@entity0 risk and possible mechanisms of radiation-induced genomic instability in the Swedish XXXX cohort after reanalyzed dosimetry.

@entity1 @entity0 @entity2695 @entity272 @entity105
The cohort of 17,200 female Swedish @entity2695 @entity1 , who had been exposed to ionizing radiation because of @entity272 , was analyzed for @entity0 incidence with descriptive excess relative risk models and mechanistic models of @entity105 . The dosimetry system has recently been updated, leading to substantially reduced doses for the most highly exposed part of the Stockholm cohort. The follow-up includes @entity1 until December 2009 with 877 @entity0 cases. All models agree on the risk estimates. The excess relative and excess absolute risk at the age of 50 years are 0.48 Gy(-1) (95% CI 0.28; 0.69) and 10.4 (10(4)PYR Gy)(-1) (95% CI 6.1; 14.4) (95% CI 6.1; 14.4), respectively. These risk estimates are about a factor of 2 higher than previous analyses of this cohort as a consequence of the re-evaluation of the dosimetry system. Explicit models incorporating effects of genomic instability were developed and applied to the @entity2695 cohort. It was found that a radiation-induced transition towards genomic instability was highly significant. The models indicate that the main effect of radiation-induced genomic instability is to increase the rate of transition of non-initiated cells to initiated cells with a proliferative advantage. The magnitude of such an acceleration cannot be inferred from epidemiological data alone, but must be complemented by radiobiological measurements.
