA, MI, MN, and WI, USA Ruder et al. (2009)67
Gliomaa Case-control 798 cases + 1,175 controls IA, MI, MN, and WI, USA Yiin et al. (2012)68
HCCc Case-control 3,034 cases + 14,991 controls CA, USA Vopham et al. (2015)61
Head and neck Case-control 7 cases + 5 controls Oklahoma, USA Govett et al. (2011)81
HLd Case-control 316 cases + 1,506 controls 6 provinces, Canada Pahwa et al. (2009)33
HLd Case-control 316 cases + 1,506 controls 6 provinces, Canada Karunanayake et al. (2012)32
Leukemia Case-control 252 cases + 423 controls 13 states, Brazil Ferreira et al. (2013)26
Leukemia Cohort 6,479,406 South Korea Cha et al. (2014)30
Leukemia Case-control 132 cases + 132 controls Rohtak, India Kumar et al. (2014)27
Leukemia Ecologic Not applicable 6 states, USA Booth et al. (2015)28
Leukemiaa Case-control 111 casos + 444 controls 2 provinces, Italy Malagoli et al. (2016)29
Leukemia (ALLe) Case-control 213 cases + 268 controls CA, USA Rull et al. (2009)25
Leukemia (AMLf) Case-control 722 cases + 1,444 controls Shanghai, China Wong et al. (2009)31
Liver Case-control 281 cases + 20 controls Tanta, Egypt Azm et al. (2014)60
Liver and follicular cell lymphoma Cohort 49,616 IA and NC, USA Silver et al. (2015)62
Lung Cohort 22,830 IA and NC, USA Jones et al. (2015)21
Lung Case-control 546 cases + 49,266 controls IA and NC, USA Bonner et al. (2017)76
LHCg Cohort 23,072 IA and NC, USA Delancey et al. (2009)22
LHCg Case-control 354 cases + 455 controls Tessalia, Greece Kokouva et al. (2011)23
LHCg Cohort 37,099 IA, USA Jones et al. (2014)21
LHCg Cohort 76,493 USA Schinasi et al. (2015)24
Melanoma Cohort 21,416 IA and NC, USA Mahajan et al. (2007)78
MDSh Case-control 126 cases + 102 controls Greece Avgerinou et al. (2017)83
MMi Cohort 2,992,166 Sweden Lope et al. (2008)47
MMi Cohort 49,093 IA and NC, USA Rusiecki et al. (2009)46
MMi Case-control 342 cases + 1,506 controls 6 provinces, Canada Pahwa et al. (2012)44
MMi Case-control 342 cases + 1,357 controls 6 provinces, Canada Kachuri et al. (2013)43
MMi Case-control 547 cases + 2,700 controls USA, Canada Presutti et al. (2016)45
NHLj Case-control 858 cases + 1,821 controls Germany Richardson et al. (2008)35
NHLj Cohort 56,222 IA and NC, USA Park et al. (2009)42
NHLj Case-control 649 cases + 1,298 controls Shanghai, China Wong et al. (2010)31
NHLj Case-control 513 cases + 1,506 controls 6 provinces, Canada Hohenadel et al. (2011)40
NHLj Case-control 75 cases + 321 controls Saskatchewan, Canada Karunanayake et al. (2013)39
NHLj Cohort 54,306 IA and NC, USA Alavanja et al. (2014)41
NHLj Case-control 1,317 cases + 2,634 controls Brazil Boccolini et al. (2016)36
Pancreatic Case-control 93 cases + 82,503 controls IA and NC, USA Andreotti et al. (2009)54
Prostate Cohort 47,822 IA and NC, USA Christensen et al. (2010)52
Prostate Case-control 1,153 cases + 3,999 controls Canada Band et al. (2011)50
Prostate Case-control 173 cases + 162 controls CA, USA Cockburn et al. (2011)49
Prostate Cross-sectional 2,938 Saskatchewan, Canada Sharma et al. (2016)51
Several typesa Cohort 19,717 IA and NC, USA Bonner et al. (2007)14
Several types Ecologic 25,110,289 USA Carozza et al. (2008)17
Several typesa Cohort 49,762 IA and NC, USA Koutros et al. (2008)15
Several typesa Cohort 47,625 IA and NC, USA Mozzachio et al. (2008)12
Several typesa Cohort 48,986 IA and NC, USA Greenburg et al. (2008)13
Several types Cohort 48,378 IA and NC, USA Van Bemmel et al. (2008)9
Several types Case-control 1,778 cases + 1,802 controls TX, USA Carozza et al. (2009)18
Several types Cohort 19,655 IA and NC, USA Lynch et al. (2009)10
Several types Cohort 44,624 IA and NC, USA Bonner et al. (2010)11
Several types Cohort 62,960 Great Britain Frost el al. (2011)48
Several types Case-control 34,205 cases + 1,832,969 controls Andalusia, Spain Parrón et al. (2014)34
Several types Cohort 30,003 IA and NC, USA Lerro et al. (2015)71
Several types Case-control 887 cases + 11,491 controls Italy Salerno et al. (2016)19
Several types Case-control 3,350 cases + 20,365 controls Spain Gómez-Barroso et al. (2016)16
Several types Cohort 70,570 Canada Kachuri et al. (2017)37
Several types Cohort 181,842 France Lemarchand et al. (2017)20
Stomach Cohort 53,588 IA and NC, USA Barry et al. (2012)55
STSk Case-control 357 cases + 1,506 controls 6 provinces, Canada Pahwa et al. (2011)80
Thyroid Cohort 36,357 IA and NC, USA Freeman et al., (2011)82
Uveal melanomaa Case-control 293 cases + 3,198 controls 9 European countries1 Behrens et al. (2012)79

