Cancer Causes & Control

, Volume 18, Issue 5, pp 457–478 | Cite as

A systematic review of myeloid leukemias and occupational pesticide exposure

  • Geneviève Van Maele-Fabry
  • Sophie Duhayon
  • Dominique Lison
Original Paper



To conduct a systematic review and meta-analyses of published studies examining the association between myeloid leukemias (ML) and occupational pesticide exposure.


Studies were identified from a MEDLINE search through 31 May 2006 and from the reference lists of identified publications. Studies were summarized and evaluated for publication bias. Relative risk estimates for ML were extracted from 17 cohort and 16 case–control studies published between 1979 and 2005. Fixed- or random-effect meta-analysis models were used depending on the presence of heterogeneity between studies. Separate analyses were conducted after stratification for study design, occupational group, ML subtype or gender.


The overall meta-rate ratio estimate (meta-RR) for the cohort studies was 1.21 (95% confidence interval [CI] 0.99–1.48). Substantial heterogeneity existed among cohort studies (p = 1.064 × 10−5), mainly reflecting the varying occupational categories examined. The meta-RR was 6.32 (95% CI: 1.90–21.01) for manufacturing workers and 2.14 (95% CI: 1.39–3.31) for pesticide applicators. After stratification of cohort studies by specific ML subtype, an increased risk of acute myeloid leukemia (AML) was found (meta-RR: 1.55; 95% CI: 1.02–2.34). No significant heterogeneity was detected among case–control studies and an increased risk of chronic myeloid leukemia (CML) was found among men (meta-RR: 1.39; 95% CI: 1.03–1.88) and farmers or agricultural workers (meta-RR: 1.38; 95% CI: 1.06–1.79).


The strongest evidence of an increased risk of ML comes from manufacturing workers and pesticide applicators. Further studies will be needed to correlate reliable exposure data within these specific occupational groups with well-defined subtypes of leukemia to refine this assessment.


Meta-analysis Myeloid leukemia Pesticides Occupation Risk 



V.M.F.G. was supported by a grant from the Belgian Ministry of Health (Grant Number 95/15 (164)).


