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.

Keywords:

• Circulatory disease
• radiation
• heart disease
• stroke
• cataract
• central nervous system
• in utero
• childhood
• glaucoma
• macular degeneration
• review

Acknowledgements

The authors are grateful for the detailed and helpful comments of the two referees and the Associate Editor.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Notes

1 In all that follows we shall denote doses >5 Gy as very high, doses of 1-5 Gy as high, doses of 0.5-1 Gy as moderate, doses of 0.1-0.5 Gy as low-moderate and doses <0.1 Gy as low, somewhat consistent with other definitions that have been used (ICRP 2007; Little et al. 2008; Little, Azizova, et al. 2012; UNSCEAR 2018). We shall denote low dose rate as <5 mGy/hour, again approximately consistent with general usage (Muirhead et al. 1993; Wakeford and Tawn 2010; UNSCEAR 2018).

Additional information

Funding

This work was supported by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics.

Notes on contributors

Mark P. Little

Mark P. Little, D.Phil, joined the National Cancer Institute, Radiation Epidemiology Branch (REB) in 2010, and was promoted to a Senior Investigator in 2012. Previously (2000–2010), he worked in Imperial College London, and before that (1992–2000) at UK National Radiological Protection Board (now part of Public Health England). He is a member of Council of NCRP, and has served as consultant to UNSCEAR, to IAEA, to ICRP, to the UK COMARE, and to NCRP committees SC 1-21 and 1-26. He has particular statistical interests in machine learning algorithms and dose measurement error models. He has over 280 publications in the peer-reviewed literature.

Tamara V. Azizova

Tamara V. Azizova, MD, PhD, is the head and the leading researcher of the clinical department, science deputy director at the Southern Urals Biophysics Institute of the Federal Medical Biological Agency, and the head of the Occupational Radiation Pathology Medical Center of Ozyorsk, Chelyabinsk region, Russia. She serves on ICRP Committee 1, Task Groups 91 and 102, and is an Alternative Representative of a Russian delegation to UNSCEAR. She has published >200 papers in peer reviewed international journals.

Nobuyuki Hamada

Nobuyuki Hamada, RT, PhD, is Senior Research Scientist at CRIEPI Radiation Safety Research Center and Visiting Professor at Hiroshima University Research Institute for Radiation Biology and Medicine. He serves on ICRP Task Groups 102 and 111, NCRP PAC 1, IRPA Phase 3 Task Group on the implementation of the eye lens dose limits, and Consultation Committee on AOP development for space flight health outcomes (Canadian project). He has published >125 papers in peer reviewed international journals.