Exposure-lag-response associations between lung cancer mortality and radon exposure in German uranium miners

Radiat Environ Biophys. 2019 Aug;58(3):321-336. doi: 10.1007/s00411-019-00800-6. Epub 2019 Jun 19.

Abstract

Exposure-lag-response associations shed light on the duration of pathogenesis for radiation-induced diseases. To investigate such relations for lung cancer mortality in the German uranium miners of the Wismut company, we apply distributed lag non-linear models (DLNMs) which offer a flexible description of the lagged risk response to protracted radon exposure. Exposure-lag functions are implemented with B-Splines in Cox models of proportional hazards. The DLNM approach yielded good agreement of exposure-lag-response surfaces for the German cohort and for the previously studied cohort of American Colorado miners. For both cohorts, a minimum lag of about 2 year for the onset of risk after first exposure explained the data well, but possibly with large uncertainty. Risk estimates from DLNMs were directly compared with estimates from both standard radio-epidemiological models and biologically based mechanistic models. For age > 45 year, all models predict decreasing estimates of the Excess Relative Risk (ERR). However, at younger age, marked differences appear as DLNMs exhibit ERR peaks, which are not detected by the other models. After comparing exposure-responses for biological processes in mechanistic risk models with exposure-responses for hazard ratios in DLNMs, we propose a typical period of 15 year for radon-related lung carcinogenesis. The period covers the onset of radiation-induced inflammation of lung tissue until cancer death. The DLNM framework provides a view on age-risk patterns supplemental to the standard radio-epidemiological approach and to biologically based modeling.

Keywords: Distributed lag non-linear models; Exposure–lag–response surface; Lung cancer mortality; Radon exposure; Uranium miners.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Air Pollutants, Occupational / analysis*
  • Air Pollutants, Radioactive / analysis*
  • Carcinogenesis
  • Cohort Studies
  • Germany / epidemiology
  • Humans
  • Lung Neoplasms / mortality*
  • Male
  • Middle Aged
  • Occupational Exposure / statistics & numerical data*
  • Radon*
  • Risk
  • Time Factors
  • Uranium

Substances

  • Air Pollutants, Occupational
  • Air Pollutants, Radioactive
  • Uranium
  • Radon