The carcinogenic risk induced by low doses of ionizing radiation is controversial. It cannot be assessed with epidemiologic methods alone because at low doses the data are imprecise and often conflicting. Since the 1970s, the radiation protection community has estimated the risk of low doses by means of extrapolation from the risk assessed at high doses, generally by using the linear no-threshold (LNT) model.

The LNT relationship implies proportionality between dose and cancer risk. This approach is based on one set of data and two hypotheses: (a) The relationship between dose and DNA damage in vivo seems linear from 1 mGy to 100 Gy with use of H2AX foci as a marker for DNA double-strand breaks (DSBs)—however, this marker is not specific (1); (b) each DSB is hypothesized to have the same probability of inducing cell transformation, irrespective of the quantity of DSBs present simultaneously in the cell; and (c) each transformed cell is hypothesized to have the same probability of developing into an invasive cancer, irrespective of the dose delivered to the tissue. The advances during the past 2 decades in radiation biology, the understanding of carcinogenesis, and the discovery of defenses against carcinogenesis challenge the LNT model, which appears obsolete (2–6).

Life developed in a bath of ionizing radiation and solar ultraviolet radiation and created aerobic organisms requiring (a) defenses against the metabolically induced reactive oxygen species, (b) DNA repair, and (c) elimination of damaged cells. Several sets of data show the efficacy of these defenses to be much higher at low than at high doses and for fractionated or protracted irradiation than for acute irradiation.

The LNT model was introduced as a concept to facilitate radiation protection (7). But the use of this model led to the claim that even the smallest dose (one electron traversing a cell) may initiate carcinogenesis—for instance, from diagnostic x-ray sources (8,9). This claim is highly hypothetical and has resulted in medical, economic, and other societal harm.

The French Academies report (10) concluded that the LNT model and its use for assessing the risks associated with low doses are not based on scientific evidence. In contrast, the Biological Effects of Ionizing Radiation (BEIR) VII report (11) and that of the International Commission on Radiological Protection (ICRP) (12) recommended the use of the LNT model. We wish to update this debate by using recent radiation biologic and epidemiologic data.

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The linear no-threshold relationship is inconsistent with radiation biologic and experimental data.

Natural radiation is the major source of human exposure to ionising radiation, and its largest contributing component to effective dose arises from inhalation of 222Rn and its radioactive progeny. However, despite extensive knowledge of radiation risks gained through epidemiologic investigations and mechanistic considerations, the health effects of chronic low-level radiation exposure are still poorly understood. The present paper reviews the possible contribution of studies of populations living in high natural background radiation (HNBR) areas (Guarapari, Brazil; Kerala, India; Ramsar, Iran; Yangjiang, China), including radon-prone areas, to low dose risk estimation. Much of the direct information about risk related to HNBR comes from case–control studies of radon and lung cancer, which provide convincing evidence of an association between long-term protracted radiation exposures in the general population and disease incidence. The success of these studies is mainly due to the careful organ dose reconstruction (with relatively high doses to the lung), and to the fact that large-scale collaborative studies have been conducted to maximise the statistical power and to ensure the systematic collection of information on potential confounding factors. In contrast, studies in other (non-radon) HNBR areas have provided little information, relying mainly on ecological designs and very rough effective dose categorisations. Recent steps taken in China and India to establish cohorts for follow-up and to conduct nested case–control studies may provide useful information about risks in the future, provided that careful organ dose reconstruction is possible and information is collected on potential confounding factors.

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Human exposure to high natural background radiation: what can it teach us about radiation risks?

GUEST EDITORIAL PREFACE EXECUTIVE SUMMARY INTRODUCTION EPIDEMIOLOGICAL CONSIDERATION Introduction Inferences based on acute doses in the moderate-to-high dose range Estimation of risk at low doses and low dose rates Thresholds vs. the linear, no-threshold theory Conclusion: Implications for low-dose cancer risk LOW-DOSE RISK BIOLOGY Introduction Damage caused by radiation Damage Response Pathways Fidelity of DSB repair Impact of defects in DNA repair, checkpoint control and apoptosis Conclusions CELLULAR CONSEQUENCES OF RADIATION-INDUCED DAMAGE Radiation- induced Chromosome Aberrations Radiation-Induced Somatic Cell Mutations Adaptive Response, Genomic Instability and Bystander Effect Conclusions: Implications for Risk Assessment CARCINOGENIC EFFECTS OF IONIZING RADIATION Mechanisms of radiation-induced cancer Tissue Modifying Factors Radiation-induced Cancer in Animals Life Shortening Summary Conclusions: Implications for radiation-related cancer at low doses QUANTITATIVE UNCERTAINTY ANALYSIS Overview Sources of uncertainty Allowing for the uncertain possibility of a threshold Conclusions CONCLUSIONS REFERENCES

Contents, preface, executive summary, chapters 1 and 2

Conversion Coefficients for use in Radiological Protection Against External Radiation.

