Pesticide Exposure and Bone Tumors: A Systematic Review

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This systematic review evaluates the association between pesticide exposure and the incidence of bone tumors, specifically osteosarcoma and Ewing's sarcoma. Objectives : To systematically review and synthesize the available evidence on the relationship between pesticide exposure and the risk of developing bone tumors. Methods : This systematic review was conducted in the winter of 2024 by searching keywords such as "pesticide exposure," "bone tumors," "osteosarcoma," "Ewing's sarcoma," "agriculture," "cancer risk," and "environmental exposure" in PubMed, Google Scholar databases, ISC, Scopus, and Web of Science without time limits. The search strategy was based on the PRISMA 2020 statement. Results : A total of 20 studies met the inclusion criteria. The findings suggest a significant association between pesticide exposure and an increased risk of both osteosarcoma and Ewing's sarcoma. Conclusions : This review highlights the need for stricter regulations on pesticide use in agriculture and further research to elucidate the mechanisms underlying these associations. Bone Tumor cancer pesticide human health public health osteosarcoma Ewing's sarcoma Figures Figure 1 Introduction Agriculture has long been recognized as a fundamental pillar of human civilization, serving as the primary source of food resources and raw materials essential for societal development and sustenance [1, 2]. From the earliest agrarian societies to modern industrial farming, agriculture has evolved significantly, driven by innovations aimed at increasing productivity and efficiency [3, 4]. However, this progress has not come without challenges, particularly in the realm of public health [5, 6]. One of the most pressing concerns in contemporary agriculture is the widespread use of chemical pesticides, which, while instrumental in enhancing crop yields and managing pest populations, has raised significant public health concerns, especially regarding potential links to cancer [7, 8]. Pesticides are chemical substances specifically designed to prevent, destroy, or repel pests, which encompass a broad range of organisms such as insects, weeds, fungi, and rodents [6, 9]. These chemicals have become indispensable in modern agriculture, enabling farmers to protect crops from devastating losses and maintain high levels of productivity [10, 11]. Despite their utility, the potential adverse effects of pesticides on human health have become a focal point of public health research, particularly concerning their association with cancer risk [12-14]. Among the various cancers linked to pesticide exposure, bone tumors, though relatively rare compared to other malignancies, pose significant health risks due to their aggressive nature and often poor prognosis [7, 15, 16]. Bone tumors, while less common than other types of cancer, are particularly concerning due to their aggressive behavior and the challenges associated with their treatment [17]. Osteosarcoma and Ewing's sarcoma are two of the most prevalent primary bone tumors, particularly among children and adolescents. Osteosarcoma, which typically arises in the long bones such as the femur or tibia, is characterized by the production of immature bone tissue [18, 19]. This malignancy is most commonly diagnosed in teenagers and young adults, with a peak incidence during the adolescent growth spurt, suggesting a potential link to rapid bone growth [20]. Ewing's sarcoma, on the other hand, is a highly aggressive tumor that can occur in either bone or soft tissue. It is most prevalent in young adults and is known for its rapid progression and metastatic potential, often spreading to the lungs or other bones [18, 20, 21]. The rarity of bone tumors, coupled with their aggressive nature, underscores the importance of identifying and understanding potential risk factors, including environmental exposures such as pesticides [22, 23]. Epidemiological studies have increasingly suggested that exposure to certain environmental toxins, including pesticides, may increase the risk of developing these malignancies [24]. Pesticides are known to possess a variety of toxic properties, including genotoxicity, which refers to their ability to induce DNA damage and mutations. Such genetic alterations can lead to carcinogenesis, the process by which normal cells transform into cancer cells [24-26]. Additionally, some pesticides act as endocrine disruptors, interfering with hormonal regulation. This interference can promote tumor growth through mechanisms such as oxidative stress, inflammation, and immune system modulation, all of which are implicated in cancer development [27]. The relationship between pesticide exposure and cancer risk is a topic of considerable interest and debate within the scientific community [28, 29]. A growing body of literature has explored the potential links between pesticide exposure and various cancers, including leukemia, lymphoma, and brain tumors [29, 30]. However, the specific association between agricultural pesticide use and bone tumors remains inadequately explored [31]. This gap in research is partly due to the rarity of bone tumors, which makes it challenging to conduct large-scale epidemiological studies with sufficient statistical power. Moreover, existing studies often face methodological challenges, such as small sample sizes, reliance on self-reported exposure data, and the presence of confounding factors, which can obscure the true relationship between pesticide exposure and bone tumor incidence. For example, study results show a significant association between pesticide exposure and childhood cancers, including osteosarcoma and Ewing's sarcoma [32-35]. Understanding the mechanisms by which pesticides may contribute to cancer development is crucial for elucidating their role in bone tumor incidence. These complex mechanisms underscore the need for comprehensive exposure assessments that account for the mixture of pesticides commonly used in agricultural settings. Given the potential public health implications of pesticide exposure, there is an urgent need for research to elucidate the relationship between agricultural pesticide use and bone tumor incidence. This systematic review aims to critically evaluate existing research on the association between pesticide exposure and the incidence of bone tumors. Methodology This systematic review was conducted in the winter of 2024 by searching keywords such as "pesticide exposure," "bone tumors," "osteosarcoma," "Ewing's sarcoma," "agriculture," "cancer risk," and "environmental exposure" in PubMed, Google Scholar databases, ISC, Scopus, and Web of Science without time limits. Inclusion criteria were considered for writing the article in English, including the original research study, availability of the full text, and alignment with the study objectives. Exclusion criteria: Studies that did not meet a predefined quality threshold based on established criteria (PRISMA 2020 guidelines [36]). Articles with significant methodological flaws or biases that could have compromised the validity