Young people's perspectives of thyroid cancer screening and its harms after the nuclear accident in Fukushima Prefecture: a questionnaire survey indicating opt-out screening strategy of the thyroid examination as an ethical issue.

BACKGROUND: Overdiagnosis of thyroid cancer has become a major global medical issue. Ultrasound-based thyroid cancer screening has promoted overdiagnosis, and recently international recommendations state that it should not be conducted, even after a nuclear accident. The Fukushima thyroid cancer screening program was initiated in 2011 as a health policy after the nuclear accident. The risk of radiation-induced thyroid cancer was unlikely given the low radiation levels, but the thyroid cancer screening program has continued at 2-year intervals with a relatively high participation rate and is now in its fifth round. It is therefore crucial to clarify whether those targeted for screening understand the disadvantages of screening, and to identify factors that influenced their decision to participate. METHODS: We conducted an anonymous mail-based questionnaire among young people from Fukushima Prefecture (subjects) and a neighboring prefecture that was not targeted for screening (non-subjects). We asked them about the significance of the thyroid cancer screening in Fukushima Prefecture, their reasons for accepting or refusing screening, their perception of the harms of screening, and their opinions on thyroid examination at school. We compared the results of the questionnaire between subjects and non-subjects and between examinees (who were screened) and non-examinees (who declined screening). RESULTS: Only 16.5% of respondents were aware of the harms associated with thyroid cancer screening, with most perceiving that the benefits outweighed the harms. Comparison of subjects' and non-subjects' responses showed there were no significant differences between the two groups. Among subjects, there were also no differences in responses between examinees and non-examinees. The most common reason for participation in screening was that the screening was conducted in schools and perceived as obligatory. CONCLUSIONS: These results highlighted a serious ethical issue in that school-based screening leads to making young people think that it is mandatory screening in an opt-out and default setting manner, with a lack of knowledge about the disadvantages of screening. Based on the autonomy of the subjects and the ethical principle of the post-disaster, surveys after a nuclear disaster should be conducted in an opt-in style without an opt-out style such as school-based screening.

Cover up and cancer risk assessment: Prominent US scientists suppressed evidence to promote adoption of LNT.

This paper reports that William Russell, Oak Ridge National Laboratory (ORNL), conducted a large-scale lifetime study from 1956 to 1959 showing that exposure of young adult male mice to a large dose of acute X-rays had no treatment effects on male and female offspring concerning longevity or the frequency, severity, or age distribution of neoplasms and other diseases. Despite the scientific, societal and crucial timing significance of the study, Russell did not publish the findings for almost 35 years, nor did he inform governmental advisory committees, thereby significantly biasing decisions made during this period which supported the adoption of LNT for risk assessment. Of further significance, Arthur Upton, an ORNL colleague of Russell during this study and later Director of the US National Cancer Institute (NCI), was also fully knowledgeable of this study, its findings and its negative impact on the acceptance of LNT. Upton later worked along with Russell to publish these data (i.e., Cosgrove et al., 1993) to dispute the case-specific claim that children developed cancer because of the radiation exposure of their fathers as workers at the Sellafield nuclear plant. Thus, while Russell's data were available, but were not used to challenge the key radiation and leukemia paper of Edward B. Lewis, (1957) when LNT was being adopted by regulatory agencies, they were used in a major trial in the United Kingdom (UK) for the client (i.e., British Nuclear Fuels Plc) that hired Upton. While the duplicity of Russell's and Upton's actions is striking, the key finding of the present paper is that Russell and Upton intentionally orchestrated and sustained an LNT cover up during the key period of LNT adoption by regulatory agencies, thereby showing an overwhelming bias to enhance the adoption of LNT.

The threshold vs LNT showdown: Dose rate findings exposed flaws in the LNT model part 1. The Russell-Muller debate.