aNot significantly associated with pesticides;

bcentral nervous system;

chepatocellular carcinoma;

dHodgkin lymphoma;

eacute lymphoblastic leukemia;

facute myeloid leukemia;

glymphohematopoietic cancer;

hmyelodysplastic syndromes;

imultiple myeloma;

jnon-Hodgkin lymphoma;

ksoft tissue sarcoma;

lDenmark, Latvia, France, Germany, Italy, Sweden, Spain, Portugal, and UK.

Chart 2 Pesticides positively associated with cancer among studies that presented Odd Ratios, Relative Risks, or Hazard Ratios 

Cancer type associated Pesticide Pesticide chemical groupe Pesticide according to the pest it controls RR, OR, or HR with 95% confidence intervalg p-value for linear trend Comparison groupsh References
All types EPTC Thiocarbamate Herbicide RR=1.28 (1.09-1.50) <0.01 Highly exposed (≥ 50 LD) vs non-exposed Van Bemmel et al. (2008)
All types Butylate Thiocarbamate Herbicide RR=1.70 (1.20-2.40) 0.01 Highly exposed (≥ 57 LD) vs low exposed (1-9 LD) Lynch et al. (2009)
All types Terbufos Organophosphate Insecticide HR=1.21 (1.06-1.37) >0.05 Highly exposed (>352 IWLD) vs non-exposed Bonner et al. (2010)
Bladder Imazethapyr Imidazolinone Herbicide RR=2.37 (1.20-4.68) 0.01 T3, upper half (≥311.9 IWLD) vs non-exposed Koutros et al. (2009)
Bladder Imazaquin Imidazolinone Herbicide RR=1.54 (1.05-2.26) <0.05 Ever vs never use Koutros et al. (2016)
Bladder Bentazon Thiadiazinol Herbicide RR=1.55 (1.10-2.19) <0.05 Ever vs never use Koutros et al. (2016)
Bladder Bromoxynil Nitrile Herbicide RR=1.51 (1.04-2.20) <0.05 Ever vs never use Koutros et al. (2016)
Bladder Chloramben Benzoic acid Herbicide RR=1.56 (1.10-2.22) <0.05 Ever vs never use Koutros et al. (2016)
Bladder Diclofop-methyl Chlorinated phenol Herbicide RR=1.85 (1.01-3.42) <0.05 Ever vs never use Koutros et al. (2016)
Bladder DDT Organochlorine Insecticide RR=1.40 (1.10-1.80) <0.05 Ever vs never use Koutros et al. (2016)
Bladder Imazethapyr Imidazolinone Herbicide RR=3.03 (1.46-6.29) 0.004 Q4 vs non-exposed, among never smokers Koutros et al. (2016)
Bladder 2,4,5-T Chlorinated phenol Herbicide RR=2.64 (1.23-5.68) 0.02 T3 vs non-exposed, among never smokers Koutros et al. (2016)
Bladder 2,4-D Chlorinated phenol Herbicide RR=1.88 (0.94-3.77) 0.02 Q4 vs non-exposed, among never smokers Koutros et al. (2016)
Bladder Glyphosate Herbicide RR=1.93 (0.95-3.91) 0.03 Q4 vs non-exposed, among never smokers Koutros et al. (2016)
Breast Organophosphate Insecticide RR=1.20 (1.01-1.43) Ever vs never use Lerro et al. (2015)
Colon Trifluralin Dinitroaniline Herbicide RR=1.76 (1.05-2.95) 0.036 T3 (upper half) vs non-exposed Kang et al. (2008)
Colon EPTC Thiocarbamate Herbicide RR=2.09 (1.26-3.47) <0.01 Highly exposed (≥ 50 LD) vs non-exposed Van Bemmel et al. (2008)
Colon Imazethapyr Imidazolinone Herbicide RR=1.78 (1.08-2.93) 0.02 T3 (upper half) vs non-exposed Koutros et al. (2009)
Colon Carbofuran Carbamate Insecticide HR=1.10 (1.04-1.17) Ever vs never use among males Andreotti et al. (2010)
Colon Metolachlor Chloroacetanilide Herbicide HR=1.09 (1.04-1.15) Ever vs never use among males Andreotti et al. (2010)
Colon Alachlor Chloroacetanilide Herbicide HR=1.08 (1.03-1.13) Ever vs never use among males Andreotti et al. (2010)
Cutaneous Melanoma Carbaryl Carbamate Insecticide OR=1.7 (1.1-2.5) 0.013 Highly exposed (≥ 56 LD) vs non-exposed Dennis et al. (2010)
Cutaneous Melanoma Parathion Organophosphate Insecticide OR=2.4 (1.3-4.4) 0.003 Highly exposed (≥ 56 LD) vs non-exposed Dennis et al. (2010)