—The coastal belt of Karunagappally, Kerala, India, is known for high background radiation (HBR) from thorium-containing monazite sand. In coastal panchayats, median outdoor radiation levels are more than 4 mGy y−1 and, in certain locations on the coast, it is as high as 70 mGy y−1. Although

Background radiation and cancer incidence in Kerala, India-Karanagappally cohort study.

The objective of the present study was to estimate cancer risk associated with the low-level radiation exposure of an average annual effective dose of 6.4 mSv (including internal exposure) in the high background-radiation areas (HBRA) in Yangjiang, China. The mortality survey consisted of two steps, i.e., the follow-up of cohort members and the ascertainment of causes of death. The cohort members in HBRA were divided into three dose-groups on the basis of environmental dose-rates per year. The mortality experiences of those three dose groups were compared with those in the residents of control areas by means of relative risk (RR). During the period 1987-1995, we observed 926,226 person-years by following up 106,517 subjects in the cohort study, and accumulated 5,161 deaths, among which 557 were from cancers. We did not observe an increase in cancer mortality in HBRA (RR = 0.96, 96% CI, 0.80 to 1.15). The combined data for the period 1979-95 included 125,079 subjects and accumulated 1,698,316 person-years, observed 10,415 total deaths and 1,003 cancer deaths. The relative risk of all cancers for whole HBRA as compared with the control area was estimated to be 0.99 (95% CI, 0.87 to 1.14). The relative risks of cancers of the stomach, colon, liver, lung, bone, female breast and thyroid within whole HBRA were less than one, while the risks for leukemia, cancers of the nasopharynx, esophagus, rectum, pancreas, skin, cervix uteri, brain and central nervous system, and malignant lymphoma were larger than one. None of them were significantly different from RR = 1. Neither homogeneity tests nor trend tests revealed any statistically significant relationship between cancer risk and radiation dose. We did not find any increased cancer risk associated with the high levels of natural radiation in HBRA. On the contrary, the mortality of all cancers in HBRA was generally lower than that in the control area, but not statistically significant.

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Cancer Mortality in the High Background Radiation Areas of Yangjiang, China during the Period between 1979 and 1995

The present study aimed to evaluate the effects of high background radiation (HBR) on mortality. A cohort of 31,604 men and women aged 30-74 y living in the study area in Guangdong Province, China, was followed during the period 1979-1998. The information on deaths and migrations of cohort members was collected by visiting study areas every 3-4 y. Cumulative external radiation dose, lagged by 2 y for leukemia and 10 y for cancer excluding leukemia, was estimated for each individual based on hamlet-specific indoor and outdoor doses, and gender- and age-specific house occupancy factors. The follow-up study accumulated 736,942 person-years at risk and ascertained 6,005 deaths, including 956 cancer deaths and 4,525 non-cancer disease deaths. Mean cumulative radiation doses from natural radiation in the HBR and control area residents were 84.8 mGy and 21.6 mGy, respectively. Mortality due to leukemia (15 deaths) or cancer excluding leukemia (941 deaths) was not related to cumulative radiation dose. The excess relative risk (ERR) Gy of cancer excluding leukemia was estimated to be -1.01 (95% CI: -2.53, 0.95). In site-specific analysis, liver-cancer mortality was inversely related to the cumulative dose (p=0.002). Note, however, that liver cancer is well known for its difficulty in accurate diagnosis. The ERR Gy of cancer excluding leukemia and liver cancer was 0.19 (95% CI: -1.87, 3.04). Non-cancer disease mortality was not related to cumulative radiation dose either. The cumulative HBR dose was not related to the mortality due to cancer or all non-cancer diseases among residents in Yangjiang HBR areas.

Jia Li

Papers

Cancer Mortality in the High Background Radiation Areas of Yangjiang, China during the Period between 1979 and 1995

Cancer and non-cancer mortality among Inhabitants in the high background radiation area of Yangjiang, China (1979-1998).

Noncancer mortality (1987–1995) in high background radiation area of Yangjiang, China