Glyphosate and Non-Hodgkin lymphoma: No causal relationship
Abstract
Objective: Herbicides are used worldwide by both residential and agricultural users. Due to the statistical analysis of some epidemiologic studies the International Agency for Research on Cancer classified the broad-spectrum herbicide Glyphosate (GS) in 2015, as potentially carcinogenic to humans especially with respect to non-Hodgkin lymphoma (NHL). In this systematic review and re-analysis, the relationship between Glyphosate and NHL was re- investigated.
Methods: A systematic review and re-analysis of studies which investigated the relationship between GS and NHL was conducted. The method of the conditio sine qua non relationship, the method of the conditio per quam relationship, the method of the exclusion relationship and the mathematical formula of the causal relationship k were used to proof the hypothesis. Significance was indicated by a p-value of less than 0.05.
Results: The studies analyzed do not provide any direct and indirect evidence that NHL is caused GS.
Conclusion: In this re-analysis, no causal relationship was apparent between Glyphosate and NHL and its subtypes.
Keywords: Glyphosate, Non-Hodgkin lymphoma, no causal relationship
Keywords:
Glyphosate, Non-Hodgkin lymphoma, no causal relationshipDOI
https://doi.org/10.22270/jddt.v10i1-s.3856References
Malpighi M. De viscerum structura exercitatio anatomica.Accedit dissertatio eiusdem De polypo cordis, Bononiae: Iacobi Montij; 1666. doi: https://doi.org/10.3931/e-rara-23974
Hodgkin T. On some Morbid Appearances of the Absorbent Glands and Spleen, Medico-Chir Trans, 1832; 17:68-114. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2116706/.
Wilks S. Cases with enlargement of the lymphatic glands and spleen (or Hodgkin’s disease) with remarks, Guys Hosp Rep, 1865.
Armitage JO, Gascoyne RD, Lunning MA, Cavalli F. Non-Hodgkin lymphoma, Lancet Lond Engl, 2017; 390(10091):298-310. doi: https://doi.org/10.1016/S0140-6736(16)32407-2 [PMID: 28153383]
Virchow R. Weisses Blut. Neue Notizen aus dem Gebiet der Naturfund Heilkunde, Florieps Neue Not, 1845; 36:151. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2116706/.
Bennett JH. Two cases of disease and enlargement of thespleen in which death took place from the presence of purulentmatter in the blood, Edinb Med Surg J, 1845; 64:413-423. https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2141.2000.01988.x.
Cohnheim P. Ein Fall von Pseudoleukämie, Arch Für Pathol Anat Physiol Für Klin Med, 1865; 33(3):451-454. doi: https://doi.org/10.1007/BF02137492
Rappaport H. Tumors of the Hematopoietic System, Washington: Armed Forces Institute of Pathology; 1966. http://annals.org/article.aspx?doi=10.7326/0003-4819-67-3-686_2. Accessed May 15, 2019.
IARC WG on the E of CR to H. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 112, Vol 112. ; 2017.
EPA US. U.S. Environmental Protection Agency Reregistration Eligibility Decision (RED) Glyphosate, Environ Prot Agency Wash DCUS, 1993; EPA-738-R-93-014.
Williams GM, Kroes R, Munro IC. Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans, Regul Toxicol Pharmacol RTP, 2000; 31(2 Pt 1):117-165. doi: https://doi.org/10.1006/rtph.1999.1371 [PMID: 10854122]
Steinrücken HC, Amrhein N. The herbicide glyphosate is a potent inhibitor of 5-enolpyruvyl-shikimic acid-3-phosphate synthase, Biochem Biophys Res Commun, 1980; 94(4):1207-1212. [PMID: 7396959]
Bolognesi C, Bonatti S, Degan P, et al. Genotoxic Activity of Glyphosate and Its Technical Formulation Roundup, J Agric Food Chem, 1997; 45(5):1957-1962. doi: https://doi.org/10.1021/jf9606518
Daruich J, Zirulnik F, Gimenez MS. Effect of the herbicide glyphosate on enzymatic activity in pregnant rats and their fetuses, Environ Res, 2001; 85(3):226-231. doi: https://doi.org/10.1006/enrs.2000.4229 [PMID: 11237511]
El-Demerdash FM, Yousef MI, Elagamy EI. Influence of paraquat, glyphosate, and cadmium on the activity of some serum enzymes and protein electrophoretic behavior (in vitro), J Environ Sci Health B, 2001; 36(1):29-42. [PMID: 11281253]
Hietanen E, Linnainmaa K, Vainio H. Effects of phenoxyherbicides and glyphosate on the hepatic and intestinal biotransformation activities in the rat, Acta Pharmacol Toxicol (Copenh), 1983; 53(2):103-112. [PMID: 6624478]
Lioi MB, Scarfì MR, Santoro A, et al. Genotoxicity and oxidative stress induced by pesticide exposure in bovine lymphocyte cultures in vitro, Mutat Res, 1998; 403(1-2):13-20. [PMID: 9726001]
Olorunsogo OO, Bababunmi EA, Bassir O. Effect of glyphosate on rat liver mitochondria in vivo, Bull Environ Contam Toxicol, 1979; 22(3):357-364. [PMID: 223703]
Peluso M, Munnia A, Bolognesi C, Parodi S. 32P-postlabeling detection of DNA adducts in mice treated with the herbicide Roundup, Environ Mol Mutagen, 1998; 31(1):55-59. [PMID: 9464316]
Walsh LP, McCormick C, Martin C, Stocco DM. Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression, Environ Health Perspect, 2000; 108(8):769-776. doi: https://doi.org/10.1289/ehp.00108769 [PMID: 10964798] [PMCID: PMC1638308]
Yousef MI, Salem MH, Ibrahim HZ, Helmi S, Seehy MA, Bertheussen K. Toxic effects of carbofuran and glyphosate on semen characteristics in rabbits, J Environ Sci Health B, 1995; 30(4):513-534. doi: https://doi.org/10.1080/03601239509372951 [PMID: 7797819]
Pearson K. On the Theory of Contingency and Its Relation to Association and Normal Correlation, London: Dulau and Co.; 1904.