of findings. Studies that focused primarily on non-human subjects or in vitro experiments without direct application to human cases. Research that did not address the specified outcomes of interest or failed to provide relevant data. Studies that lacked sufficient detail for extraction of relevant parameters or outcomes. Articles that did not clearly define Pesticide Exposure and Bone Tumors cases or relevant epidemiological metrics. A search strategy based on the PRISMA 2020 statement was used to find relevant studies. A total of 1670 article titles were obtained using the mentioned keywords and search strategy. After removing 320 duplicate titles with EndNote software, 1350 articles remained. Abstracts were then reviewed, resulting in the exclusion of 1040 abstracts. The full text of the remaining 310 articles was examined, leading to the exclusion of 290 articles not related to the study objectives. Finally, 20 articles were selected for inclusion in the study (Diagram 1). Each of the selected studies was reviewed separately by researchers and categorized into approved articles, rejected articles, and articles for re-examination. Researchers exchanged files for review, and joint review of selected articles and approved articles was conducted according to the PRISMA 2020 protocol. The quality of the articles was evaluated using the PRISMA 2020 statement, and they were indexed in valid databases. Results Characteristics of Included Studies The characteristics of included studies are summarized in Table 1: Table 1: The characteristics of the included studies Findings on Pesticide Exposure and Bone Tumors Osteosarcoma The findings indicate that individuals with a history of pesticide use are at a higher risk for developing a specific type of bone cancer known as osteosarcoma. This association clearly indicates that exposure to these chemicals can be considered a significant risk factor for the onset of this particular cancer [37, 38]. The findings indicate that agricultural workers who are exposed to pesticides are at a heightened risk of developing osteosarcoma. This association suggests a significant link between pesticide exposure and the likelihood of developing this particular form of cancer [37-39]. The findings from the study regarding organophosphate exposure indicate a significant association between this type of pesticide and the risk of developing osteosarcoma. Specifically, the results suggest that individuals who have been exposed to organophosphate pesticides are at a heightened risk for this particular bone cancer [40, 41]. Ewing's Sarcoma The findings indicate that household pesticide is associated with an increased risk of developing certain health issues among boys aged 15 years and younger. This connection indicates that exposure to pesticides used in home processes may pose significant health risks for children, particularly young boys [42, 43]. The findings indicate that agricultural workers have an increased risk of developing Ewing's sarcoma compared to non-agricultural workers. This association suggests that certain occupational exposures related to farming may contribute to the development of this specific type of cancer [44, 45]. The findings indicated that children living near agricultural fields treated with pesticides had higher incidences of Ewing's sarcoma [45, 46]. Geographical Variations : The findings indicate that heavy pesticide use in rural areas is associated with an increased risk of bone cancer among males. This association highlights the potential impact of local agricultural practices on cancer incidence rates, particularly in regions where pesticide application is prevalent. The findings suggest that individuals living in rural areas, where pesticides are heavily utilized for agricultural purposes, may be at a greater risk of developing bone cancer [37, 38]. Parental Occupational Exposure : The findings indicate that children whose fathers worked in agriculture have a significantly higher risk of developing Ewing's sarcoma. This suggests that parental occupational exposure, particularly in agricultural settings, may have lasting effects on children's health. The elevated risk for Ewing's sarcoma among children with fathers in agricultural occupations points to potential environmental and chemical exposures associated with farming. Agricultural work often involves the use of various pesticides and herbicides, which may contribute to increased cancer risk in offspring. Additionally, exposure to organic dust and other agricultural materials could also play a role in this association [44, 45, 47]. Specific Pesticides : The results indicate that organophosphates have frequently been identified as potentially carcinogenic agents linked to both osteosarcoma and Ewing's sarcoma. Studies indicate that exposure to these chemicals, commonly used in agricultural practices, may contribute to an increased risk of developing these types of bone cancers. The mechanisms by which organophosphates may induce carcinogenic effects include DNA damage, oxidative stress, and disruption of hormonal functions, all of which can lead to tumorigenesis [46, 48]. The results indicate that organochlorines are also associated with an increased risk for osteosarcoma. A pooled analysis indicated a significant association, pointing to the potential role of these chemicals in the development of this specific type of bone cancer. Organochlorines, like organophosphates, may exert their effects through similar biological mechanisms, including endocrine disruption and genotoxicity [49, 50]. Mechanisms Explored : The findings regarding the carcinogenic potential of pesticides highlight several biological mechanisms through which these chemicals may contribute to cancer development. One significant mechanism is genotoxicity, where certain pesticides cause DNA damage, leading to mutations that can initiate tumor formation. This DNA damage can disrupt normal cellular processes and promote uncontrolled cell growth. Additionally, pesticides can act as endocrine disruptors, interfering with hormonal pathways that regulate cell growth and differentiation. This disruption may lead to abnormal cellular proliferation, further increasing cancer risk. Lastly, pesticides may also modulate immune function, impairing the body’s ability to detect and eliminate cancerous cells, thereby facilitating tumor development [51-53]. Discussion Pesticides, designed to protect crops and control pests, have become ubiquitous in our modern world. While their use has undoubtedly increased agricultural productivity, their potential impact on human health, particularly cancer development, is increasingly recognized. This paper delves into the epidemiological evidence linking pesticide exposure to specific types of cancer, exploring the mechanisms involved and highlighting the need for further research and preventative measures. Pesticide Exposure and Osteosarcoma: A Growing Concern Osteosarcoma, a malignant bone cancer that primarily affects adolescents and young adults, has been associated with a history of pesticide exposure. Research consistently indicates a higher incidence of