Cancer Causes & Control

, Volume 24, Issue 1, pp 1–12 | Cite as

Lung cancer risk at low cumulative asbestos exposure: meta-regression of the exposure–response relationship

  • Sjoukje van der BijEmail author
  • Hendrik Koffijberg
  • Virissa Lenters
  • Lützen Portengen
  • Karel G. M. Moons
  • Dick Heederik
  • Roel C. H. Vermeulen
Review article



Existing estimated lung cancer risks per unit of asbestos exposure are mainly based on, and applicable to, high exposure levels. To assess the risk at low cumulative asbestos exposure, we provide new evidence by fitting flexible meta-regression models, a notably new and more robust method.


Studies were selected if lung cancer risk per cumulative asbestos exposure in at least two exposure categories was reported. From these studies (n = 19), we extracted 104 risk estimates over a cumulative exposure range of 0.11–4,710 f-y/ml. We fitted linear and natural spline meta-regression models to these risk estimates. A natural spline allows risks to vary nonlinearly with exposure, such that estimates at low exposure are less affected by estimates in the upper exposure categories. Associated relative risks (RRs) were calculated for several low cumulative asbestos exposures.


A natural spline model fitted our data best. With this model, the relative lung cancer risk for cumulative exposure levels of 4 and 40 f-y/ml was estimated between 1.013 and 1.027, and 1.13 and 1.30, respectively. After stratification by fiber type, a non-significant three- to fourfold difference in RRs between chrysotile and amphibole fibers was found for exposures below 40 f-y/ml. Fiber-type-specific risk estimates were strongly influenced by a few studies.


The natural spline regression model indicates that at lower asbestos exposure levels, the increase in RR of lung cancer due to asbestos exposure may be larger than expected from previous meta-analyses. Observed potency differences between different fiber types are lower than the generally held consensus. Low-exposed industrial or population-based cohorts with quantitative estimates of asbestos exposure a required to substantiate the risk estimates at low exposure levels from our new, flexible meta-regression.


Amphiboles Asbestos Chrysotile Exposure Lung cancer Meta-analysis 



This study was supported by the Institute for Asbestos Victims, The Netherlands.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10552_2012_107_MOESM1_ESM.doc (123 kb)
Supplementary material 1 (DOC 123 kb)