This paper assesses the discovery of the dose-rate effect in radiation genetics and how it challenged fundamental tenets of the linear non-threshold (LNT) dose response model, including the assumptions that all mutational damage is cumulative and irreversible and that the dose-response is linear at low doses. Newly uncovered historical information also describes how a key 1964 report by the International Commission for Radiological Protection (ICRP) addressed the effects of dose rate in the assessment of genetic risk. This unique story involves assessments by two leading radiation geneticists, Hermann J. Muller and William L. Russell, who independently argued that the report's Genetic Summary Section on dose rate was incorrect while simultaneously offering vastly different views as to what the report's summary should have contained. This paper reveals occurrences of scientific disagreements, how conflicts were resolved, which view(s) prevailed and why. During this process the Nobel Laureate, Muller, provided incorrect information to the ICRP in what appears to have been an attempt to manipulate the decision-making process and to prevent the dose-rate concept from being adopted into risk assessment practices.

The threshold vs LNT showdown: Dose rate findings exposed flaws in the LNT model part 2. How a mistake led BEIR I to adopt LNT.

This paper reveals that nearly 25 years after the National Academy of Sciences (NAS), Biological Effects of Ionizing Radiation (BEIR) I Committee (1972) used Russell's dose-rate data to support the adoption of the linear-no-threshold (LNT) dose response model for genetic and cancer risk assessment, Russell acknowledged a significant under-reporting of the mutation rate of the historical control group. This error, which was unknown to BEIR I, had profound implications, leading it to incorrectly adopt the LNT model, which was a decision that profoundly changed the course of risk assessment for radiation and chemicals to the present.

Lessons to be learned from a contentious challenge to mainstream radiobiological science (the linear no-threshold theory of genetic mutations).

There are both statistically valid and invalid reasons why scientists with differing default hypotheses can disagree in high-profile situations. Examples can be found in recent correspondence in this journal, which may offer lessons for resolving challenges to mainstream science, particularly when adherents of a minority view attempt to elevate the status of outlier studies and/or claim that self-interest explains the acceptance of the dominant theory. Edward J. Calabrese and I have been debating the historical origins of the linear no-threshold theory (LNT) of carcinogenesis and its use in the regulation of ionizing radiation. Professor Calabrese, a supporter of hormesis, has charged a committee of scientists with misconduct in their preparation of a 1956 report on the genetic effects of atomic radiation. Specifically he argues that the report mischaracterized the LNT research record and suppressed calculations of some committee members. After reviewing the available scientific literature, I found that the contemporaneous evidence overwhelmingly favored a (genetics) LNT and that no calculations were suppressed. Calabrese's claims about the scientific record do not hold up primarily because of lack of attention to statistical analysis. Ironically, outlier studies were more likely to favor supra-linearity, not sub-linearity. Finally, the claim of investigator bias, which underlies Calabrese's accusations about key studies, is based on misreading of text. Attention to ethics charges, early on, may help seed a counter narrative explaining the community's adoption of a default hypothesis and may help focus attention on valid evidence and any real weaknesses in the dominant paradigm.

Consequences of the radiation accident at the Mayak production association in 1957 (the 'Kyshtym Accident').

This paper presents an overview of the nuclear accident that occurred at the Mayak Production Association (PA) in the Russian Federation on 29 September 1957, often referred to as 'Kyshtym Accident', when 20 MCi (740 PBq) of radionuclides were released by a chemical explosion in a radioactive waste storage tank. 2 MCi (74 PBq) spread beyond the Mayak PA site to form the East Urals Radioactive Trace (EURT). The paper describes the accident and gives brief characteristics of the efficacy of the implemented protective measures that made it possible to considerably reduce doses to the exposed population. The paper also provides retrospective dosimetry estimates for the members of the EURT Cohort (EURTC) which comprises approximately 21 400 people. During the first two years after the accident a decrease in the group average leukocyte (mainly due to neutrophils and lymphocytes) and thrombocyte count was observed in the population. At later dates an increased excess relative risk of solid cancer incidence and mortality was found in the EURTC.

Simulation-extrapolation method to address errors in atomic bomb survivor dosimetry on solid cancer and leukaemia mortality risk estimates, 1950-2003.