osteosarcoma among individuals with a history of pesticide use, particularly among agricultural workers exposed to organophosphates and organochlorines. For example, numerous studies have found a significant association between pesticide exposure and the risk of osteosarcoma, especially in males. These findings conclude that exposure to pesticides significantly increases the likelihood of developing osteosarcoma [37-39, 54]. Geographical variations also highlight the impact of pesticide use on cancer incidence. studies revealed a higher incidence of osteosarcoma in rural areas with heavy pesticide application, suggesting a strong correlation between agricultural practices and cancer risk [37, 38]. Ewing's Sarcoma: A Potential Link to Pesticide Exposure Ewing's sarcoma, a rare and aggressive bone cancer, also shows a significant association with pesticide exposure. Children living near agricultural fields treated with pesticides have a higher incidence of Ewing's sarcoma, suggesting a potential link between environmental exposure and the development of this cancer. A study found a statistically significant association between pesticide exposure and Ewing's sarcoma risk, particularly in children [42]. Furthermore, another study also revealed that children whose fathers worked in agriculture have a significantly higher risk of developing Ewing's sarcoma, indicating a potential transgenerational effect of pesticide exposure [43]. Specific Pesticides: A Focus on Organophosphates and Organochlorines Organophosphates and organochlorines are frequently identified as potential carcinogens linked to both osteosarcoma and Ewing's sarcoma. These chemicals, commonly used in agricultural practices, can contribute to an increased risk of developing these cancers through mechanisms such as DNA damage, oxidative stress, and disruption of hormonal functions [16, 55]. Research has consistently shown that exposure to organophosphates can lead to significant health risks. For instance, studies indicate that these pesticides can cause genotoxic effects, resulting in mutations that initiate tumor formation. Additionally, organophosphates have been linked to oxidative stress, which can exacerbate cellular damage and promote cancer development. The endocrine-disrupting properties of these chemicals also play a critical role, as they interfere with hormonal pathways that regulate cell growth and differentiation, potentially leading to abnormal cellular proliferation [56-58]. Moreover, the implications of pesticide exposure extend beyond direct agricultural workers to their families and communities. Children living near agricultural fields treated with these chemicals may face increased risks of developing Ewing's sarcoma due to environmental exposure. This highlights the need for comprehensive public health strategies aimed at reducing pesticide use and promoting safer agricultural practices [49, 50]. Given the growing body of evidence linking pesticide exposure to various cancers, it is imperative that regulatory agencies reassess the safety of these chemicals and implement stricter guidelines to protect vulnerable populations. Public Health Implications Given these findings: There is a pressing need for stricter regulations regarding pesticide use in agriculture due to their potential carcinogenic effects. Public health initiatives should focus on educating agricultural workers about safe handling practices when using pesticides. Monitoring programs should be implemented in high-exposure areas to assess environmental contamination levels regularly. Community awareness campaigns could help inform residents about potential risks associated with living near agricultural areas where pesticides are used extensively. Limitations While this review provides valuable insights into associations between pesticide exposure and bone tumors: Heterogeneity among included studies regarding population characteristics limits generalizability. Many studies relied on self-reported data regarding pesticide use which may introduce recall bias. Confounding factors such as genetic predisposition or lifestyle choices were not always adequately controlled across all analyses. Recommendations for Future Research Future research should focus on longitudinal designs assessing cumulative pesticide exposures over time while controlling for confounding factors such as genetic predisposition or lifestyle choices: Investigate specific types/classes within broader categories like organophosphates or carbamates regarding their individual impacts on tumor development. Conduct biomonitoring assessments alongside epidemiological surveys assessing both environmental levels as well as biological markers indicative of exposure within affected populations. Explore potential interactions between genetic susceptibility markers related specifically toward cancers like osteosarcoma/Ewing’s sarcoma alongside environmental exposures from pesticides utilized during critical developmental windows in childhood/adolescence. Conclusion The findings regarding pesticide exposure and its association with bone tumors, specifically osteosarcoma and Ewing's sarcoma, reveal significant public health concerns. The evidence indicates that individuals with a history of pesticide use, particularly agricultural workers, face an increased risk of developing osteosarcoma. This suggests that exposure to pesticides, especially organophosphates and organochlorines, serves as a critical risk factor for this type of cancer. The mechanisms through which these pesticides may induce carcinogenic effects include DNA damage, oxidative stress, and disruption of hormonal functions, all of which can contribute to tumorigenesis. Moreover, the findings highlight the increased risk of Ewing's sarcoma among children, particularly those whose fathers work in agriculture or who live near treated agricultural fields. This connection underscores the potential long-term health impacts of parental occupational exposure on children. The elevated incidence of Ewing's sarcoma in these populations points to the importance of considering environmental and chemical exposures associated with farming practices. Young boys are particularly vulnerable to these risks, suggesting that household pesticide use may also contribute to adverse health outcomes in pediatric populations. Geographical variations in pesticide use further complicate the issue. The data indicate that heavy pesticide application in rural areas correlates with higher rates of bone cancer among males. This association emphasizes the influence of local agricultural practices on cancer incidence rates and highlights the necessity for targeted public health strategies in regions where pesticide use is prevalent. Understanding these geographical disparities can inform interventions aimed at reducing exposure and mitigating health risks for affected communities. The evidence linking pesticide exposure to an increased risk of osteosarcoma and Ewing's sarcoma necessitates urgent action from public health officials and policymakers. Comprehensive strategies should be developed to educate agricultural workers and their families