Fisher RA. On the Interpretation of χ 2 from Contingency Tables, and the Calculation of P, J R Stat Soc, 1922; 85(1):87. doi: https://doi.org/10.2307/2340521
Bortz J, Lienert GA, Boehnke K. Verteilungsfreie Methoden in der Biostatistik: mit 247 Tabellen, Berlin: Springer; 1990.
Scheid H. Wahrscheinlichkeitsrechnung, Vol 6. Mannheim: BI-Wiss.-Verl.; 1992.
Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration, PLoS Med, 2009; 6(7):1000100. doi: https://doi.org/10.1371/journal.pmed.1000100 [PMID: 19621070]
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement, Open Med Peer-Rev Indep Open-Access J, 2009; 3(3):123-130. [PMID: 21603045]
Hardell L, Eriksson M. A case-control study of non-Hodgkin lymphoma and exposure to pesticides, Cancer, 1999; 85(6):1353-1360. [PMID: 10189142]
Leon ME, Schinasi LH, Lebailly P, et al. Pesticide use and risk of non-Hodgkin lymphoid malignancies in agricultural cohorts from France, Norway and the USA: a pooled analysis from the AGRICOH consortium, Int J Epidemiol, 18 2019. doi: https://doi.org/10.1093/ije/dyz017 [PMID: 30880337]
Barukčić I. Die Kausalität, 1. Aufl. Hamburg: Wiss.-Verl.; 1989.
Barukčić I. Die Kausalität, 2., völlig überarb. Aufl. Wilhelmshaven: Scientia; 1997.
Barukčić I. The Mathematical Formula of the Causal Relationship k, Int J Appl Phys Math, 2016; 6(2):45-65. doi: https://doi.org/10.17706/ijapm.2016.6.2.45-65
Barukčić I. Unified Field Theory, J Appl Math Phys, 2016; 04(08):1379-1438. doi: https://doi.org/10.4236/jamp.2016.48147
Barukčić I. Die Kausalität, Reprint of first Edition 1989. Norderstedt: Books on Demand; 2017.
Barukčić I. Epstein-barr virus is the cause of multiple sclerosis, Int J Curr Med Pharm Res, 2018; 4(9 (A)):3674-3682. doi: https://doi.org/10.24327/23956429.ijcmpr20180538
Barukčić I. Smoking of tobacco is the cause of human lung cancer, J Drug Deliv Ther, 2019; 9(1-s):148-160. doi: https://doi.org/10.22270/jddt.v9i1-s.2273
Barukčić K, Barukčić I. Epstein Barr Virus—The Cause of Multiple Sclerosis, J Appl Math Phys, 2016; 04(06):1042-1053. doi: https://doi.org/10.4236/jamp.2016.46109
Hessen J. Das Kausalprinzip, Augsburg: Filser; 1928.
Korch H. Das Problem Der Kausalität, Berlin: Dt. Verlag der Wissenschaften; 1965.
Barukčić I. Helicobacter Pylori is the Cause of Gastric Cancer, Mod Health Sci, 2018; 1(1):43-50. doi: https://doi.org/10.30560/mhs.v1n1p43
Barukčić K, Barukčić JP, Barukčić I. Epstein-Barr virus is the cause of rheumatoid arthritis, Romanian J Rheumatol, 2018; 27(4):148-163. https://view.publitas.com/amph/rjr_2018_4_art-02/page/1. Accessed December 29, 2018.
Uspensky J v. Introduction To Mathematical Probability, New York (USA): McGraw-Hill Company; 1937.
Pearson K. X. On the criterion that a given system of deviations from the probable in the case of a correlated system of variables is such that it can be reasonably supposed to have arisen from random sampling, Lond Edinb Dublin Philos Mag J Sci, 1900; 50(302):157-175.