Cutaneous Melanoma Maneb/ mancozeb Dithiocarbamate Fungicide OR=2.4 (1.2-4.9) 0.006 Highly exposed (≥ 63 LD) vs non-exposed Dennis et al. (2010)
Follicular cell lymphoma Metolachlor Chloroacetanilide Herbicide RR=2.89 (1.13-7.38) 0.03 Q4 (>108.5 LD) vs non-exposed Silver et al. (2015)
Hodgkin lymphoma Chlorpyrifos Organophosphate Insecticide OR=5.26 (1.56-17.79) Exposed vs non-exposed Karunanayake et al. (2012)
Hodgkin lymphoma Dichlorprop Chlorophenoxy Herbicide OR=6.35 (1.56-25.92) Exposed vs non-exposed Pahwa et al. (2009)
Hepatocellular carcinoma Organochlorine Insecticide OR=1.87 (1.17-2.99) Q4 (>14.53 kg km-2) vs others Vopham et al. (2015)
Leukemia EPTC Thiocarbamate Herbicide RR=2.36 (1.16-4.84) 0.02 Highly exposed (≥ 50 LD) vs non-exposed van Bemmel et al. (2008)
Leukemia Terbufos Organophosphate Insecticide HR=2.38 (1.35-4.21) >0.05 Moderately exposed (107<IWLD>352) vs non-exposed Bonner et al. (2010)
Leukemia (ALLa) Organophosphate Insecticide OR=1.6 (1.0-2.7) Moderately exposed (1-79 lb/mi2) vs low exposure (<1 lb/mi2) Rull et al. (2009)
Leukemia (ALLa) Chlorinated phenol OR=2.0 (1.0-3.8) Moderately exposed (1-7 lb/mi2) vs low exposure (<1 lb/mi2) Rull et al. (2009)
Leukemia (ALLa) Triazine Herbicide OR=1.9 (1.0-3.7) Moderately exposed (1-27 lb/mi2) vs low exposure (<1 lb/mi2) Rull et al. (2009)
Leukemia (ALLa) Fumigant OR=1.7 (1.0-3.1) Moderately exposed (1-549 lb/mi2) vs low exposure (<1 lb/mi2) Rull et al. (2009)
Leukemia (ALLa) Permethrin Pyrethroid Insecticide OR=2.47 (1.17-5.25) Children up to 11 months Ferreira et al. (2013)
Leukemia (ALLa) Imiprothrin Pyrethroid Insecticide OR=2.61 (1.06-6.93) Children up to 11 months Ferreira et al. (2013)
Leukemia (ALLa) Esbiothrin Pyrethroid Insecticide OR=3.03 (1.13-8.09) Children up to 11 months Ferreira et al. (2013)
Leukemia (AMLb) Prallethrin Pyrethroid Insecticide OR=8.06 (1.17-55.65) Children up to 11 months Ferreira et al. (2013)
Leukemia (AMLb) Permethrin Pyrethroid Insecticide OR=7.28 (2.60-20.38) Children up to 11 months Ferreira et al. (2013)
Leukemia (AMLb) Tetramethrin Pyrethroid Insecticide OR=6.19 (2.07-18.56) Children up to 11 months Ferreira et al. (2013)
Leukemia (AMLb) d-Allethrin Pyrethroid Insecticide OR=6.19 (2.07-18.56) Children up to 11 months Ferreira et al. (2013)
Leukemia (AMLb) Esbiothrin Pyrethroid Insecticide OR=3.71 (1.18-11.62) Children between 12 and 23 months Ferreira et al. (2013)
Leukemia (AMLb) d-phenothrin Pyrethroid Insecticide OR=8.43 (1.59-44.75) Children between 12 and 23 months Ferreira et al. (2013)
LHCc Butylate Thiocarbamate Herbicide RR=1.84 (1.14-2.97) 0.01 Highly exposed (≥26 LD) vs non-exposed Lynch et al. (2009)
LHCc Metribuzin Triazole Herbicide RR=2.07 (0.99-4.29) 0.02 Highly exposed (≥174.4 IWLD) vs low exposed Delancey et al. (2009)
LHCc Terbufos Organophosphate Insecticide HR=1.85 (1.31-2.62) >0.05 Moderately exposed (107<IWLD>352) vs non-exposed Bonner et al. (2010)
Liver Metolachlor Chloroacetanilide Herbicide RR=3.99 (1.43-11.1) <0.01 Q4 (>108.5 LD) vs non-exposed Silver et al. (2015)
Lungs Diazinon Organophosphate Insecticide RR=1.60 (1.11-2.31) 0.02 Highly exposed (>38.8 LD) vs non-exposed Jones et al. (2015)
Lungs Chlorimuron ethyl Sulfenylurea Herbicide HR=1.74 (1.02-2.96) 0.18 Fourth quartile vs non-exposed, based on LD Bonner et al. (2017)
Melanoma Carbaryl Carbamate Insecticide RR=3.55 (1.27-9.96) 0.07 Moderately exposed (57-175 LD) vs non-exposed Mahajan et al. (2007)