about the risks associated with pesticide use, promote safer pest management practices, and implement stricter regulations on harmful chemicals. Continued research is essential to further elucidate the mechanisms by which pesticides contribute to cancer development and to ensure protective measures are in place for vulnerable populations. Declarations Ethics approval and consent to participate All procedures performed in the study involving human participants were by the ethical standards of the institutional and national research committee and with the 1975 Helsinki Declaration and its later amendments or comparable ethical standards. Consent for publication Not applicable Availability of data and materials The data that support the findings of this study are available from the corresponding author upon reasonable request. Competing interests The authors declare no conflict of interest, financial or otherwise. Funding Not applicable Authors' contributions "OSA, GS, RM, MK, RR, and HH analyzed and interpreted the data. SD, RR contributor in writing the manuscript. All authors read and approved the final manuscript." 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Thakur J, Rao B, Rajwanshi A, Parwana H, Kumar R: Epidemiological study of high cancer among rural agricultural community of Punjab in Northern India . International journal of environmental research and public health 2008, 5 (5):399-407. Tables Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files table.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6369910","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":452678361,"identity":"53cda9a2-c8df-495b-9f34-37a343f4fe6d","order_by":0,"name":"Omar Saad Ahmed","email":"","orcid":"","institution":"Al-Turath University","correspondingAuthor":false,"prefix":"","firstName":"Omar","middleName":"Saad","lastName":"Ahmed","suffix":""},{"id":452678362,"identity":"0bd1b2cc-371a-43af-aad1-56f747e5bc02","order_by":1,"name":"Gaurav Sanghvi","email":"","orcid":"","institution":"Al-Turath 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Sciences","correspondingAuthor":false,"prefix":"","firstName":"Rasoul","middleName":"","lastName":"Raesi","suffix":""},{"id":452678366,"identity":"712cca51-5f32-4e27-88d9-0ceb9919714c","order_by":5,"name":"Sina Heydari","email":"","orcid":"","institution":"Jiroft University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Sina","middleName":"","lastName":"Heydari","suffix":""},{"id":452678367,"identity":"d117e018-c2b9-4cab-ba77-3960d0b748cb","order_by":6,"name":"Hasan Hosseini","email":"","orcid":"","institution":"Mashhad University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Hasan","middleName":"","lastName":"Hosseini","suffix":""},{"id":452678368,"identity":"59075d1d-6c37-45c9-b799-c17c1e26c2cd","order_by":7,"name":"Salman Daneshi","email":"data:image/png;base64,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","orcid":"","institution":"Jiroft University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Salman","middleName":"","lastName":"Daneshi","suffix":""}],"badges":[],"createdAt":"2025-04-03 13:53:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6369910/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6369910/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82297255,"identity":"5b40ce85-5ba2-4e91-acba-fd41eb3a7000","added_by":"auto","created_at":"2025-05-08 20:03:54","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":395093,"visible":true,"origin":"","legend":"\u003cp\u003eDiagram 1: The process of searching and screening selected articles based on PRISMA 2020 guidelines\u003c/p\u003e","description":"","filename":"figure.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6369910/v1/03029620df00b222a285b0b0.jpg"},{"id":84316269,"identity":"e2dbccf0-42ef-4e8f-995e-5c701d633331","added_by":"auto","created_at":"2025-06-10 13:32:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2999326,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6369910/v1/3b7035b0-b135-4cb4-b64a-4b58f8fcf3ba.pdf"},{"id":82297253,"identity":"70526250-27c8-46e6-9706-6cdc7824c7ad","added_by":"auto","created_at":"2025-05-08 20:03:54","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":13211,"visible":true,"origin":"","legend":"","description":"","filename":"table.docx","url":"https://assets-eu.researchsquare.com/files/rs-6369910/v1/5e32a3b84e7d6d4cadccc70c.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pesticide Exposure and Bone Tumors: A Systematic Review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAgriculture has long been recognized as a fundamental pillar of human civilization, serving as the primary source of food resources and raw materials essential for societal development and sustenance [1, 2]. From the earliest agrarian societies to modern industrial farming, agriculture has evolved significantly, driven by innovations aimed at increasing productivity and efficiency [3, 4]. However, this progress has not come without challenges, particularly in the realm of public health [5, 6]. One of the most pressing concerns in contemporary agriculture is the widespread use of chemical pesticides, which, while instrumental in enhancing crop yields and managing pest populations, has raised significant public health concerns, especially regarding potential links to cancer [7, 8].\u003c/p\u003e\n\u003cp\u003ePesticides are chemical substances specifically designed to prevent, destroy, or repel pests, which encompass a broad range of organisms such as insects, weeds, fungi, and rodents [6, 9]. These chemicals have become indispensable in modern agriculture, enabling farmers to protect crops from devastating losses and maintain high levels of productivity [10, 11]. Despite their utility, the potential adverse effects of pesticides on human health have become a focal point of public health research, particularly concerning their association with cancer risk [12-14]. Among the various cancers linked to pesticide exposure, bone tumors, though relatively rare compared to other malignancies, pose significant health risks due to their aggressive nature and often poor prognosis [7, 15, 16]. Bone tumors, while less common than other types of cancer, are particularly concerning due to their aggressive behavior and the challenges associated with their treatment [17]. Osteosarcoma and Ewing's sarcoma are two of the most prevalent primary bone tumors, particularly among children and adolescents. Osteosarcoma, which typically arises in the long bones such as the femur or tibia, is characterized by the production of immature bone tissue [18, 19]. This malignancy is most commonly diagnosed in teenagers and young adults, with a peak incidence during the adolescent growth spurt, suggesting a potential link to rapid bone growth [20]. Ewing's sarcoma, on the other hand, is a highly aggressive tumor that can occur in either bone or soft tissue. It is most prevalent in young adults and is known for its rapid progression and metastatic potential, often spreading to the lungs or other bones [18, 20, 21].