  1. 1.
    Lee GR, Foerster J, Lukens J, Paraskevas F, Greer JP, Rodgers GM (1999) Wintrobe’s clinical hematology (Hardcover), 10th edn. Lippincott Williams & Wilkins, 2764 ppGoogle Scholar
  2. 2.
    Beers MH, Berkow R (1999) Leukemias. The Merck manual of diagnosis and therapy, 17th edn. Merck & Co. Inc., Merck Research Laboratories, Whitehouse Station, NJ, USAGoogle Scholar
  3. 3.
    Vardiman JW, Harris NL, Brunning RD (2002) The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 100:2292–2302PubMedCrossRefGoogle Scholar
  4. 4.
    Zeeb H, Blettner M (1998) Adult leukaemia: what is the role of currently known risk factors?. Radiat Environ Biophys 36:217–228PubMedCrossRefGoogle Scholar
  5. 5.
    Greaves MF (1997) Aetiology of acute leukaemia. Lancet 349:344–349PubMedCrossRefGoogle Scholar
  6. 6.
    Linet MS, Cartwright RA (1996) The leukemias. In: Schottenfeld D, Fraumeni JF Jr (eds) Cancer epidemiology and prevention, 2nd edn. Oxford University Press, NewYork, NY, pp 841–879Google Scholar
  7. 7.
    Greaves MF (2004) Biological models for leukaemia and lymphoma. IARC Sci Publ 157:351–372PubMedGoogle Scholar
  8. 8.
    Schnatter AR, Rosamilia K, Wojcik NC (2005) Review of the literature on benzene exposure and leukemia subtypes. Chem Biol Interact 153–154:9–21PubMedCrossRefGoogle Scholar
  9. 9.
    Greenberg RS, Mandel J, Pastides H, Britton NL, Rudenko L, Starr TB (2001) A meta-analysis of cohort studies describing mortality and cancer incidence among chemical workers in the United States and Western Europe. Epidemiology 12:727–740PubMedCrossRefGoogle Scholar
  10. 10.
    Smith MT, Zhang L (1998) Biomarkers of leukemia risk: benzene as a model. Environ Health Perspect 106:937–946PubMedCrossRefGoogle Scholar
  11. 11.
    International Classification of Disease (1989). 10th revision.
  12. 12.
    Greenberg PL, Young NS, Gattermann N (2002) Myelodysplastic syndromes. Hematology (Am Soc Hematol Educ Program) 136–161Google Scholar
  13. 13.
    Breslow NE, Day NE (1987) Statistical methods in cancer research: the design and analysis of cohort studies. IARC scientific publications vol II, no 82. International Agency for Research on Cancer, LyonGoogle Scholar
  14. 14.
    Van Maele-Fabry G, Willems JL (2003) Occupation related pesticide exposure and cancer of the prostate: a meta-analysis. Occup Environ Med 60:634–642PubMedCrossRefGoogle Scholar
  15. 15.
    Clarke M, Oxman AD (eds) (2000) Cochrane reviewers’ handbook 4.1 (updated June 2000). In: Review Manager (RevMan) (computer program). Version 4.1. The Cochrane Collaboration 2000, Oxford, EnglandGoogle Scholar
  16. 16.
    Lipsett M, Campleman S (1999) Occupational exposure to diesel exhaust and lung cancer: a meta-analysis. Am J Public Health 89:1009–1017PubMedGoogle Scholar
  17. 17.
    Greenland S (1998) Meta-analysis. In: Rothman KJ, Greenland S (eds) Modern epidemiology, 2nd edn. Lippincott-Raven, Philadelphia, pp 643–673Google Scholar
  18. 18.
    Stewart RE, Dennis LK, Dawson DV, Resnick MI (1999) A meta-analysis of risk estimates for prostate cancer related to tire and rubber manufacturing operations. J Occup Environ Med 41:1079–1084PubMedCrossRefGoogle Scholar
  19. 19.
    Dennis LK (2000) Meta-analysis for combining relative risks of alcohol consumption and prostate cancer. Prostate 42:56–66PubMedCrossRefGoogle Scholar
  20. 20.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  21. 21.
    Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedGoogle Scholar
  22. 22.
    Olkin I (1994) Re: “A critical look at some popular meta-analytic methods”. Am J Epidemiol 140:297–299PubMedGoogle Scholar
  23. 23.
    Acquavella JF, Delzell E, Cheng H, Lynch CF, Johnson G (2004) Mortality and cancer incidence among alachlor manufacturing workers 1968–99. Occup Environ Med 61:680–685PubMedCrossRefGoogle Scholar
  24. 24.
