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Pooled study of occupational exposure to aromatic hydrocarbon solvents and risk of multiple myeloma
  1. Anneclaire J De Roos1,
  2. John Spinelli2,3,
  3. Elizabeth B Brown4,
  4. Djordje Atanackovic5,
  5. Dalsu Baris6,
  6. Leslie Bernstein7,
  7. Parveen Bhatti8,9,
  8. Nicola J Camp5,
  9. Brian C Chiu10,
  10. Jacqueline Clavel11,12,
  11. Wendy Cozen13,
  12. Silvia De Sanjosé14,
  13. James A Dosman15,
  14. Jonathan N Hofmann6,
  15. John R McLaughlin16,
  16. Lucia Miligi17,
  17. Alain Monnereau11,12,18,
  18. Laurent Orsi11,12,
  19. Mark P Purdue6,
  20. Leah H Schinasi1,
  21. Guido J Tricot19,
  22. Sophia S Wang7,
  23. Yawei Zhang20,21,
  24. Brenda M Birmann22,
  25. Pierluigi Cocco23
  1. 1 Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania, USA
  2. 2 Population Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada
  3. 3 School of Population and Public Health, UBC, Vancouver, Canada
  4. 4 Department of Pathology, University of Alabama, Birmingham, Alabama, USA
  5. 5 Division of Hematology and Hematological Malignancies, University of Utah School of Medicine, Salt Lake City, Utah, USA
  6. 6 Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
  7. 7 Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, California, USA
  8. 8 Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
  9. 9 Cancer Control Research, BC Cancer Agency, Vancouver, British Columbia, Canada
  10. 10 Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA
  11. 11 INSERM U1153, Epidemiology and Biostatistics Sorbonne Paris Cité (CRESS), Paris, France
  12. 12 Epidemiology of Childhood and Adolescent Cancers Team (EPICEA), Paris-Descartes University, Villejuif, France
  13. 13 Departments of Preventive Medicine and Pathology, USC Keck School of Medicine, University of Southern California, Los Angeles, California, USA
  14. 14 Cancer Epidemiology Research Programme, Catalan Institute of Oncology, Barcelona, Spain
  15. 15 Canadian Centre for Health and Safety in Agriculture, University of Saskatchewan, Saskatoon, Canada
  16. 16 Public Health Ontario, Toronto, Ontario, Canada
  17. 17 Unit of Environmental and Occupational Epidemiology, Oncological Network, Prevention, Research Institute, Florence, Italy
  18. 18 Inserm Team EPICENE U1219, Hematological Malignancies Registry of Gironde, Bergonie Institute, Bordeaux, France
  19. 19 Internal Medicine, University of Iowa, Iowa City, USA
  20. 20 School of Public Health, Yale University, New Haven, Connecticut, USA
  21. 21 School of Medicine, Yale University, New Haven, Connecticut, USA
  22. 22 Channing Division of Network Medicine, Division of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
  23. 23 Department of Public Health and Clinical Molecular Medicine, University of Cagliari, Cagliari, Italy
  1. Correspondence to Dr Anneclaire J De Roos, Drexel University Dornsife School of Public Health, Philadelphia, PA 19104, USA; aderoos{at}


Objectives To investigate the association between occupational exposure to aromatic hydrocarbon solvents and risk of multiple myeloma (MM) in a large, consortium-based study.

Methods We pooled data on 2854 cases and 10 743 controls from nine studies participating in the InterLymph consortium. Occupational exposures to benzene, toluene and xylene were assigned by a job–exposure matrix, coupled with ‘correction’ of exposure probability by self-reported or expert-assessed exposure from the individual studies. Cumulative intensity was calculated as the job-specific exposure intensity multiplied by job duration, summed across jobs. Associations were estimated using logistic regression, with inclusion of covariates for study matching factors and other potential confounders. We repeated our main analysis using random-effects meta-analysis to evaluate heterogeneity of effect.

Results Benzene, toluene and xylene were each associated with MM. For the three solvents, the highest quartile of high-probability cumulative intensity exposure (vs unexposed) was associated with 42% to 63% increased risks of MM. Associations with toluene and xylene exposures were fairly consistent and robust to sensitivity analyses. The estimated effect for benzene was moderately heterogeneous between the studies. Each solvent’s association with MM was stronger for exposure occurring within 20 years of diagnosis than with exposure lagged by more than 20 years.

Conclusions Our study adds important evidence for a role of aromatic hydrocarbon solvents in causation of MM. The difficulty in disentangling individual compounds in this group and a lack of data on potential carcinogenicity of toluene and xylene, in widespread current use, underscore a need for further epidemiological evaluation.

  • epidemiology
  • public health
  • cancer
  • retrospective exposure assessment

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  • Contributors AJDR, PC, JS, EBB and BMB conceived of and designed the study. AJDR, PC and LHS carried out the study protocol through data acquisition, data organisation and data analysis. All authors contributed to data interpretation, drafting the manuscript and revising the work for important intellectual content.

  • Funding This study was funded by the National Institute of Environmental Health Sciences (5R21ES021592).

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval Drexel University IRB.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data from this pooled study that comprised multiple case–control studies conducted by individual institutions may be shared only with permission of the individual institutions, which hold the original study data.