\u003c/p\u003e\n\u003cp\u003eThe rarity of bone tumors, coupled with their aggressive nature, underscores the importance of identifying and understanding potential risk factors, including environmental exposures such as pesticides [22, 23]. Epidemiological studies have increasingly suggested that exposure to certain environmental toxins, including pesticides, may increase the risk of developing these malignancies [24]. Pesticides are known to possess a variety of toxic properties, including genotoxicity, which refers to their ability to induce DNA damage and mutations. Such genetic alterations can lead to carcinogenesis, the process by which normal cells transform into cancer cells [24-26]. Additionally, some pesticides act as endocrine disruptors, interfering with hormonal regulation. This interference can promote tumor growth through mechanisms such as oxidative stress, inflammation, and immune system modulation, all of which are implicated in cancer development [27].\u003c/p\u003e\n\u003cp\u003eThe relationship between pesticide exposure and cancer risk is a topic of considerable interest and debate within the scientific community [28, 29]. A growing body of literature has explored the potential links between pesticide exposure and various cancers, including leukemia, lymphoma, and brain tumors [29, 30]. However, the specific association between agricultural pesticide use and bone tumors remains inadequately explored [31]. This gap in research is partly due to the rarity of bone tumors, which makes it challenging to conduct large-scale epidemiological studies with sufficient statistical power. Moreover, existing studies often face methodological challenges, such as small sample sizes, reliance on self-reported exposure data, and the presence of confounding factors, which can obscure the true relationship between pesticide exposure and bone tumor incidence. For example, study results show a significant association between pesticide exposure and childhood cancers, including osteosarcoma and Ewing's sarcoma [32-35]. Understanding the mechanisms by which pesticides may contribute to cancer development is crucial for elucidating their role in bone tumor incidence. These complex mechanisms underscore the need for comprehensive exposure assessments that account for the mixture of pesticides commonly used in agricultural settings. Given the potential public health implications of pesticide exposure, there is an urgent need for research to elucidate the relationship between agricultural pesticide use and bone tumor incidence. This systematic review aims to critically evaluate existing research on the association between pesticide exposure and the incidence of bone tumors.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cp\u003eThis systematic review was conducted in the winter of 2024 by searching keywords such as \"pesticide exposure,\" \"bone tumors,\" \"osteosarcoma,\" \"Ewing's sarcoma,\" \"agriculture,\" \"cancer risk,\" and \"environmental exposure\" in PubMed, Google Scholar databases, ISC, Scopus, and Web of Science without time limits. Inclusion criteria were considered for writing the article in English, including the original research study, availability of the full text, and alignment with the study objectives. Exclusion criteria: Studies that did not meet a predefined quality threshold based on established criteria (PRISMA 2020\u0026nbsp;guidelines\u0026nbsp;[36]). Articles with significant methodological flaws or biases that could have compromised the validity of findings. Studies that focused primarily on non-human subjects or in vitro experiments without direct application to human cases. Research that did not address the specified outcomes of interest or failed to provide relevant data. Studies that lacked sufficient detail for extraction of relevant parameters or outcomes. Articles that did not clearly define Pesticide Exposure and Bone Tumors cases or relevant epidemiological metrics. A search strategy based on the PRISMA 2020 statement was used to find relevant studies. A total of 1670 article titles were obtained using the mentioned keywords and search strategy. After removing 320 duplicate titles with EndNote software, 1350 articles remained. Abstracts were then reviewed, resulting in the exclusion of 1040 abstracts. The full text of the remaining 310 articles was examined, leading to the exclusion of 290 articles not related to the study objectives. Finally, 20 articles were selected for inclusion in the study (Diagram 1). Each of the selected studies was reviewed separately by researchers and categorized into approved articles, rejected articles, and articles for re-examination. Researchers exchanged files for review, and joint review of selected articles and approved articles was conducted according to the PRISMA 2020 protocol. The quality of the articles was evaluated using the PRISMA 2020 statement, and they were indexed in valid databases.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eCharacteristics of Included Studies\u003c/p\u003e\n\u003cp\u003eThe characteristics of included studies are summarized in Table 1:\u003c/p\u003e\n\u003cp\u003eTable 1:\u0026nbsp;The characteristics of the included studies\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFindings on Pesticide Exposure and Bone Tumors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOsteosarcoma\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe findings indicate that individuals with a history of pesticide use are at a higher risk for developing a specific type of bone cancer known as osteosarcoma. This association clearly indicates that exposure to these chemicals can be considered a significant risk factor for the onset of this particular cancer [37, 38]. The findings indicate that agricultural workers who are exposed to pesticides are at a heightened risk of developing osteosarcoma. This association suggests a significant link between pesticide exposure and the likelihood of developing this particular form of cancer [37-39]. The findings from the study regarding organophosphate exposure indicate a significant association between this type of pesticide and the risk of developing osteosarcoma. Specifically, the results suggest that individuals who have been exposed to organophosphate pesticides are at a heightened risk for this particular bone cancer [40, 41].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEwing's Sarcoma\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe findings indicate that household pesticide is associated with an increased risk of developing certain health issues among boys aged 15 years and younger. This connection indicates that exposure to pesticides used in home processes may pose significant health risks for children, particularly young boys\u0026nbsp;[42, 43]. The findings indicate that agricultural workers have an increased risk of developing Ewing's sarcoma compared to non-agricultural workers. This association suggests that certain occupational exposures related to farming may contribute to the development of this specific type of cancer\u0026nbsp;[44, 45]. The findings indicated that children living near agricultural fields treated with pesticides had higher incidences of Ewing's sarcoma\u0026nbsp;[45, 46].