Melanoma Carbaryl Carbamate Insecticide RR=4.11 (1.33-12.75) 0.07 Highly exposed (>175 LD) vs non-exposed Mahajan et al. (2007)
Myelodysplastic syndromes Paraquat Organic Herbicide OR=4.90 (1.05-22.75) Exposed vs non-exposed Avgerinou et al. (2017)
Multiple Myeloma Captan Phentolamine Fungicide OR=2.35 (1.03-5.35) Exposed vs non-exposed Pahwa et al. (2012)
Multiple Myeloma Carbamate Insecticide OR=1.90 (1.11-3.27) Exposed vs non-exposed Pahwa et al. (2012)
Multiple Myeloma Mecoprop Phenoxy Herbicide OR=1.89 (1.15-3.12) Exposed vs non-exposed Pahwa et al. (2012)
Multiple Myeloma Mecoprop Phenoxy Herbicide OR=1.94 (1.19-3.19) Exposed vs non-exposed Kachuri et al. (2013)
Multiple Myeloma Carbaryl Carbamate Insecticide OR=2.71 (1.47-5.00) Exposed vs non-exposed Kachuri et al. (2013)
Multiple Myeloma Lindane Organochlorine Insecticide OR=2.37 (1.08-5.16) Exposed vs non-exposed Kachuri et al. (2013)
Multiple Myeloma Captan Phentolamine Fungicide OR=2.96 (1.40-6.24) Exposed vs non-exposed Kachuri et al. (2013)
Multiple Myeloma Carbaryl Carbamate Insecticide OR=2.02 (1.28-3.21) Ever vs never use Presutti et al. (2016)
Multiple Myeloma Captan Phentolamine Fungicide OR=1.98 (1.04-3.77) Ever vs never use Presutti et al. (2016)
Multiple Myeloma DDT Organochlorine Insecticide OR=1.44 (1.05-1.97) Ever vs never use Presutti et al. (2016)
Multiple Myeloma Permethrin Pyrethroid Insecticide RR=3.1 (1.5-6.2) 0.002 Highly exposed (>50.75 LD) vs non-exposed Alavanja et al. (2014)
Multiple Myeloma Permethrin Pyrethroid Insecticide RR=5.72 (2.76-11.87) <0.01 Highly exposed (> 50.75 LD) vs non-exposed Rusiecki et al. (2009)
NHLd Paraquat Organic Herbicide RR=1.51 (1.01-2.26) Ever vs never used Park et al. (2009)
NHLd Butylate Thiocarbamate Herbicide RR=2.94 (1.49-5.76) 0.002 Highly exposed (≥ 26 LD) vs non-exposed Lynch et al. (2009)
NHLd Terbufos Organophosphate Insecticide HR=1.94 (1.16-3.22) >0.05 Moderately exposed (107<IWLD>352) vs non-exposed Bonner et al. (2010)
NHLd All pesticides OR=1.63 (1.20-2.21) 0.01 Highly exposed (≥5 pesticides) vs non-exposed Hohenadel et al. (2011)
NHLd Herbicide OR=1.62 (1.18-2.22) 0.02 Moderately exposed (2-4 pesticides) vs non-exposed Hohenadel et al. (2011)
NHLd Insecticide OR=1.67 (1.25-2.24) <0.01 Moderately exposed (2-4 pesticides) vs non-exposed Hohenadel et al. (2011)
NHLd Fungicide OR=1.72 (1.07-2.77) 0.04 Highly exposed (≥2 pesticides) vs non-exposed Hohenadel et al. (2011)
NHLd Phenoxy Herbicide OR=1.78 (1.27-2.50) 0.01 Highly exposed (≥2 pesticides) vs non-exposed Hohenadel et al. (2011)
NHLd Organophosphate Insecticide OR=1.69 (1.04-2.74) <0.01 Highly exposed (≥2 pesticides) vs non-exposed Hohenadel et al. (2011)
NHLd Potentially carcinogenic OR=1.94 (1.17-3.23) 0.01 Highly exposed (≥5 pesticides) vs non-exposed Hohenadel et al. (2011)
NHLd DDT Organochlorine Insecticide RR=1.7 (1.1-2.6) 0.02 Highly exposed (≥56 LD) vs non-exposed Alavanja et al. (2014)
NHLd Lindane Organochlorine Insecticide RR=2.5 (1.4-4.4) 0.004 Highly exposed (≥56 LD) vs non-exposed Alavanja et al. (2014)
NHLd Terbufos Organophosphate Insecticide RR = 1.2 (1.0-1.5) Ever vs never exposure Alavanja et al. (2014)
Ovary Diazinon Organophosphate Insecticide RR=1.87 (1.02-3.43) Ever vs never use Lerro et al. (2015)
Pancreatic EPTC Thiocarbamate Herbicide OR=1.8 (1.0-3.3) Ever vs never exposure Andreotti et al. (2009)
Pancreatic EPTC Thiocarbamate Herbicide OR=2.5 (1.1-5.4) 0.01 Highly exposed (≥ 118 IWLD) vs non-exposed Andreotti et al. (2009)