Analyses of the Life Span Study (LSS) of Japanese atomic bombing survivors have routinely incorporated corrections for additive classical measurement errors using regression calibration. Recently, several studies reported that the efficiency of the simulation-extrapolation method (SIMEX) is slightly more accurate than the simple regression calibration method (RCAL). In the present paper, the SIMEX and RCAL methods have been used to address errors in atomic bomb survivor dosimetry on solid cancer and leukaemia mortality risk estimates. For instance, it is shown that using the SIMEX method, the ERR/Gy is increased by an amount of about 29 % for all solid cancer deaths using a linear model compared to the RCAL method, and the corrected EAR 10(-4) person-years at 1 Gy (the linear terms) is decreased by about 8 %, while the corrected quadratic term (EAR 10(-4) person-years/Gy(2)) is increased by about 65 % for leukaemia deaths based on a linear-quadratic model. The results with SIMEX method are slightly higher than published values. The observed differences were probably due to the fact that with the RCAL method the dosimetric data were partially corrected, while all doses were considered with the SIMEX method. Therefore, one should be careful when comparing the estimated risks and it may be useful to use several correction techniques in order to obtain a range of corrected estimates, rather than to rely on a single technique. This work will enable to improve the risk estimates derived from LSS data, and help to make more reliable the development of radiation protection standards.

Epidemiological studies of lung carcinoma incidence in uranium miners (accumulation and retrospective use of diagnostic data).

The paper attracts attention to the question of accumulation and retrospective use of diagnostic data in the early epidemiological studies of lung carcinoma incidence in uranium miners in Schneeberg, Saxony, and in Jáchymov (Joachimsthal), Bohemia.

Public health, racial tensions, and body politic: mass ringworm irradiation in Israel, 1949-1960.

In this essay, we analyze the case study of mass ringworm irradiation conducted in Israel during its first years of existence and its consequences. We analyzed the case study of ringworm irradiation in the framework of racial construction of illness and its treatment, showing the elasticity of race and ethnicity as medical and social categories.

Assessing cancer risk factors faced by an Ancestral Puebloan population in the North American Southwest.

Ancestral Puebloan people in the North American Southwest suffered high rates of disease, poor health, and early age-at-death. Four individuals with skeletal expressions of cancer were found in a pre-Columbian population in the Taos Valley - Reports of malignant neoplasms in the archaeological record are uncommon and their presence in four of 82 individuals is a high occurrence. This study continues Whitley and Boyer's (2012) research testing whether concentrations of ionizing radiation were sufficiently high to induce cancer and related health issues. Access to a preserved and partly reconstructed subterranean pit structure inhabited between AD 1120 and 1170, allows us to test radon concentrations in a residential dwelling. This study found radon occurring in high levels, 19.4-20.3 pCi/L (717.8-751.1 Bq/m3) within the structure. Epidemiological reports are inconsistent when linking specific cancers and radon exposure. However, this study can control for many of the confounding factors plaguing other studies, provide unique data that have the potential to initiate dialogue on the etiology of neoplastic disease in the American Southwest, and add new dimensions to the study of the living conditions and health of the Ancestral Puebloans and their descendants.

Residential radon and lung cancer: end of the story?

The earliest evidence of increased lung cancer risk associated with radon came largely from studies of highly exposed underground miners. In the United States, concerns about residential exposures became prominent in the early 1980s with the identification of the Watras home, which had remarkably elevated radon concentrations. By then, the problem of indoor radon was already recognized in Europe and the first epidemiological studies on indoor radon had been reported. The concern about the risk of indoor radon motivated a series of case-control studies of residential radon and lung cancer in the United States, Canada, China, and a number of European countries. In 1999, the U.S. National Research Council Committee on the Biological Effects of Ionizing Radiation (BEIR VI) weighed the scientific evidence available at that time on this issue and concluded that residential radon was an important contributor to the lung cancer burden and that risks were appropriately estimated by a linear nonthreshold model. Since individual case-control studies have not provided consistent direct evidence of excess lung cancer risk at residential exposure levels, combined analyses of residential radon studies have been undertaken in both North America and Europe. These combined analyses, including the North American pooled analysis described in this issue, represent an important complement to the findings of the miner studies and further support the linear no-threshold model for cancer risk adopted by the BEIR VI Committee and other groups.