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGeographical Variations\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe findings indicate that heavy pesticide use in rural areas is associated with an increased risk of bone cancer among males. This association highlights the potential impact of local agricultural practices on cancer incidence rates, particularly in regions where pesticide application is prevalent. The findings suggest that individuals living in rural areas, where pesticides are heavily utilized for agricultural purposes, may be at a greater risk of developing bone cancer\u0026nbsp;[37, 38].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParental Occupational Exposure\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe findings indicate that children whose fathers worked in agriculture have a significantly higher risk of developing Ewing's sarcoma. This suggests that parental occupational exposure, particularly in agricultural settings, may have lasting effects on children's health. The elevated risk for Ewing's sarcoma among children with fathers in agricultural occupations points to potential environmental and chemical exposures associated with farming. Agricultural work often involves the use of various pesticides and herbicides, which may contribute to increased cancer risk in offspring. Additionally, exposure to organic dust and other agricultural materials could also play a role in this association [44, 45, 47].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSpecific Pesticides\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe results indicate that organophosphates have frequently been identified as potentially carcinogenic agents linked to both osteosarcoma and Ewing's sarcoma. Studies indicate that exposure to these chemicals, commonly used in agricultural practices, may contribute to an increased risk of developing these types of bone cancers. The mechanisms by which organophosphates may induce carcinogenic effects include DNA damage, oxidative stress, and disruption of hormonal functions, all of which can lead to tumorigenesis [46, 48]. The results indicate that organochlorines are also associated with an increased risk for osteosarcoma. A pooled analysis indicated a significant association, pointing to the potential role of these chemicals in the development of this specific type of bone cancer. Organochlorines, like organophosphates, may exert their effects through similar biological mechanisms, including endocrine disruption and genotoxicity [49, 50].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMechanisms Explored\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe findings regarding the carcinogenic potential of pesticides highlight several biological mechanisms through which these chemicals may contribute to cancer development. One significant mechanism is genotoxicity, where certain pesticides cause DNA damage, leading to mutations that can initiate tumor formation. This DNA damage can disrupt normal cellular processes and promote uncontrolled cell growth. Additionally, pesticides can act as endocrine disruptors, interfering with hormonal pathways that regulate cell growth and differentiation. This disruption may lead to abnormal cellular proliferation, further increasing cancer risk. Lastly, pesticides may also modulate immune function, impairing the body’s ability to detect and eliminate cancerous cells, thereby facilitating tumor development [51-53].\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePesticides, designed to protect crops and control pests, have become ubiquitous in our modern world. While their use has undoubtedly increased agricultural productivity, their potential impact on human health, particularly cancer development, is increasingly recognized. This paper delves into the epidemiological evidence linking pesticide exposure to specific types of cancer, exploring the mechanisms involved and highlighting the need for further research and preventative measures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePesticide Exposure and Osteosarcoma: A Growing Concern\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOsteosarcoma, a malignant bone cancer that primarily affects adolescents and young adults, has been associated with a history of pesticide exposure. Research consistently indicates a higher incidence of osteosarcoma among individuals with a history of pesticide use, particularly among agricultural workers exposed to organophosphates and organochlorines. For example, numerous studies have found a significant association between pesticide exposure and the risk of osteosarcoma, especially in males. These findings conclude that exposure to pesticides significantly increases the likelihood of developing osteosarcoma [37-39, 54].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGeographical variations\u003c/strong\u003e also highlight the impact of pesticide use on cancer incidence. studies revealed a higher incidence of osteosarcoma in rural areas with heavy pesticide application, suggesting a strong correlation between agricultural practices and cancer risk [37, 38].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEwing's Sarcoma: A Potential Link to Pesticide Exposure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEwing's sarcoma, a rare and aggressive bone cancer, also shows a significant association with pesticide exposure. Children living near agricultural fields treated with pesticides have a higher incidence of Ewing's sarcoma, suggesting a potential link between environmental exposure and the development of this cancer. A study found a statistically significant association between pesticide exposure and Ewing's sarcoma risk, particularly in children [42]. Furthermore, another study also revealed that children whose fathers worked in agriculture have a significantly higher risk of developing Ewing's sarcoma, indicating a potential transgenerational effect of pesticide exposure [43].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSpecific Pesticides: A Focus on Organophosphates and Organochlorines\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOrganophosphates and organochlorines are frequently identified as potential carcinogens linked to both osteosarcoma and Ewing's sarcoma. These chemicals, commonly used in agricultural practices, can contribute to an increased risk of developing these cancers through mechanisms such as DNA damage, oxidative stress, and disruption of hormonal functions [16, 55]. Research has consistently shown that exposure to organophosphates can lead to significant health risks. For instance, studies indicate that these pesticides can cause genotoxic effects, resulting in mutations that initiate tumor formation. Additionally, organophosphates have been linked to oxidative stress, which can exacerbate cellular damage and promote cancer development. The endocrine-disrupting properties of these chemicals also play a critical role, as they interfere with hormonal pathways that regulate cell growth and differentiation, potentially leading to abnormal cellular proliferation [56-58]. Moreover, the implications of pesticide exposure extend beyond direct agricultural workers to their families and communities. Children living near agricultural fields treated with these chemicals may face increased risks of developing Ewing's sarcoma due to environmental exposure. This highlights the need for comprehensive public health strategies aimed at reducing pesticide use and promoting safer agricultural practices [49, 50]. Given the growing body of evidence linking pesticide exposure to various cancers, it is imperative that regulatory agencies reassess the safety of these chemicals and implement stricter guidelines to protect vulnerable populations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePublic Health Implications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGiven these findings:\u003c/strong\u003e\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eThere is a pressing need for stricter regulations regarding pesticide use in agriculture due to their potential carcinogenic effects.