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Exposure and genetics increase risk of beryllium sensitisation and chronic beryllium disease in the nuclear weapons industry
  1. Michael V Van Dyke1,2,
  2. John W Martyny1,2,3,
  3. Margaret M Mroz1,
  4. Lori J Silveira1,
  5. Matt Strand1,
  6. Donna L Cragle4,
  7. William G Tankersley4,
  8. Susan M Wells4,
  9. Lee S Newman3,
  10. Lisa A Maier1,3
  1. 1Hollis Laboratory, Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, Colorado, USA
  2. 2Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado, USA
  3. 3University of Colorado Denver School of Medicine and Colorado School of Public Health, Denver, Colorado, USA
  4. 4Oak Ridge Associated Universities, Oak Ridge, Tennessee, USA
  1. Correspondence to Dr Michael V Van Dyke, Division of Environmental and Occupational Health Sciences, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA; vandykem{at}


Objectives Beryllium sensitisation (BeS) and chronic beryllium disease (CBD) are caused by exposure to beryllium with susceptibility affected by at least one well-studied genetic host factor, a glutamic acid residue at position 69 (E69) of the HLA-DPβ chain (DPβE69). However, the nature of the relationship between exposure and carriage of the DPβE69 genotype has not been well studied. The goal of this study was to determine the relationship between DPβE69 and exposure in BeS and CBD.

Methods Current and former workers (n=181) from a US nuclear weapons production facility, the Y-12 National Security Complex (Oak Ridge, Tennessee, USA), were enrolled in a case–control study including 35 individuals with BeS and 19 with CBD. HLA-DPB1 genotypes were determined by PCR-SSP. Beryllium exposures were assessed through worker interviews and industrial hygiene assessment of work tasks.

Results After removing the confounding effect of potential beryllium exposure at another facility, multivariate models showed a sixfold (OR 6.06, 95% CI 1.96 to 18.7) increased odds for BeS and CBD combined among DPβE69 carriers and a fourfold (OR 3.98, 95% CI 1.43 to 11.0) increased odds for those exposed over an assigned lifetime-weighted average exposure of 0.1 μg/m3. Those with both risk factors had higher increased odds (OR 24.1, 95% CI 4.77 to 122).

Conclusion DPβE69 carriage and high exposure to beryllium appear to contribute individually to the development of BeS and CBD. Among workers at a beryllium-using facility, the magnitude of risk associated with either elevated beryllium exposure or carriage of DPβE69 alone appears to be similar.

  • Beryllium
  • genetics
  • chronic beryllium disease
  • beryllium sensitisation
  • nuclear workers
  • gene-environment
  • occupational exposure
  • epidemiology
  • respiratory
  • retrospective exposure assessment
  • metals

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  • This work is from a dissertation submitted to the Academic Faculty of Colorado State University in partial fulfilment of the requirements for the degree of Doctor of Philosophy.

  • Funding This study was supported by grant P01 ES011810 from NIEHS/NIH and 1 UL1 RR025780 from NCRR/NIH.

  • Competing interests MVV, JWM, MMM, LJS, MS and LAM are employed by National Jewish Health, a non-profit medical institution that offers the beryllium lymphocyte proliferation test on a commercial basis and provides medical surveillance and consultation to beryllium industries. DLC, WGT and SMW are employed by Oak Ridge Associated Universities which provide medical surveillance including the beryllium lymphocyte proliferation test to facilities using beryllium containing materials. LSN is the CEO of Axion Health, a company also providing medical surveillance services to beryllium using facilities.

  • Ethics approval This study was conducted with the approval of the National Jewish Health IRB and US Department of Energy Central IRB.

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

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