Pancreatic Pendimethalin Dinitroanilines Herbicide OR=3.0 (1.3-7.2) 0.01 Highly exposed (≥ 117 IWLD) vs non-exposed Andreotti et al. (2009)
Prostate Butylate Thiocarbamate Herbicide RR=1.44 (1.04-2.00) 0.03 Highly exposed (≥ 57 LD) vs non-exposed Lynch et al. (2009)
Prostate Coumaphos Organophosphate Insecticide RR=1.91 (1.23-2.95) 0.004 Ever vs never use Christensen et al. (2010)
Prostate Methyl bromide Organobromine Fungicide OR=1.62 (1.02-2.59) Exposed vs non-exposed Cockburn et al. (2011)
Prostate Organochlorinef Insecticide OR=1.64 (1.02-2.63) Exposed vs non-exposed Cockburn et al. (2011)
Prostate DDT Organochlorine Insecticide OR=1.68 (1.04-2.70) 0.03 Highly exposed vs non-exposed Band et al. (2011)
Prostate Lindane Organochlorine Insecticide OR=2.02 (1.15-3.55) 0.03 Highly exposed vs non-exposed Band et al. (2011)
Prostate 3,5-dinitro-o-cresol Organic Insecticide OR=1.80 (1.05-3.08) 0.03 Highly exposed vs non-exposed Band et al. (2011)
Prostate Azinphos-methyl Organophosphate Insecticide OR=1.88 (1.06-3.32) 0.01 Highly exposed vs non-exposed Band et al. (2011)
Prostate Carbaryl Carbamate Insecticide OR=1.73 (1.09-2.74) 0.01 Highly exposed vs non-exposed Band et al. (2011)
Prostate Diazinon Organophosphate Insecticide OR=1.93 (1.21-3.08) 0.02 Highly exposed vs non-exposed Band et al. (2011)
Prostate Malathion Organophosphate Insecticide OR=1.49 (1.02-2.18) 0.03 Highly exposed vs non-exposed Band et al. (2011)
Prostate 2,4-DB Chlorinated phenol Herbicide OR=2.19 (1.06-4.50) 0.02 Highly exposed vs non-exposed Band et al. (2011)
Prostate MCPA Chlorinated phenol Herbicide OR=2.31 (1.09-4.88) 0.02 Highly exposed vs non-exposed Band et al. (2011)
Prostate Simazine Triazine Herbicide OR=1.89 (1.08-3.33) 0.01 Highly exposed vs non-exposed Band et al. (2011)
Prostate Copper sulfate Inorganic Fungicide OR=1.74 (1.04-2.91) 0.05 Highly exposed vs non-exposed Band et al. (2011)
Prostate Dichlone Napthoquinone Fungicide OR=1.88 (1.01-3.52) 0.02 Highly exposed vs non-exposed Band et al. (2011)
Prostate Ferbam Carbamate Fungicide OR=1.90 (1.09-3.30) 0.02 Highly exposed vs non-exposed Band et al. (2011)
Prostate Maneb Dithiocarbamate Fungicide OR=1.90 (1.09-3.30) 0.02 Highly exposed vs non-exposed Band et al. (2011)
Prostate Sulfur Fungicide OR=1.81 (1.12-2.92) 0.02 Highly exposed vs non-exposed Band et al. (2011)
Prostate Ziram Carbamate Fungicide OR=1.83 (1.08-3.10) 0.03 Highly exposed vs non-exposed Band et al. (2011)
Prostate Captan Phentolamine Fungicide OR=1.76 (1.12-2.78) 0.02 Low exposed vs non-exposed Band et al. (2011)
Prostate Terbufos Organophosphate Insecticide HR=1.28 (1.06-1.55) >0.05 Moderately exposed (107<IWLD>352) vs non-exposed Bonner et al. (2010)
Prostate Insecticide + fungicide OR=2.23 (1.15-4.33) Men exposed vs non-exposed Sharma et al. (2016)
Stomach Methyl bromide Organobromine Fungicide RR=3.13 (1.25-7.80) 0.02 Highly exposed (>765 IWLD) vs non-exposed Barry et al. (2012)
Soft tissue sarcoma Aldrin Organochlorine Insecticide OR=3.71 (1.00-13.76) Exposed vs non-exposed Pahwa et al. (2011)
Soft tissue sarcoma Diazinon Organophosphate Insecticide OR=3.31(1.78-6.23) Exposed vs non-exposed Pahwa et al. (2011)
Thyroid Atrazine Organic Herbicide RR=4.84 (1.31-17.93) 0.08 Q4 (>178.5 IWLD) vs Q1(≤20 IWLD) Freeman et al. (2011)
Thyroid Malathion Organophosphate Insecticide RR=2.04 (1.14-3.63) Ever vs never use Lerro et al. (2015)