\u003c/li\u003e\n \u003cli\u003ePublic health initiatives should focus on educating agricultural workers about safe handling practices when using pesticides.\u003c/li\u003e\n \u003cli\u003eMonitoring programs should be implemented in high-exposure areas to assess environmental contamination levels regularly.\u003c/li\u003e\n \u003cli\u003eCommunity awareness campaigns could help inform residents about potential risks associated with living near agricultural areas where pesticides are used extensively.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhile this review provides valuable insights into associations between pesticide exposure and bone tumors:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eHeterogeneity among included studies regarding population characteristics limits generalizability.\u003c/li\u003e\n \u003cli\u003eMany studies relied on self-reported data regarding pesticide use which may introduce recall bias.\u003c/li\u003e\n \u003cli\u003eConfounding factors such as genetic predisposition or lifestyle choices were not always adequately controlled across all analyses.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eRecommendations for Future Research\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFuture research should focus on longitudinal designs assessing cumulative pesticide exposures over time while controlling for confounding factors such as genetic predisposition or lifestyle choices:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eInvestigate specific types/classes within broader categories like organophosphates or carbamates regarding their individual impacts on tumor development.\u003c/li\u003e\n \u003cli\u003eConduct biomonitoring assessments alongside epidemiological surveys assessing both environmental levels as well as biological markers indicative of exposure within affected populations.\u003c/li\u003e\n \u003cli\u003eExplore potential interactions between genetic susceptibility markers related specifically toward cancers like osteosarcoma/Ewing’s sarcoma alongside environmental exposures from pesticides utilized during critical developmental windows in childhood/adolescence.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe findings regarding pesticide exposure and its association with bone tumors, specifically osteosarcoma and Ewing\u0026apos;s sarcoma, reveal significant public health concerns. The evidence indicates that individuals with a history of pesticide use, particularly agricultural workers, face an increased risk of developing osteosarcoma. This suggests that exposure to pesticides, especially organophosphates and organochlorines, serves as a critical risk factor for this type of cancer. The mechanisms through which these pesticides may induce carcinogenic effects include DNA damage, oxidative stress, and disruption of hormonal functions, all of which can contribute to tumorigenesis. Moreover, the findings highlight the increased risk of Ewing\u0026apos;s sarcoma among children, particularly those whose fathers work in agriculture or who live near treated agricultural fields. This connection underscores the potential long-term health impacts of parental occupational exposure on children. The elevated incidence of Ewing\u0026apos;s sarcoma in these populations points to the importance of considering environmental and chemical exposures associated with farming practices. Young boys are particularly vulnerable to these risks, suggesting that household pesticide use may also contribute to adverse health outcomes in pediatric populations. Geographical variations in pesticide use further complicate the issue. The data indicate that heavy pesticide application in rural areas correlates with higher rates of bone cancer among males. This association emphasizes the influence of local agricultural practices on cancer incidence rates and highlights the necessity for targeted public health strategies in regions where pesticide use is prevalent. Understanding these geographical disparities can inform interventions aimed at reducing exposure and mitigating health risks for affected communities. The evidence linking pesticide exposure to an increased risk of osteosarcoma and Ewing\u0026apos;s sarcoma necessitates urgent action from public health officials and policymakers. Comprehensive strategies should be developed to educate agricultural workers and their families about the risks associated with pesticide use, promote safer pest management practices, and implement stricter regulations on harmful chemicals. Continued research is essential to further elucidate the mechanisms by which pesticides contribute to cancer development and to ensure protective measures are in place for vulnerable populations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in the study involving human participants were by the ethical standards of the institutional and national research committee and with the 1975 Helsinki Declaration and its later amendments or comparable ethical standards.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest, financial or\u0026nbsp;otherwise.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\"OSA, GS, RM, MK, RR, and HH analyzed and interpreted the data. SD, RR contributor in writing the manuscript. All authors read and approved the final manuscript.\"\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRaman S: \u003cstrong\u003eAgricultural sustainability: principles, processes, and prospects\u003c/strong\u003e: CRC Press; 2024.\u003c/li\u003e\n\u003cli\u003eBellwood P: \u003cstrong\u003eFirst farmers: the origins of agricultural societies\u003c/strong\u003e: John Wiley \u0026amp; Sons; 2023.\u003c/li\u003e\n\u003cli\u003eByerlee D, De Janvry A, Sadoulet E: \u003cstrong\u003eAgriculture for development: Toward a new paradigm\u003c/strong\u003e. \u003cem\u003eAnnu Rev Resour Econ \u003c/em\u003e2009, \u003cstrong\u003e1\u003c/strong\u003e(1):15-31.\u003c/li\u003e\n\u003cli\u003eKlerkx L, Van Mierlo B, Leeuwis C: \u003cstrong\u003eEvolution of systems approaches to agricultural innovation: concepts, analysis and interventions\u003c/strong\u003e. \u003cem\u003eFarming Systems Research into the 21st century: The new dynamic \u003c/em\u003e2012:457-483.