Occupational exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case–control study
- P Cocco1,
- A t'Mannetje2,
- D Fadda1,
- M Melis1,
- N Becker3,
- S de Sanjosé4,
- L Foretova5,
- J Mareckova6,
- A Staines7,
- S Kleefeld8,
- M Maynadié9,
- A Nieters3,
- P Brennan10,
- P Boffetta11
- 1Department of Public Health, Occupational Health Section, University of Cagliari, Cagliari, Italy
- 2Centre for Public Health Research, Massey University, Wellington, New Zealand
- 3German Cancer Research Centre, Heidelberg, Germany
- 4Catalan Institute of Oncology, Barcelona, and Centro de Investigació n Biomédica en Red de Epidemiología y Salud Pública (CIBERESP) Spain
- 5Department of Cancer Epidemiology and Genetics, Brno, Czech Republic
- 6Institute of Public Health, Brno, Czech Republic
- 7Dublin City University, Dublin, Ireland
- 8National University of Ireland, Galway, Ireland
- 9Dijon University Hospital, Dijon, France
- 10International Agency for Research on Cancer, Lyon, France
- 11The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY and International Prevention Research Institute, Lyon, France
- Correspondence to Pierluigi Cocco, Department of Public Health, Occupational Health Section, University of Cagliari, Asse Didattico – Policlinico Universitario, SS 554, km 4,500, 09042 Monserrato (Cagliari), Italy;
Contributors All co-authors participated in planning the study design, in conducting the study and data acquisition (PBo, SdS, PBr, PC, LF, MMa, AN, AS), AtM conducted the occupational experts training and prepared the reference materials for the exposure assessment, PC and AtM supervised the occupational exposure assessment which was conducted in collaboration with MMe, JM and SK. PC conducted the epidemiological analysis in collaboration with DF and MMe, and wrote the manuscript. All the co-authors reviewed the manuscript and have seen and approved the final version.
- Accepted 5 October 2009
Background Several studies have suggested an association between occupational exposure to solvents and lymphoma risk. However, findings are inconsistent and the role of specific chemicals is not known.
Objective To investigate the role of occupational exposure to organic solvents in the aetiology of B-cell non-Hodgkin's lymphoma (B-NHL) and its major subtypes, as well as Hodgkin's lymphoma and T-cell lymphoma.
Methods 2348 lymphoma cases and 2462 controls participated in a case–control study in six European countries. A subset of cases were reviewed by a panel of pathologists to ensure diagnostic consistency. Exposure to solvents was assessed by industrial hygienists and occupational experts based on a detailed occupational questionnaire.
Results Risk of follicular lymphoma significantly increased with three independent metrics of exposure to benzene, toluene and xylene (BTX) (combined p=4×10−7) and to styrene (p=1×10−5), and chronic lymphocytic leukaemia (CLL) risk increased with exposure to solvents overall (p=4×10−6), BTX (p=5×10−5), gasoline (p=8×10−5) and other solvents (p=2×10−6). Risk of B-NHL for ever exposure to solvents was not elevated (OR=1.1, 95% CI 1.0 to 1.3), and that for CLL and follicular lymphoma was 1.3 (95% CI 1.1 to 1.6) and 1.3 (95% CI 1.0 to 1.7), respectively. Exposure to benzene accounted, at least partially, for the association observed with CLL risk. Hodgkin's lymphoma and T-cell lymphoma did not show an association with solvent exposure.
Conclusion This analysis of a large European dataset confirms a role of occupational exposure to solvents in the aetiology of B-NHL, and particularly, CLL. It is suggested that benzene is most likely to be implicated, but we cannot exclude the possibility of a role for other solvents in relation to other lymphoma subtypes, such as follicular lymphoma. No association with risk of T-cell lymphoma and Hodgkin's lymphoma was shown.
Funding The study was supported by grants of the European Commission, 5th Framework Program, Quality of Life (grant No QLK4-CT-2000-00422); European Commission, 6th Framework Program, FP6-2003-FOOD-2-B (contract No 023103); the Spanish Ministry of Health (grant No 04-0091, RCESP 09-10); the German Federal Office for Radiation Protection (grants No StSch4261 and StSch4420); La Fondation de France; and Compagnia di San Paolo di Torino, Programma Oncologia 2001.
Competing interests PBo participated as a co-author in a review on styrene presented by the Styrene Information and Research Center (STIRC) as a public comment to the US National Toxicology Program's Board of Scientific Counselors. None of the co-authors declare financial interests or other connections, direct or indirect, related to the work reported or the conclusions, implications, or opinions stated in this paper.
Ethics approval This study was conducted with the approval of the relevant ethics committees at all centres participating in the study.
Provenance and peer review Not commissioned; externally peer reviewed.