aAcute lymphoblastic leukemia.

bAcute myeloid leukemia.

cLymphohematopoietic cancer.

dNon-Hodgkin lymphoma.

eAccording to the Pesticide Management Education Program (http://pmep.cce.cornell.edu/profiles/index.html).

fDicofol, dieldrin, dienochlor, endosulfan, heptachlor, lindane, methoxychlor, and toxaphene.

gOR= Odd Ratio; RR=Relative Risk; HR= Hazard Ratio.

hLD=lifetime days of pesticide use, i.e., the product of years of use of a specific pesticide and the number of days used per year; IWLD= intensity-weighted lifetime days of use, i.e., the product of lifetime days of use and a measure of exposure intensity; T3= third tertile, Q4=fourth quantile.

Chart 3 Registration status of pesticides positively associated with cancer - European Union, United States, and Brazil 

Pesticide Registration Status
European Uniona United Statesb Brazilc
2,4,5-T Not Approved Banned or Severely Restricted Banned
2,4-D Approved Banned or Severely Restricted Approved, but under review
2,4-DB Approved Registration Review Banned
3,5-dinitro-o-cresol Not registered Not registered Not registered
Aldrin Not Approved Banned or Severely Restricted Banned
Alachlor Not Approved Reregistration Approved
Atrazine Not Approved Registration Review Approved
Azinphos-methyl Not Approved Banned or Severely Restricted Not approved
Bentazon Approved Registration Review Approved
Bromoxynil Approved Registration Review Approved
Butylate Not Approved Registration Review Banned
Captan Approved Registration Review Approved
Carbaryl Not Approved Registration Review Approved
Carbofuran Not Approved Banned or Severely Restricted Banned
Chloramben Not Approved Approved Banned
Chlorimuron ethyl Not Approved Registration Review Approved
Chlorpyrifos Approved Registration Review Approved
Copper sulfate Approved Registration Review Approved
Coumaphos Not Approved Registration Review Not registered
d-Allethrin Not Approved Registration Review Approved
DDT Not Approved Banned or Severely Restricted Banned
Diazinon Not Approved Registration Review Approved
Dichlone Not Approved Approved Not registered
Dichlorprop Not Approved Approved Approved
Diclofop-methyl Approved Registration Review Approved
d-phenothrin Not Approved Registration Review Approved
EPTC Not Approved Registration Review Banned
Esbiothrin Not registered Registration Review Approved
Ferbam Not Approved Reregistration Not registered
Glyphosate Approved Registration Review Approved, but under review
Imazaquin Approved Registration Review Approved
Imazethapyr Not Approved Registration Review Approved
Imiprothrin Not registered Registration Review Approved
Lindane Not Approved Banned or Severely Restricted Banned
Malathion Approved Registration Review Approved
Maneb Not Approved Registration Review Banned
Mancozeb Approved Reregistration Approved
MCPA Approved Registration Review Approved
Mecoprop (MCPP) Not Approved Reregistration Not registered
Methyl bromide Not Approved Registration Review Approved
Metolachlor Not Approved Registration Review Approved
Metribuzin Approved Registration Review Approved
Paraquat Not Approved Approved Restricted, but banned
starting in 2020
Parathion Not Approved Banned or Severely Restricted Banned
Pendimethalin Approved Registration Review Approved
Permethrin Not Approved Registration Review Approved
Prallethrin Not registered Registration Review Approved
Simazine Not Approved Registration Review Approved
Sulfur Approved Registration Review Approved
Terbufos Not Approved Registration Review Approved
Tetramethrin Not Approved Registration Review Approved
Trifluralin Not Approved Registration Review Approved
Ziram Approved Reregistration Banned

aEuropean Comission. EU Pesticides database [internet]. [accessed 2018 Aug 29]. Available at: http://ec.europa.eu/food/plant/pesticides/eu-pesticides-database/public/?event=activesubstance.selection&language=EN.

bUSEPA. [internet]. [accessed 2018 Aug 29]. Available at: https://iaspub.epa.gov/apex/pesticides/f?p=CHEMICALSEARCH:1: and http://scorecard.goodguide.com/chemical-groups/one-list.tcl?short_list_name=brpest.

cANVISA. [internet]. [accessed 2018 Aug 29]. Available at: http://portal.anvisa.gov.br/registros-e-autorizacoes/agrotoxicos/produtos/monografia-de-agrotoxicos.