    Asp S, Riihimaki V, Hernberg S, Pukkala E (1994) Mortality and cancer morbidity of Finnish chlorophenoxy herbicide applicators: an 18-year prospective follow-up. Am J Ind Med 26:243–253PubMedCrossRefGoogle Scholar
  25. 25.
    Beard J, Sladden T, Morgan G, Berry G, Brooks L, McMichael A (2003) Health impacts of pesticide exposure in a cohort of outdoor workers. Environ Health Perspect 111:724–730PubMedCrossRefGoogle Scholar
  26. 26.
    Blair A, Grauman DJ, Lubin JH, Fraumeni JF Jr (1983) Lung cancer and other causes of death among licensed pesticide applicators. J Natl Cancer Inst 71:31–37PubMedGoogle Scholar
  27. 27.
    Bucchi L, Nanni O, Ravaioli A, Falcini F, Ricci R, Buiatti E, Amadori D (2004) Cancer mortality in a cohort of male agricultural workers from northern Italy. J Occup Environ Med 46:249–256PubMedCrossRefGoogle Scholar
  28. 28.
    Bueno de Mesquita H, Doornbos G, Van der Kuip D, Kogevinas M, Winkelmann R (1993) Occupational exposure to phenoxy herbicides and chlorophenols and cancer mortality in The Netherlands. Am J Ind Med 23:289–300CrossRefGoogle Scholar
  29. 29.
    Cantor KP, Silberman W (1999) Mortality among aerial pesticide applicators and flight instructors: follow-up from 1965–1988. Am J Ind Med 36:239–247PubMedCrossRefGoogle Scholar
  30. 30.
    Dean G (1994) Deaths from primary brain cancers, lymphatic and hematopoietic cancers in Agricultural Workers in the Republic of Ireland. J Epidemiol Community Health 48:364–368PubMedCrossRefGoogle Scholar
  31. 31.
    Ji JG, Hemminki K (2005) Occurrences of leukemia subtypes by socioeconomic and occupational groups in Sweden. J Occup Environ Med 47:1131–1140PubMedCrossRefGoogle Scholar
  32. 32.
    Kelleher C, Newell J, MacDonagh-White C, MacHale E, Egan E, Connolly E, Gough H, Delaney B, Shryane E (1998) Incidence and occupational pattern of leukaemias, lymphomas, and testicular tumours in western Ireland over an 11 year period. J Epidemiol Community Health 52:651–656PubMedGoogle Scholar
  33. 33.
    Littorin M, Attewell R, Skerfving S, Horstmann V, Moller T (1993) Mortality and tumour morbidity among Swedish market gardeners and orchardists. Int Arch Occup Environ Health 65:163–169PubMedCrossRefGoogle Scholar
  34. 34.
    Nanni O, Ravaioli A, Bucchi L, Falcini F, Ricci R, Buiatti E, Amadori D (2005) Relative and absolute cancer mortality of women in agriculture in northern Italy. Eur J Cancer Prev 14:337–344PubMedCrossRefGoogle Scholar
  35. 35.
    Semenciw RM, Morrison HI, Morison D, Mao Y (1994) Leukemia mortality and farming in the Prairie Provinces of Canada. Can J Public Health 85:208–211PubMedGoogle Scholar
  36. 36.
    Sinner PJ, Cerhan JR, Folsom AR, Ross JA (2005) Positive association of farm or rural residence with acute myeloid leukemia incidence in a cohort of older women. Cancer Epidemiol Biomarkers Prev 14:2446–2448PubMedCrossRefGoogle Scholar
  37. 37.
    Sperati A, Rapiti E, Settimi L, Quercia A, Terenzoni B, Forastiere F (1999) Mortality among male licensed pesticide users and their wives. Am J Ind Med 36:142–146PubMedCrossRefGoogle Scholar
  38. 38.
    Stark AD, Chang HG, Fitzgerald EF, Riccardi K, Stone RR (1990) A retrospective cohort study of cancer incidence among New York State Farm Bureau members. Arch Environ Health 45:155–162PubMedCrossRefGoogle Scholar
  39. 39.
    t' Mannetje A, McLean S, Cheng S, Boffetta P, Colin D, and Pearce N (2005) Mortality in New Zealand workers exposed to phenoxy herbicides and dioxins. Occup Environ Med 62:34–40PubMedCrossRefGoogle Scholar
  40. 40.
    Adegoke OJ, Blair A, Shu XO, Sanderson M, Jin F, Dosemeci M, Addy CL, Zheng W (2003) Occupational history and exposure and the risk of adult leukemia in Shanghai. Ann Epidemiol 13:485–494PubMedCrossRefGoogle Scholar
  41. 41.
    Bjork J, Albin M, Welinder H, Tinnerberg H, Mauritzson N, Kauppinen T, Stromberg U, Johansson B, Billstrom R, Mikoczy Z, Ahlgren T, Nilsson PG, Mitelman F, Hagmar L (2001) Are occupational, hobby, or lifestyle exposures associated with Philadelphia chromosome positive chronic myeloid leukaemia? Occup Environ Med 58:722–727PubMedCrossRefGoogle Scholar
