Cerebrovascular Diseases in Workers at Mayak PA: The Difference in Radiation Risk between Incidence and Mortality

<div><p>A detailed analysis of cerebrovascular diseases (CeVD) for the cohort of workers at Mayak Production Association (PA) is presented. This cohort is especially suitable for the analysis of radiation induced circulatory diseases, due to the detailed medical surveillance and information on several risk factors. The risk after external, typically protracted, gamma exposure is analysed, accounting for potential additional internal alpha exposure. Three different endpoints have been investigated: incidence and mortality from all cerebrovascular diseases and incidence of stroke. Particular emphasis was given to the form of the dose-response relationship and the time dependence of the radiation induced risk. Young attained age was observed to be an important, aggravating modifier of radiation risk for incidence of CeVD and stroke. For incidence of CeVD, our analysis supports a dose response sub-linear for low doses. Finally, the excess relative risk per dose was confirmed to be significantly higher for incidence of CeVD compared to CeVD mortality and incidence of stroke. Arguments are presented for this difference to be based on a true biological effect.</p></div

Values of the excess relative risk and 95% confidence intervals for CeVD incidence calculated with multi-model inference.

<p>Values of the excess relative risk and 95% confidence intervals for CeVD incidence calculated with multi-model inference.</p

Crude CeVD incidence rates and 95% confidence intervals of the full cohort.

<p>(A) Crude rates for different calendar years. (B) Crude rates for different ages. The crude rate is the number of cases per person years.</p

Excess relative risk per dose of external gamma radiation and 95% confidence intervals for incidence, separately for different lag-time periods.

<p>Risk has been assigned to the lag-time as in the BEIR VI report <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096309#pone.0096309-Committee1" target="_blank">[35]</a>. The is bound from below by the requirement of a positive hazard for the workers with highest doses.</p

Excess relative risk by categories of cumulative external doses.

<p>Excess relative risk and 95% confidence intervals. In the restricted incidence analyses, time since median exposure has been restricted to more than 30 years for males and more than 35 years for females. Results for female mortality have large uncertainties and are not shown.</p

Number of persons, person years and cases for the different analyses performed in this work.

<p>For CeVD incidence, the cohort was restricted with respect to certain ages and calendar years and the main analysis refers only to reactor workers.</p><p>Number of persons, person years and cases for the different analyses performed in this work.</p

Excess relative risk per dose for external gamma radiation for various lag-times.

<p>Excess relative risk per dose () with 95% confidence levels. The LNT model was applied using various lag-times. Deviances () are compared to the analysis with a lag-time of ten years.</p

Illustrations of the variables and functions used for dose modification.

<p>(A) Definition of the time variables. (B) The step function in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096309#pone.0096309.e018" target="_blank">eq. (2)</a>.</p

Number of persons, person years and cases for the different analyses performed in this work, separately for males and females.

<p>Number of persons, person years and cases for the different analyses performed in this work, separately for males and females.</p

Excess relative risk for CeVD incidence at an attained age of 60 years.

<p>Thin lines correspond to the final, non nested models, numbered according to Fig. A1 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125904#pone.0125904.s001" target="_blank">S1 Appendix</a>: 1) LNT model with step in age attained, Akaike weight 23%; 1’) LNT model exponential in age attained, Akaike weight 12%; 2) Quadratic model with step in age attained, Akaike weight 53%; 9) Sigmoid model with step in age attained, Akaike weight 11%. The thick line with 95% confidence band represents the result of multi-model inference.</p