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 EPTC9 and butylate10 lifetime exposure days (LD) were associated to all cancers. Additionally, moderate and high exposures to terbufos also increased overall cancer hazard ratio11. On the other hand, some cohort studies investigated specific pesticides such as chlorothalonil12, captan13, malathion14, and dichlorvos15, although not finding any association with cancer.

To reside near crops was reported to increase cancer risk in children younger than 1416 or 15 years old17. However, another study18 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 range19. Lemarchand et al.20 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 farm21 or near crops16 exposed to pesticides22-24, butylate herbicide10, metribuzin herbicide22, or terbufos insecticide11.

Leukemia primarily affects children. Several studies found association between different types of childhood leukemia and pesticide exposure25-27. Residing near certain crops28, or in counties of high level of agricultural activity17, was also found to significantly increase the risk of childhood cancer. Although Malagoli et al.29 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 leukemia30. In adults, increased leukemia risk was significantly associated with exposure to EPTC herbicide9 and terbufos insecticide11. 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 fertilizers31.

Hodgkin Lymphoma (HL) in males of 19 years of age or older was significantly associated with exposure to the organophosphate insecticide chlorpyrifos32 and the herbicide dichlorprop33. Hodgkin’s disease and Non-Hodgkin Lymphoma (NHL) were significantly reduced in districts with low pesticides exposure compared to those with high exposure34.

Non-Hodgkin lymphoma risk factors include: being an agricultural worker35-37 or a farmer35,38,39; living in a farm or in communities between 1,000 and 10,000 people39; being exposed to pesticides39, potentially carcinogenic pesticides40, herbicides35,38,40, insecticides38,40, or fungicides(40.) Some specific insecticides such as DDT41, lindane41, and terbufos11,41, as well as some specific herbicides such as butylate10 and paraquat42, 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 studies43-45 showed that these pesticides increased MM risk, one cohort study41 could not find significant associations. Different results also appeared for DDT and lindane insecticides. Presutti et al.45 found DDT to be linked to MM, but could not trace significant correlation between lindane and MM. Conversely, Kachuri et al.43 and Pahwa et al.44 found DDT not to be linked to MM, while lindane showed a significant association. Two cohort studies investigated permethrin insecticide41,46, and other two case-control studies43,44 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 MM41,43-45. 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 3 organochlorines43. 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)47. Female crop farmers37, as well as female and male pesticide users48, suffered higher incidences of MM. Similarly, a study20 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 butylate10, methyl bromide49, a group of organochlorine insecticide49, and terbufos11 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 males50,51. Prostate cancer risk was higher among male agricultural workers20,37 and men exposed to coumaphos who reported a family history of that cancer52.

Primary testicular tumors are the most common solid malignant tumor in men aged 20 to 34 years in the United States53 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)48.

Among malignant neoplasms of digestive organs, the herbicides EPTC and pendimethalin were associated with pancreatic cancer among pesticide applicators and their spouses37,54. Stomach cancer risk significantly increased with exposure to methyl bromide55 and in districts with greater pesticide use34. Colorectal cancer risk was significantly higher among farmers (OR=1.529, 95% CI: 1.011-2.314)19, 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)56. A higher prevalence of colon cancer was also observed among male pesticide applicators exposed to EPTC9, trifluralin57, carbofuran, metolachlor, and alachlor58. 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 use59. 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 activity17,34,60-62. In contrast, Jeephet et al.63 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)64, pesticide applicators (HR= 1.96; 95% CI: 1.11-3.47)64, and children living in countries with high level of agricultural activity (OR= 1.3, 95% CI: 1.1-1.4)17. Brain cancer prevalence34 and its mortality65,66 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 pesticides67. Controversially, a study investigating pesticide applicators did not find any positive association between glioma and farm pesticide use68.

As for malignant neoplasms of female genital organs, a study69 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.70 did not find significant associations between breast cancer and fungicide exposure. However, Salerno et al.19 observed that farmers were at significantly higher risk for breast cancer (OR=1.720, 95% CI: 1.039-2.846), and Lerro et al.71 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 use34. Any use of imazethapyr, imazaquin, bentazon, bromoxynil, chloramben, and diclofop-methyl herbicides increased the risk of bladder cancer, as did the insecticide DDT solely72,73. In contrast, a study74 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)17.

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)75. The highest quartile of use of the herbicide chlorimuron ethyl showed high risk of lung cancer76. Significantly higher prevalence was also observed in districts with greater pesticide use34.

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 factors77,78. A higher risk for skin melanoma (SIR= 1.30, 95% CI: 1.00-1.66) was observed among female farm workers20. Additionally, an increased melanoma hazard ratio among male agricultural workers and female crop farmers was also identified37. A study investigated uveal melanoma but could not find positive associations with activities of farming, pesticide application, or pesticide mixing79.

Soft Tissue Sarcoma (STS) was significantly associated to also exposure to aldrin and diazinon among men aged 19 years or older80 as to with high level of agricultural activity (OR=1.7, 95% CI: 1.4-2.0)17. Among British women, it was observed that pesticide users died more often from STS than the national population48. Malignant bone tumors were associated to living in counties with high level of agricultural activity (OR=2.3, 95% CI: 1.8-2.9)17.