  42. 42.
    Blair A, Thomas TL (1979) Leukemia among Nebraska farmers: a death certificate study. Am J Epidemiol 110:264–273PubMedGoogle Scholar
  43. 43.
    Blair A, White DW (1981) Death certificate study of leukemia among farmers from Wisconsin. J Natl Cancer Inst 66:1027–1030PubMedGoogle Scholar
  44. 44.
    Brown LM, Blair A, Gibson R, Everett GD, Cantor KP, Schuman LM, Burmeister LF, Van Lier S, Dick F (1990) Pesticide exposures and other agricultural risk factors for leukemia among men in Iowa and Minnesota. Cancer Res 50:6585–6591PubMedGoogle Scholar
  45. 45.
    Brownson RC, Reif JS (1988) A cancer registry-based study of occupational risk for lymphoma, multiple myeloma and leukaemia. Int J Epidemiol 17:27–32PubMedCrossRefGoogle Scholar
  46. 46.
    Burmeister L, van Lier SF, Isacson P (1982) Leukemia and farm practices in Iowa. Am J Epidemiol 115:720–728PubMedGoogle Scholar
  47. 47.
    Ciccone G, Mirabelli D, Levis A, Gavarotti P, Rege CG, Davico L, Vineis P (1993) Myeloid leukemias and myelodysplastic syndromes: chemical exposure, histologic subtype and cytogenetics in a case–control study. Cancer Genet Cytogenet 68:135–139PubMedCrossRefGoogle Scholar
  48. 48.
    Flodin U, Fredrikson M, Persson B, Hardell L, Axelson O (1986) Background radiation, electrical work, and some other exposures associated with acute myeloid leukemia in a case-referent study. Arch Environ Health 41:77–84PubMedCrossRefGoogle Scholar
  49. 49.
    Gajewski AK, Krzyzanowski M, Majle T (1989) Occupational exposures and leukemia. Rocz Panstw Zakl Hig 40:1–5PubMedGoogle Scholar
  50. 50.
    Järvisalo J, Tola S, Korkala M-L, Järvinen E (1984) A cancer register-based case study of occupations of patients with acute myeloid leukemia. Cancer 54:785–790PubMedCrossRefGoogle Scholar
  51. 51.
    Mele A, Szklo M, Visani G, Stazi MA, Castelli G, Pasquini P, Mandelli F (1994) Hair dye use and other risk-factors for leukemia and pre-leukemia: a case–control study. Am J Epidemiol 139:609–619PubMedGoogle Scholar
  52. 52.
    Reif J, Pearce N, Fraser J (1989) Cancer risks in New Zealand farmers. Int J Epidemiol 18:768–774PubMedCrossRefGoogle Scholar
  53. 53.
    Richardson S, Zittoun R, Bastuji GS, Lasserre V, Guihenneuc C, Cadiou M, Viguie F, Laffont FI (1992) Occupational risk factors for acute leukaemia: a case–control study. Int J Epidemiol 21:1063–1073PubMedCrossRefGoogle Scholar
  54. 54.
    Speer SA, Semenza JC, Kurosaki T, Anton-Culver H (2002) Risk factors for acute myeloid leukemia and multiple myeloma: a combination of GIS and case–control studies. J Environ Health 64:9–16PubMedGoogle Scholar
  55. 55.
    Terry PD, Shore DL, Rauscher GH, Sandler DP (2005) Occupation, hobbies, and acute leukemia in adults. Leuk Res 29:1117–1130PubMedCrossRefGoogle Scholar
  56. 56.
    Sterne JA, Egger M, Smith GD (2001) Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ 323:101–105PubMedCrossRefGoogle Scholar
  57. 57.
    Alder N, Fenty J, Warren F, Sutton AJ, Rushton L, Jones DR, Abrams KR (2006) Meta-analysis of mortality and cancer incidence among workers in the synthetic rubber-producing industry. Am J Epidemiol 164:405–420PubMedCrossRefGoogle Scholar
  58. 58.
    Burns C (2005) Cancer among pesticide manufacturers and applicators. Scand J Work Environ Health 31(suppl 1):9–17PubMedGoogle Scholar
  59. 59.
    Hoppin JA (2005) Integrating exposure measurements into epidemiologic studies in agriculture. Scand J Work Environ Health 31(suppl 1):110–114Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Geneviève Van Maele-Fabry
    • 1
  • Sophie Duhayon
    • 1
  • Dominique Lison
    • 1
  1. 1.Unité de Toxicologie Industrielle et Médecine du travailUniversité Catholique de LouvainBrusselsBelgium

Personalised recommendations