The historical aspects of photocarcinogenesis.

The concept of photocarcinogenesis is of fairly recent duration. Although cancer of the breast is described in the ancient Greek medical literature, skin cancer is not mentioned even as late as the 18th Century. This is most likely due to the poor survival of humans, 80% of people did not live past 40 years, and only 6% lived longer than 60 years. The first association of skin cancer (face and lip) with outdoor exposure dates to the middle of the 19th Century. About that time it was shown that it was Ultraviolet Radiation (UVR) that could cause skin and eye inflammation. It was not until the 20th Century that competent epidemiologic studies associated human skin cancer with chronic solar exposure, and it was shown that chemicals could augment the effects of UVR exposure. It has only been in the last quarter of a Century that it was found that UVR could cause immunologic changes that allow multiple skin cancers to develop. Advances in molecular biology have begun to show the cellular and molecular events that lead to UVR induced skin carcinogenesis.

Radiation Research Society. 1952-2002. Historical and current highlights in radiation biology: has anything important been learned by irradiating cells?

Around 30 years ago, a very prominent molecular biologist confidently proclaimed that nothing of fundamental importance has ever been learned by irradiating cells! The poor man obviously did not know about discoveries such as DNA repair, mutagenesis, connections between mutagenesis and carcinogenesis, genomic instability, transposable genetic elements, cell cycle checkpoints, or lines of evidence historically linking the genetic material with nucleic acids, or origins of the subject of oxidative stress in organisms, to name a few things of fundamental importance learned by irradiating cells that were well known even at that time. Early radiation studies were, quite naturally, phenomenological. They led to the realization that radiations could cause pronounced biological effects. This was followed by an accelerating expansion of investigations of the nature of these radiobiological phenomena, the beginnings of studies aimed toward better understanding the underlying mechanisms, and a better appreciation of the far-reaching implications for biology, and for society in general. Areas of principal importance included acute tissue and tumor responses for applications in medicine, whole-body radiation effects in plants and animals, radiation genetics and cytogenetics, mutagenesis, carcinogenesis, cellular radiation responses including cell reproductive death, cell cycle effects and checkpoint responses, underlying molecular targets leading to biological effects, DNA repair, and the genetic control of radiosensitivity. This review summarizes some of the highlights in these areas, and points to numerous examples where indeed, many things of considerable fundamental importance have been learned by irradiating cells.

26th Lauriston S. Taylor Lecture: developing mechanistic data for incorporation into cancer and genetic risk assessments: old problems and new approaches.

The theme that runs through this 26th Taylor Lecture is the question of how can data on the mechanism of induction of genetic alterations by radiations and chemicals be used to support the development of risk estimates, particularly at low exposure levels. The premise is that chromosomal alterations are involved in the development of tumors and birth defects, and that data generated for genetic alterations can be interpreted in terms of these adverse health outcomes. The general conclusions are that chromosomal alterations can be induced by ionizing radiations by a single energy loss event in a target of the size of a DNA molecule and that aberrations generally result from misrepair or failure to repair the induced lesions (generally assumed to be double-strand breaks). Chromosomal alterations induced by chemicals are produced almost exclusively by replication errors on a damaged DNA template. Thus, cell cycle stage and DNA repair and replication fidelity will be influential on overall sensitivity to aberration induction. These same features are also important in considerations of genetic susceptibility-alterations in cell cycle control or DNA repair or replication fidelity can alter sensitivity. The differences in mechanism of induction of chromosomal aberrations by ionizing radiation and chemicals is most important when considering cells at risk and comparative sensitivities among species and cell types. Models of cancer induction have gradually evolved from initiation, promotion, and progression models to multistep genetic models to the most recent one of six acquired characteristics. This evolution has passed the level of concentration of research from single gene, single cell to multiple genes (pathways), and whole tissues. The latter areas of concentration are ideal for addressing with the new genomics, proteomics, and computational modeling approaches. The attention is still on the role of genetic alterations in cancer and hereditary effects and the mechanism of their formation--it is the approaches to address these that are changing.