Jump to comment:

• Re:Occupational exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case-control study
  Pierluigi Cocco
  Published on: 27 December 2010
• Occupational exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case-control study
  Gerhard Triebig
  Published on: 7 September 2010

• Published on: 27 December 2010

  Re:Occupational exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case-control study

  • Pierluigi Cocco, Associate Professor
  • Other Contributors:
    • Andrea t'Mannetje, Nikolaus Becker, Silvia de Sanjos?, Lenka Foretova, Julia Mareckova, Anthony Staines, Marc Maynadi?, Alexandra Nieters, Paul Brennan, and Paolo Boffetta.

  We thank Dr Triebig for his interesting comments on our article “Occupational exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case-control study�.1,2 Epidemiological evidence is growing about the various etiological factors of specific lymphoma subtypes, and perhaps the different mechanisms involved.3 In our paper, we referred to previous reports suggesting an interaction o...

  Show More

  We thank Dr Triebig for his interesting comments on our article “Occupational exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case-control study�.1,2 Epidemiological evidence is growing about the various etiological factors of specific lymphoma subtypes, and perhaps the different mechanisms involved.3 In our paper, we referred to previous reports suggesting an interaction of occupational benzene exposure with familial history of haematological diseases and history of immune system diseases,4 apparently indicating an immune system disruption as a mechanism of lymphomagenesis among benzene-exposed workers. However, while those hypotheses apply to NHL in general, we did find a positive link with CLL and dubious findings for follicular lymphoma, but not with DLBCL. It is worth commenting that immune dysfunction is reportedly more relevant for DLBCL and marginal zone lymphoma than for CLL and follicular lymphoma.3 We also referred to benzene genotoxicity as a plausible mechanism, as several genotoxic effects of benzene, and particularly, long-arm deletion of chromosome 6 and trisomy of chromosomes 2, 4, 6, 11, 12, 14 and 18, also occur among lymphoma patients.5,6 The etiologic role of benzene is well established for non-lymphocytic leukaemia, and the recent IARC re-evaluation of human carcinogens in the Monographs N. 1-99 has raised the attention for future research on other neoplasms of the lymphohaemopoietic tissue.7 A variety of combinations of multifactorial factors might plausibly intervene in the chain of events leading to each individual subtype of lymphohaemopoietic malignancies. Whether this variety of aetiological patterns is reflected by excess risk in specific time windows since exposure onset is a question perhaps too early to answer. Nonetheless, we followed Dr Triebig suggestion and explored risk of B-cell lymphoma and CLL by year of initiating exposure, whether up to 1970, between 1971 and 1980, or from 1981 onwards. As the Epilymph study started at different times in the participating countries from 1996 onwards, the 10-15 years interval indicated by Dr Triebig would fit into the last time window. While no substantial changes in risk of B-cell lymphoma were observed by time window in all exposed and in those classified with the highest confidence of exposure to benzene, risk of CLL was highest among subjects who started exposure in 1971-1980 (all exposed: OR = 2.24, 95% CI 0.98 - 5.12; high confidence: OR = 3.33, 95% CI 1.01- 11.0), it was still elevated among those whose exposure started before 1970 (all exposed: OR = 1.53, 95% CI 1.08 - 2.17; high confidence: OR = 1.52, 95% CI 0.97- 2.39), and it was not elevated among those who started exposure from 1981 onwards(all exposed: OR = 2.20, 95% CI 0.72 - 6.76; high confidence: OR = 1.27, 95% CI 0.16- 10.2). It is worth mentioning that this last group included only a tiny fraction of the exposed, mainly because of the regulatory restrictions introduced in the ‘70s. Also, subjects exposed to benzene from 1981 onwards might have been exposed to lower concentrations and for a shorter period; therefore, if cumulative dose over time were to be the correct indicator, the absence of effects might be accounted for by lower cumulative doses. As it concerns risk associated with toluene and xylene exposure, Table 5 in our paper shows that the excess risk associated with toluene was mostly accounted for by co-occurrent exposure to benzene.2 On the other hand, the elevated risk associated with xylene exposure was generated by extremely small numbers with isolated exposure to xylene. We don’t feel confident to infer about toluene and xylene risk related to their genotoxicity, based on such poor epidemiological evidence. Further time-related modelling of CLL risk as a function of dose of exposure to benzene, and proper stratification of overlapping exposures, would require pooled analyses of studies with high quality exposure data, an opportunity currently provided only by the Interlymph Consortium. References 1. Triebig G. “Occupational exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case-control study�. Occup Environ Med 2010; e-letter (published 7 September 2010) 2. Cocco P, t’Mannetje A, Fadda D, Melis M, Becker N, de Sanjose´ S, Foretova L, Mareckova J, Staines A, Kleefeld S, Maynadie´ M, Nieters A, Brennan P, Boffetta P. exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case-control study. Occup Environ Med 2010;67:341-347. 3. Morton LM, Wang SS, Cozen W, Chatterjee N, Davis S, Severson RK, Colt JS, Vasf MA, Rothman N, Blair A, Bernstein L, Croos AJ, DeRoos AJ, Engels EA, Hein DW, Hill DA, Kelemen LE, Lim U, Lynch CF, Schenk M, Wacholder S, Ward MH, Hoar Zahm S, Chanock SJ, Cerhan JR, Hartge P. Etiologic heterogeneity among non-Hodgkin lymphoma subtypes. Blood 2008;112:5150-60. 4. Vineis P, Miligi L, Seniori Costantini A. Exposure to solvents and risk of non-Hodgkin lymphoma: clues on putative mechanisms. Cancer Epidemiol Biomarkers Prev 2007;16:381-4. 5. Zhang L, Rothman N, Li G, Guo W, Yang W, Hubbard AE, Hayes RB, Yin S, Lu W, Smith MT. Aberrations in chromosomes associated with lymphoma and therapy-related leukemia in benzene-exposed workers. Environ Mol Mutagen 2007;48:467-74. 6. McHale CM, Lan Q, Corso C, Li G, Zhang L, Vermeulen R, Curry JD, Shen M, Turakulov R, Higuchi R, Germer S, Yin S, Rothman N, Smith MT.. Chromosome translocations in workers exposed to benzene. J Natl Cancer Inst Monogr 2008;39:74-7. 7. Baan R, Grosse Y, Straif K, Secretan B, El Ghissassi F, Bouvard V, Benbrahimm-Tallaa L, Guha N, Freeman C, Galichet L. A review of human carcinogens – Part F: Chemical agents and related occupations. Lancet Oncology 2009;10:1143-4. Conflict of Interest: None Declared