Head and neck cancer was reported among men and women residing in rural areas81. Thyroid cancer risk increased with malathion71 and atrazine exposure82. Lip cancer risk was significantly higher among male agricultural workers (HR= 2.14, 95% CI: 1.70-2.70)37 and male farm workers (SIR=2.87, 95% CI: 1.61-4.74)20.

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 fungicides83. 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.

Financial support: non-existent

References

1 World Health Organization. Pesticides [internet]. Genebra: WHO; 2019 [accessed 2017 Sept 10]. Available at: http://www.who.int/topics/pesticides/en/. [ Links ]

2 Garcia EG, Alves Filho JP. Aspectos de prevenção e controle de acidentes no trabalho com agrotóxicos. São Paulo: Fundacentro; 2005. [ Links ]

3 Peres F. Saúde, trabalho e ambiente no meio rural brasileiro. Ciênc. Saúde Colet. 2009; 14:1995-2004. [ Links ]

4 Brito PF, Gomide M, Magalhães V, et al. Familiar agriculture and pesticide exposure?: brief considerations. Cad. Saúde Colet. 2005; 13(4):887-900. [ Links ]

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. [ Links ]

6 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. [ Links ]

7 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. [ Links ]

8 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. [ Links ]

9 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. [ Links ]

10 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. [ Links ]

11 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. [ Links ]

12 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. [ Links ]

13 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. [ Links ]

14 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. [ Links ]

15 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. [ Links ]

16 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. [ Links ]

17 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. [ Links ]

18 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. [ Links ]

19 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. [ Links ]

20 Lemarchand C, Tual S, Levêque-Morlais N, et al. Cancer incidence in the AGRICAN cohort study (2005-2011). Cancer Epidemiol. 2017; 49:175-185. [ Links ]

21 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. [ Links ]

22 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. [ Links ]

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. [ Links ]

24 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. [ Links ]

25 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. [ Links ]

26 Ferreira JD, Couto AC, Pombo-de-Oliveira MS, et al. In utero pesticide exposure and leukemia in Brazilian children &lt;2 years of age. Environ. health perspect. 2013; 121(2):269-275. [ Links ]

27 Kumar A, Vashist M, Rathee R. Maternal factors and risk of childhood leukemia. Asian pac. j. cancer prev. 2014; 15(2):781-784. [ Links ]

28 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. [ Links ]

29 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. [ Links ]

30 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. [ Links ]

31 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. [ Links ]

32 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. [ Links ]

33 Pahwa P, Karunanayake CP, Spinelli JJ, et al. Ethnicity and incidence of Hodgkin lymphoma in Canadian population. BMC cancer. 2009; 9(141):1-9. [ Links ]

34 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. [ Links ]

35 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. [ Links ]

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. [ Links ]

37 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. [ Links ]

38 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. [ Links ]

39 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. [ Links ]

40 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. [ Links ]

41 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. [ Links ]

42 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. [ Links ]

43 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. [ Links ]

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. [ Links ]

45 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. [ Links ]

46 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. [ Links ]

47 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. [ Links ]

48 Frost G, Brown T, Harding AH. Mortality and cancer incidence among British agricultural pesticide users. Occup Med (Lond). 2011; 61(5):303-310. [ Links ]

49 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. [ Links ]

50 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. [ Links ]

51 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. [ Links ]

52 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. [ Links ]

53 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. [ Links ]

54 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. [ Links ]

55 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. [ Links ]

56 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. [ Links ]

57 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. [ Links ]

58 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. [ Links ]

59 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. [ Links ]

60 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. [ Links ]

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. [ Links ]

62 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. [ Links ]

63 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. [ Links ]

64 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. [ Links ]

65 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. [ Links ]

66 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. [ Links ]

67 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. [ Links ]

68 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. [ Links ]

69 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. [ Links ]

70 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. [ Links ]

71 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. [ Links ]

72 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. [ Links ]

73 Koutros S, Silverman DT, Alavanja MCR, et al. Occupational exposure to pesticides and bladder cancer risk. Int J Epidemiol. 2016; 45(3):792-805. [ Links ]

74 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. [ Links ]

75 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. [ Links ]

76 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. [ Links ]

77 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. [ Links ]

78 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. [ Links ]

79 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. [ Links ]

80 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. [ Links ]

81 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. [ Links ]

82 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. [ Links ]

83 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. [ Links ]

Received: March 02, 2019; Accepted: October 04, 2019

Collaborators

Pluth TB (0000-0002-5851-9476)* made substantial contribution to the conception, design, drafting of the work, and to the analysis and interpretation of data. Zanini LAG (0000-0002-3849-6211)* contributed to the critical review of the content, and assisted in data interpretation and drafting of the work. Battisti IDE (0000-0001-9740-4199)* made substantial contribution to the conception and design of the work. All authors approved the final version to be published.

Conflict of interest: non-existent

Creative Commons License This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited