Mortality Analysis of the Life Span Study (LSS) Cohort Taking into Account Multiple Causes of Death Indicated in Death Certificates

Mortality analyses have been performed using underlying causes of death as reported on death certificates; these are uniquely determined for a deceased person according to the World Health Organization coding system. Comorbidities, the disease conditions other than the underlying cause of death from death certificates recording multiple causes of death, have rarely been explored in Life Span Study subjects. The purpose of this study was to clarify associations between atomic bomb radiation exposure and mortality from combinations of the underlying cause of death and comorbidities. The focused follow-up period was 1977-2003, prior to which death certificate accuracy was unreliable. The study cohort was comprised of 10,017 people for whom the category "all circulatory disease" was listed as the underlying cause of death, of which heart disease (rheumatic, hypertensive and ischemic heart disease) and stroke were major subtypes. Comorbidities considered were pneumonia, renal disease, diabetes mellitus, cancer and the major circulatory disease subtypes listed above. Poisson regression models were used for analyses. Excess relative risks (ERRs) for mortality at 1 Gy were significantly increased when cancer was comorbid with all circulatory disease, heart disease, ischemic heart disease or stroke, ranging from 0.61 [95% confidence interval (CI): 0.13, 1.41; N = 177] for all circulatory diseases to 1.60 (CI: 0.07, 4.86; N = 42) for ischemic heart disease. Among the other comorbidities, only diabetes comorbid with heart disease had a significant radiation dose response (ERR at 1 Gy of 0.62, CI: 0.10, 1.46; N = 128). It remains uncertain if the high ERRs with comorbid cancers were anomalous due to the small number of cases or some dissimilarity in statistical methodologies, or if this might suggest some pathogenetic basis for increased fatality. For this reason, further investigation is required.