Barukčić I. Human Papillomavirus—The Cause of Human Cervical Cancer, J Biosci Med, 2018; 06(04):106-125. doi: https://doi.org/10.4236/jbm.2018.64009
Barukčić I. Statins and death due to any cause – all doubts removed?, Int J Curr Sci Res, 2019; 5(12):1884-1911.
Barukčić I. Index of Unfairness, Mod Health Sci, 2019; 2(1):p22. doi: https://doi.org/10.30560/mhs.v2n1p22
Barukčić I. Index of Independence, Mod Health Sci, 2019; 2(2):1-25. doi: https://doi.org/10.30560/mhs.v2n2p1
McDuffie HH, Pahwa P, McLaughlin JR, et al. Non-Hodgkin’s lymphoma and specific pesticide exposures in men: cross-Canada study of pesticides and health, Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol, 2001; 10(11):1155-1163. [PMID: 11700263]
Barukčić I. The P Value of likely extreme events, Int J Curr Sci Res, 2019; 5(11):1841-1861. http://www.drbgrpublications.in/ijcsr-179-The-P-Value-of-likely-extreme-events-Ilija-Baruk%C4%8Di%C4%87.pdf.
Hardell L, Eriksson M, Nordstrom M. Exposure to pesticides as risk factor for non-Hodgkin’s lymphoma and hairy cell leukemia: pooled analysis of two Swedish case-control studies, Leuk Lymphoma, 2002; 43(5):1043-1049. [PMID: 12148884]
De Roos AJ, Zahm SH, Cantor KP, et al. Integrative assessment of multiple pesticides as risk factors for non-Hodgkin’s lymphoma among men, Occup Environ Med, 2003; 60(9):E11. doi: https://doi.org/10.1136/oem.60.9.e11 [PMID: 12937207] [PMCID: PMC1740618]
Cantor KP. Farming and mortality from non-Hodgkin’s lymphoma: a case-control study, Int J Cancer, 1982; 29(3):239-247. [PMID: 7040259]
De Roos AJ, Blair A, Rusiecki JA, et al. Cancer incidence among glyphosate-exposed pesticide applicators in the Agricultural Health Study, Environ Health Perspect, 2005; 113(1):49-54. doi: https://doi.org/10.1289/ehp.7340 [PMID: 15626647] [PMCID: PMC1253709]
Eriksson M, Hardell L, Carlberg M, Akerman M. Pesticide exposure as risk factor for non-Hodgkin lymphoma including histopathological subgroup analysis, Int J Cancer, 2008; 123(7):1657-1663. doi: https://doi.org/10.1002/ijc.23589 [PMID: 18623080]
Orsi L, Delabre L, Monnereau A, et al. Occupational exposure to pesticides and lymphoid neoplasms among men: results of a French case-control study, Occup Environ Med, 2009; 66(5):291-298. doi: https://doi.org/10.1136/oem.2008.040972 [PMID: 19017688] [PMCID: PMC2728754]
Andreotti G, Koutros S, Hofmann JN, et al. Glyphosate Use and Cancer Incidence in the Agricultural Health Study, J Natl Cancer Inst, 2018; 110(5):509-516. doi: https://doi.org/10.1093/jnci/djx233 [PMID: 29136183] [PMCID: PMC6279255]
IARC WG on the E of CR to H. Biological agents. Volume 100 B. A review of human carcinogens., Iarc Monogr Eval Carcinog Risks Hum, 2012; 100(PT B):1-441. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4781184/. Accessed May 19, 2019. [PMID: 23189750] [PMCID: PMC4781184]
Teras LR, Rollison DE, Pawlita M, et al. Epstein-Barr virus and risk of non-Hodgkin lymphoma in the cancer prevention study-II and a meta-analysis of serologic studies, Int J Cancer, 2015; 136(1):108-116. doi: https://doi.org/10.1002/ijc.28971 [PMID: 24831943]
National Cancer Institute NI of H. Non-Hodgkin Lymphoma - Cancer Stat Facts, Natl Cancer Inst - Surveill Epidemiloogy End Results Program, 2019; May 18. https://seer.cancer.gov/statfacts/html/nhl.html. Accessed May 18, 2019.
Sandlund JT. Non-Hodgkin Lymphoma in Children, Curr Hematol Malig Rep, 2015; 10(3):237-243. doi: https://doi.org/10.1007/s11899-015-0277-y [PMID: 26174528]
Chang ET, Delzell E. Systematic review and meta-analysis of glyphosate exposure and risk of lymphohematopoietic cancers, J Environ Sci Health B, 2016; 51(6):402-434. doi: https://doi.org/10.1080/03601234.2016.1142748 [PMID: 27015139] [PMCID: PMC4866614]
Zhang L, Rana I, Taioli E, Shaffer R, Sheppard L. Exposure to Glyphosate-Based Herbicides and Risk for Non-Hodgkin Lymphoma: A Meta-Analysis and Supporting Evidence, Mutat Res Mutat Res, February 2019. doi: https://doi.org/10.1016/j.mrrev.2019.02.001
Published
Abstract Display: 985 
PDF Downloads: 647 How to Cite
Issue
Section
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
How to Cite
.