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top
• Published on: 7 September 2010

  Occupational exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case-control study

  • Gerhard Triebig, M.D., M.Sc.

  Considering the temporal association between exposure to benzene and the later development of leukaemia it is questionable if this phenomena is also true for NHL.1 From several independent epidemiologic studies with consistent findings it can be concluded, that 10 to 15 years after exposure to benzene has been stopped, the risk of leukaemia is significantly less or even absent.2,3,4

  Assuming that the underlying...

  Show More

  Considering the temporal association between exposure to benzene and the later development of leukaemia it is questionable if this phenomena is also true for NHL.1 From several independent epidemiologic studies with consistent findings it can be concluded, that 10 to 15 years after exposure to benzene has been stopped, the risk of leukaemia is significantly less or even absent.2,3,4

  Assuming that the underlying mechanism for leukaemia and NHL is the same, it would be important to use the large database of the "Epilymph study" to analyze the temporal pattern between exposure and disease.

  The study found increased risks for chronic lymphocytic leukaemia after exposure to toluene and xylene. A benzene exposure was excluded. These statistical associations must be discussed with respect to the genotoxicologic evidence of these aromatic hydro-carbons. Compared to benzene, toluene and xylene have not been proven as human carcinogens. The IARC Working Group concluded in 1999, that there is inadequate evidence in humans for the carcinogenicity of toluene and xylenes.5 Therefore the associations must be interpreted with caution and do not support causality.

  Literature: 1. Triebig G. Implications of latency period between benzene exposure and development of leukemia - a synopis of literature. Chem Biol Interact 2010; 184: 26-29. 2. Hayes RB, Song-Nian Yin, Dosemeci M. Benzene and the dose related incidence of hematologic neoplasm in China. J Natl Cancer Inst 1997; 89: 1065-1071. 3. Finkelstein MM. Leukemia after exposure to benzene: temporal trends and implications for standards. Am J Ind Med 2000; 38: 1-7. 4. Glass DC, Sim MR, Fritschi L, Gray CN, Jolley DJ, Gibbons CG. Letter to the editor. Leukemia risk and relvant benzene exposure period. Am J Ind Med 2002; 42:481-489 5. IARC Monographs on the evaluation of carcinogenic risks to humans. Re- evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide. Volume 71, Part two (Toluene) and Part three (Xylene). World Health Organization International Agency for Research on Cancer, 1999

  Correspondence to: Prof. Dr. G. Triebig, M.D., M.Sc. Institute and Outpatient Clinic for Occupational and Social Medicine University of Heidelberg Vossstr. 2 D-69115 Heidelberg Germany Tel.: ( 49) 6221 56 51 01 Fax: ( 49) 6221 56 29 91 Email: GTriebig@med.uni-heidelberg.de

  Conflict of Interest:

  None declared

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top