\u003c/li\u003e\n\u003cli\u003eHorrigan L, Lawrence RS, Walker P: \u003cstrong\u003eHow sustainable agriculture can address the environmental and human health harms of industrial agriculture\u003c/strong\u003e. \u003cem\u003eEnvironmental health perspectives \u003c/em\u003e2002, \u003cstrong\u003e110\u003c/strong\u003e(5):445-456.\u003c/li\u003e\n\u003cli\u003eNicolopoulou-Stamati P, Maipas S, Kotampasi C, Stamatis P, Hens L: \u003cstrong\u003eChemical pesticides and human health: the urgent need for a new concept in agriculture\u003c/strong\u003e. \u003cem\u003eFrontiers in public health \u003c/em\u003e2016, \u003cstrong\u003e4\u003c/strong\u003e:148.\u003c/li\u003e\n\u003cli\u003eSabarwal A, Kumar K, Singh RP: \u003cstrong\u003eHazardous effects of chemical pesticides on human health\u0026ndash;Cancer and other associated disorders\u003c/strong\u003e. \u003cem\u003eEnvironmental toxicology and pharmacology \u003c/em\u003e2018, \u003cstrong\u003e63\u003c/strong\u003e:103-114.\u003c/li\u003e\n\u003cli\u003eBonner MR, Freeman LEB, Hoppin JA, Koutros S, Sandler DP, Lynch CF, Hines CJ, Thomas K, Blair A, Alavanja MC: \u003cstrong\u003eOccupational exposure to pesticides and the incidence of lung cancer in the agricultural health study\u003c/strong\u003e. \u003cem\u003eEnvironmental health perspectives \u003c/em\u003e2017, \u003cstrong\u003e125\u003c/strong\u003e(4):544-551.\u003c/li\u003e\n\u003cli\u003eNayak P, Solanki H: \u003cstrong\u003ePesticides and Indian agriculture\u0026mdash;a review\u003c/strong\u003e. \u003cem\u003eInt J Res Granthaalayah \u003c/em\u003e2021, \u003cstrong\u003e9\u003c/strong\u003e(5):250-263.\u003c/li\u003e\n\u003cli\u003eCouncil NR, Sciences CoL, Studies BoE, Agriculture CotFRoPiU: \u003cstrong\u003eThe future role of pesticides in US agriculture\u003c/strong\u003e: National Academies Press; 2000.\u003c/li\u003e\n\u003cli\u003eSharma N, Singhvi R: \u003cstrong\u003eEffects of chemical fertilizers and pesticides on human health and environment: a review\u003c/strong\u003e. \u003cem\u003eInternational journal of agriculture, environment and biotechnology \u003c/em\u003e2017, \u003cstrong\u003e10\u003c/strong\u003e(6):675-680.\u003c/li\u003e\n\u003cli\u003eKoutros S, Beane Freeman LE, Lubin JH, Heltshe SL, Andreotti G, Barry KH, DellaValle CT, Hoppin JA, Sandler DP, Lynch CF: \u003cstrong\u003eRisk of total and aggressive prostate cancer and pesticide use in the Agricultural Health Study\u003c/strong\u003e. \u003cem\u003eAmerican journal of epidemiology \u003c/em\u003e2013, \u003cstrong\u003e177\u003c/strong\u003e(1):59-74.\u003c/li\u003e\n\u003cli\u003eCurl CL, Spivak M, Phinney R, Montrose L: \u003cstrong\u003eSynthetic pesticides and health in vulnerable populations: agricultural workers\u003c/strong\u003e. \u003cem\u003eCurrent environmental health reports \u003c/em\u003e2020, \u003cstrong\u003e7\u003c/strong\u003e:13-29.\u003c/li\u003e\n\u003cli\u003eAndreotti G, Hou L, Beane Freeman LE, Mahajan R, Koutros S, Coble J, Lubin J, Blair A, Hoppin JA, Alavanja M: \u003cstrong\u003eBody mass index, agricultural pesticide use, and cancer incidence in the Agricultural Health Study cohort\u003c/strong\u003e. \u003cem\u003eCancer Causes \u0026amp; Control \u003c/em\u003e2010, \u003cstrong\u003e21\u003c/strong\u003e:1759-1775.\u003c/li\u003e\n\u003cli\u003eCarozza SE, Li B, Wang Q, Horel S, Cooper S: \u003cstrong\u003eAgricultural pesticides and risk of childhood cancers\u003c/strong\u003e. \u003cem\u003eInternational journal of hygiene and environmental health \u003c/em\u003e2009, \u003cstrong\u003e212\u003c/strong\u003e(2):186-195.\u003c/li\u003e\n\u003cli\u003eRoh T, Aggarwal A, Hasan NT, Upadhyay A, Trisha NF: \u003cstrong\u003ePesticides and Cancer\u003c/strong\u003e. 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\u003cstrong\u003ePesticides, gene polymorphisms, and bladder cancer among Egyptian agricultural workers\u003c/strong\u003e. \u003cem\u003eArchives of environmental \u0026amp; occupational health \u003c/em\u003e2015, \u003cstrong\u003e70\u003c/strong\u003e(1):19-26.\u003c/li\u003e\n\u003cli\u003eCavalier H, Trasande L, Porta M: \u003cstrong\u003eExposures to pesticides and risk of cancer: evaluation of recent epidemiological evidence in humans and paths forward\u003c/strong\u003e. \u003cem\u003eInternational journal of cancer \u003c/em\u003e2023, \u003cstrong\u003e152\u003c/strong\u003e(5):879-912.\u003c/li\u003e\n\u003cli\u003eThakur J, Rao B, Rajwanshi A, Parwana H, Kumar R: \u003cstrong\u003eEpidemiological study of high cancer among rural agricultural community of Punjab in Northern India\u003c/strong\u003e. \u003cem\u003eInternational journal of environmental research and public health \u003c/em\u003e2008, \u003cstrong\u003e5\u003c/strong\u003e(5):399-407.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Bone Tumor, cancer, pesticide, human, health, public health, osteosarcoma, Ewing's sarcoma","lastPublishedDoi":"10.21203/rs.3.rs-6369910/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6369910/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Pesticides are widely used in agriculture, but their potential adverse effects on human health, particularly concerning cancer risk, have raised significant public health concerns. This systematic review evaluates the association between pesticide exposure and the incidence of bone tumors, specifically osteosarcoma and Ewing's sarcoma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e: To systematically review and synthesize the available evidence on the relationship between pesticide exposure and the risk of developing bone tumors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This systematic review was conducted in the winter of 2024 by searching keywords such as \"pesticide exposure,\" \"bone tumors,\" \"osteosarcoma,\" \"Ewing's sarcoma,\" \"agriculture,\" \"cancer risk,\" and \"environmental exposure\" in PubMed, Google Scholar databases, ISC, Scopus, and Web of Science without time limits. The search strategy was based on the PRISMA 2020 statement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: A total of 20 studies met the inclusion criteria. The findings suggest a significant association between pesticide exposure and an increased risk of both osteosarcoma and Ewing's sarcoma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: This review highlights the need for stricter regulations on pesticide use in agriculture and further research to elucidate the mechanisms underlying these associations.\u003c/p\u003e","manuscriptTitle":"Pesticide Exposure and Bone Tumors: A Systematic Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-08 20:03:49","doi":"10.21203/rs.3.rs-6369910/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6e87bc85-39a6-4971-914c-70fee469c08b","owner":[],"postedDate":"May 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-10T13:24:02+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-08 20:03:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6369910","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6369910","identity":"rs-6369910","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}