  1. 1.
    Straif K, Brahim-Tallaa L, Baan R, Grosse Y, Secretan B, El GF, Bouvard V, Guha N et al (2009) A review of human carcinogens–part C: metals, arsenic, dusts, and fibres. Lancet Oncol 10:453–454PubMedCrossRefGoogle Scholar
  2. 2.
    Berman DW, Crump KS (2008) A meta-analysis of asbestos-related cancer risk that addresses fiber size and mineral type. Crit Rev Toxicol 38(Suppl 1):49–73PubMedCrossRefGoogle Scholar
  3. 3.
    Hodgson JT, Darnton A (2000) The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure. Ann Occup Hyg 44:565–601PubMedGoogle Scholar
  4. 4.
    Lenters V, Vermeulen R, Dogger S, Stayner L, Portengen L, Burdorf A, Heederik D (2011) A meta-analysis of asbestos and lung cancer: Is better quality exposure assessment associated with steeper slopes of the exposure-response relationships? Environ Health Perspect 119:1547–1555Google Scholar
  5. 5.
    Lash TL, Crouch EA, Green LC (1997) A meta-analysis of the relation between cumulative exposure to asbestos and relative risk of lung cancer. Occup Environ Med 54:254–263PubMedCrossRefGoogle Scholar
  6. 6.
    Virta RL (2005) Mineral commodity profiles-asbestos: U.S. Geological Survey Circular 1255-KK. p 56Google Scholar
  7. 7.
    Gustavsson P, Nyberg F, Pershagen G, Scheele P, Jakobsson R, Plato N (2002) Low-dose exposure to asbestos and lung cancer: dose-response relations and interaction with smoking in a population-based case-referent study in Stockholm, Sweden. Am J Epidemiol 155:1016–1022PubMedCrossRefGoogle Scholar
  8. 8.
    Vlaanderen J, Portengen L, Rothman N, Lan Q, Kromhout H, Vermeulen R (2010) Flexible meta-regression to assess the shape of the benzene-leukemia exposure-response curve. Environ Health Perspect 118:526–532PubMedCrossRefGoogle Scholar
  9. 9.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  10. 10.
    Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135:1301–1309PubMedGoogle Scholar
  11. 11.
    Harrel FE (2001) Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis. Springer, New YorkGoogle Scholar
  12. 12.
    Berman DW, Crump KS (2008) Update of potency factors for asbestos-related lung cancer and mesothelioma. Crit Rev Toxicol 38(Suppl 1):1–47PubMedCrossRefGoogle Scholar
  13. 13.
    Armstrong BG (1998) Effect of measurement error on epidemiological studies of environmental and occupational exposures. Occup Environ Med 55:651–656PubMedCrossRefGoogle Scholar
  14. 14.
    Shi JQ, Copas JB (2004) Meta-analysis for trend estimation. Stat Med 23:3–19PubMedCrossRefGoogle Scholar
  15. 15.
    National Institute for Occupational Safety and Health (1976) Revised Recommended Asbestos Standard. National Institute for Occupational Safety and Health, Washington, DC (DHHS (NIOSH) Publication No. 77–169)Google Scholar
  16. 16.
    Occupational Safety and Health Administration Health (1995) Asbestos standard for general industry. Occupational Safety and Health Administration, Washington, DC (OSHA publication 3095 1995 (revised))Google Scholar
  17. 17.
    Rothpearl A (1989) The jackknife technique in statistical analysis. Chest 95:940PubMedCrossRefGoogle Scholar
  18. 18.
    Stayner L, Steenland K, Dosemeci M, Hertz-Picciotto I (2003) Attenuation of exposure-response curves in occupational cohort studies at high exposure levels. Scand J Work Environ Health 29:317–324PubMedCrossRefGoogle Scholar
  19. 19.
    van Loon AJ, Kant IJ, Swaen GM, Goldbohm RA, Kremer AM, van den Brandt PA (1997) Occupational exposure to carcinogens and risk of lung cancer: results from The Netherlands cohort study. Occup Environ Med 54:817–824PubMedCrossRefGoogle Scholar
  20. 20.
    De Matteis S, Consonni D, Lubin JH, Tucker M, Peters S, Vermeulen RC, Kromhout H, Bertazzi PA et al (2012) Impact of occupational carcinogens on lung cancer risk in a general population. Int J Epidemiol 41:711–721PubMedCrossRefGoogle Scholar
  21. 21.
    Frost G, Harding AH, Darnton A, McElvenny D, Morgan D (2008) Occupational exposure to asbestos and mortality among asbestos removal workers: a Poisson regression analysis. Br J Cancer 99:822–829PubMedCrossRefGoogle Scholar
  22. 22.
    Stayner LT, Dankovic DA, Lemen RA (1996) Occupational exposure to chrysotile asbestos and cancer risk: a review of the amphibole hypothesis. Am J Public Health 86:179–186PubMedCrossRefGoogle Scholar
  23. 23.
    Loomis D, Dement J, Richardson D, Wolf S (2010) Asbestos fibre dimensions and lung cancer mortality among workers exposed to chrysotile. Occup Environ Med 67:580–584PubMedCrossRefGoogle Scholar
  24. 24.
    Stayner L, Kuempel E, Gilbert S, Hein M, Dement J (2008) An epidemiological study of the role of chrysotile asbestos fibre dimensions in determining respiratory disease risk in exposed workers. Occup Environ Med 65:613–619PubMedCrossRefGoogle Scholar
