Low- and moderate-dose non-cancer effects of ionizing radiation in directly exposed individuals, especially circulatory and ocular diseases: a review of the epidemiology

Abstract

Purpose: There are well-known correlations between high and moderate doses (>0.5 Gy) of ionizing radiation exposure and circulatory system damage, also between radiation and posterior subcapsular cataract. At lower dose correlations with circulatory disease are emerging in the Japanese atomic bomb survivors and in some occupationally exposed groups, and are still to some extent controversial. Heterogeneity in excess relative risks per unit dose in epidemiological studies at low (<0.1 Gy) and at low-moderate (>0.1 Gy, <0.5 Gy) doses may result from confounding and other types of bias, and effect modification by established risk factors. There is also accumulating evidence of excess cataract risks at lower dose and low dose rate in various cohorts. Other ocular endpoints, specifically glaucoma and macular degeneration have been little studied. In this paper, we review recent epidemiological findings, and also discuss some of the underlying radiobiology of these conditions. We briefly review some other types of mainly neurological nonmalignant disease in relation to radiation exposure. Conclusions: We document statistically significant excess risk of the major types of circulatory disease, specifically ischemic heart disease and stroke, in moderate-or low-dose exposed groups, with some not altogether consistent evidence suggesting dose-response non-linearity, particularly for stroke. However, the patterns of risk reported are not straightforward. We also document evidence of excess risks at lower doses/dose-rates of posterior subcapsular and cortical cataract in the Chernobyl liquidators, US Radiologic Technologists and Russian Mayak nuclear workers, with fundamentally linear dose-response. Nuclear cataracts are less radiogenic. For other ocular endpoints, specifically glaucoma and macular degeneration there is very little evidence of effects at low doses; radiation-associated glaucoma has been documented only for doses >5 Gy, and so has the characteristics of a tissue reaction. There is some evidence of neurological detriment following low-moderate dose ($0.1-0.2 Gy) radiation exposure in utero or in early childhood.

Areas of research to support the system of radiological protection

“…Some non-cancer effects might be better classified as stochastic effects. Evidence for increased risk of diseases of the circulatory system following exposure to ionising radiation at low to moderate doses and dose-rates has accumulated from epidemiological studies over the recent decade (Azizova et al 2015 ; Tapio et al 2021 ; Little et al 2021 ). These results show an increase in the probability of occurrence with dose, with no variation in severity.…”

Epidemiological Research with Special Reference to Nuclear Worker Studies: Commentary

“…The monitoring of populations exposed to low-dose radiation is important but conclusions should be made with caution considering known and unknown bias. For example, "the very high rates of circulatory disease" [66] in some nuclear worker cohorts from the former Soviet Union are probably caused by habitual overdiagnosis of cardiovascular diseases in unclear cases, which is a known confounder [67]. Reliable evidence in regard to biological effects of low radiation doses can be obtained in extensive animal experiments rather than in epidemiological studies.…”

The Incidence Risk for Primary Glaucoma and Its Subtypes following Chronic Exposure to Ionizing Radiation in the Russian Cohort of Mayak Nuclear Workers

“…Since then, it has widely been considered that ionizing radiation induces such secondary glaucoma (neovascular glaucoma in particular) following high-dose fractionated radiotherapy (e.g., >40 Gy delivered in 2-Gy fractions) [7,8]. In contrast, no significantly increased radiation risk was observed for primary glaucoma, POAG or PACG in several exposed cohorts [9][10][11][12][13][14] until recent studies in Japanese atomic bomb survivors suggested a significantly increased risk for NTG following acute radiation exposure at doses much lower than radiotherapeutic doses [9,10]. This introduces the possibility that radiation exposure induces NTG and raises a question whether such induction depends on dose and dose rates.…”