  25. 25.
    Berman DW (2010) Comparing milled fiber, Quebec ore, and textile factory dust: has another piece of the asbestos puzzle fallen into place? Crit Rev Toxicol 40:151–188PubMedCrossRefGoogle Scholar
  26. 26.
    Dement JM, Kuempel ED, Zumwalde RD, Smith RJ, Stayner LT, Loomis D (2008) Development of a fibre size-specific job-exposure matrix for airborne asbestos fibres. Occup Environ Med 65:605–612PubMedCrossRefGoogle Scholar
  27. 27.
    Liddell FD, McDonald AD, McDonald JC (1997) The 1891–1920 birth cohort of Quebec chrysotile miners and millers: development from 1904 and mortality to 1992. Ann Occup Hyg 41:13–36PubMedGoogle Scholar
  28. 28.
    Pira E, Pelucchi C, Piolatto PG, Negri E, Bilei T, La VC (2009) Mortality from cancer and other causes in the Balangero cohort of chrysotile asbestos miners. Occup Environ Med 66:805–809PubMedCrossRefGoogle Scholar
  29. 29.
    McDonald AD, Fry JS, Woolley AJ, McDonald JC (1984) Dust exposure and mortality in an American chrysotile asbestos friction products plant. Br J Ind Med 41:151–157PubMedGoogle Scholar
  30. 30.
    Hein MJ, Stayner LT, Lehman E, Dement JM (2007) Follow-up study of chrysotile textile workers: cohort mortality and exposure-response. Occup Environ Med 64:616–625PubMedCrossRefGoogle Scholar
  31. 31.
    Loomis D, Dement JM, Wolf SH, Richardson DB (2009) Lung cancer mortality and fibre exposures among North Carolina asbestos textile workers. Occup Environ Med 66:535–542PubMedCrossRefGoogle Scholar
  32. 32.
    Berry G, de Klerk NH, Reid A, Ambrosini GL, Fritschi L, Olsen NJ, Merler E, Musk AW (2004) Malignant pleural and peritoneal mesotheliomas in former miners and millers of crocidolite at Wittenoom. Western Australia. Occup Environ Med 61:e14Google Scholar
  33. 33.
    Seidman H, Selikoff IJ, Gelb SK (1986) Mortality experience of amosite asbestos factory workers: dose-response relationships 5 to 40 years after onset of short-term work exposure. Am J Ind Med 10:479–514PubMedGoogle Scholar
  34. 34.
    Levin JL, McLarty JW, Hurst GA, Smith AN, Frank AL (1998) Tyler asbestos workers: mortality experience in a cohort exposed to amosite. Occup Environ Med 55:155–160PubMedCrossRefGoogle Scholar
  35. 35.
    Sullivan PA (2007) Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study. Environ Health Perspect 115:579–585PubMedCrossRefGoogle Scholar
  36. 36.
    Berry G, Newhouse ML (1983) Mortality of workers manufacturing friction materials using asbestos. Br J Ind Med 40:1–7PubMedGoogle Scholar
  37. 37.
    Finkelstein MM (1984) Mortality among employees of an Ontario asbestos-cement factory. Am Rev Respir Dis 129:754–761PubMedGoogle Scholar
  38. 38.
    Hughes JM, Weill H, Hammad YY (1987) Mortality of workers employed in two asbestos cement manufacturing plants. Br J Ind Med 44:161–174PubMedGoogle Scholar
  39. 39.
    Albin M, Jakobsson K, Attewell R, Johansson L, Welinder H (1990) Mortality and cancer morbidity in cohorts of asbestos cement workers and referents. Br J Ind Med 47:602–610PubMedGoogle Scholar
  40. 40.
    Lacquet LM, van der Linden L, Lepoutre J (1980) Roentgenographic lung changes, asbestosis and mortality in a Belgian asbestos-cement factory. IARC Sci Publ, pp 783–793Google Scholar
  41. 41.
    Enterline PE, Hartley J, Henderson V (1987) Asbestos and cancer: a cohort followed up to death. Br J Ind Med 44:396–401PubMedGoogle Scholar
  42. 42.
    Selikoff IJ, Seidman H (1991) Asbestos-associated deaths among insulation workers in the United States and Canada, 1967–1987. Ann N Y Acad Sci 643:1–14PubMedCrossRefGoogle Scholar
  43. 43.
    McDonald AD, Fry JS, Woolley AJ, McDonald JC (1983) Dust exposure and mortality in an American factory using chrysotile, amosite, and crocidolite in mainly textile manufacture. Br J Ind Med 40:368–374PubMedGoogle Scholar
  44. 44.
    Peto J, Doll R, Hermon C, Binns W, Clayton R, Goffe T (1985) Relationship of mortality to measures of environmental asbestos pollution in an asbestos textile factory. Ann Occup Hyg 29:305–355PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Sjoukje van der Bij
    • 1
    • 3
    Email author
  • Hendrik Koffijberg
    • 1
  • Virissa Lenters
    • 2
  • Lützen Portengen
    • 2
  • Karel G. M. Moons
    • 1
  • Dick Heederik
    • 1
    • 2
  • Roel C. H. Vermeulen
    • 1
    • 2
  1. 1.Julius Center for Health Sciences and Primary CareUniversity Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Division of Environmental Epidemiology, Institute for Risk Assessment SciencesUtrecht UniversityUtrechtThe Netherlands
  3. 3.Julius Center for Health Sciences and Primary CareUniversity Medical Center UtrechtUtrechtThe Netherlands

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