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Concept: Hiroshima

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This is the third analysis of solid cancer incidence among the Life Span Study (LSS) cohort of atomic bomb survivors in Hiroshima and Nagasaki, adding eleven years of follow-up data since the previously reported analysis. For this analysis, several changes and improvements were implemented, including updated dose estimates (DS02R1) and adjustment for smoking. Here, we focus on all solid cancers in aggregate. The eligible cohort included 105,444 subjects who were alive and had no known history of cancer at the start of follow-up. A total of 80,205 subjects had individual dose estimates and 25,239 were not in either city at the time of the bombings. The follow-up period was 1958-2009, providing 3,079,484 person-years of follow-up. Cases were identified by linkage with population-based Hiroshima and Nagasaki Cancer Registries. Poisson regression methods were used to elucidate the nature of the radiation-associated risks per Gy of weighted absorbed colon dose using both excess relative risk (ERR) and excess absolute risk (EAR) models adjusted for smoking. Risk estimates were reported for a person exposed at age 30 years with attained age of 70 years. In this study, 22,538 incident first primary solid cancer cases were identified, of which 992 were associated with radiation exposure. There were 5,918 cases (26%) that occurred in the 11 years (1999-2009) since the previously reported study. For females, the dose response was consistent with linearity with an estimated ERR of 0.64 per Gy (95% CI: 0.52 to 0.77). For males, significant upward curvature over the full dose range as well as restricted dose ranges was observed and therefore, a linear-quadratic model was used, which resulted in an ERR of 0.20 (95% CI: 0.12 to 0.28) at 1 Gy and an ERR of 0.010 (95% CI: -0.0003 to 0.021) at 0.1 Gy. The shape of the ERR dose response was significantly different among males and females (P = 0.02). While there was a significant decrease in the ERR with increasing attained age, this decrease was more rapid in males compared to females. The lowest dose range that showed a statistically significant dose response using the sex-averaged, linear ERR model was 0-100 mGy (P = 0.038). In conclusion, this analysis demonstrates that solid cancer risks remain elevated more than 60 years after exposure. Sex-averaged upward curvature was observed in the dose response independent of adjustment for smoking. Findings from the current analysis regarding the dose-response shape were not fully consistent with those previously reported, raising unresolved questions. At this time, uncertainties in the shape of the dose response preclude definitive conclusions to confidently guide radiation protection policies. Upcoming results from a series of analyses focusing on the radiation risks for specific organs or organ families, as well as continued follow-up are needed to fully understand the nature of radiation-related cancer risk and its public health significance. Data and analysis scripts are available for download at: http://www.rerf.or.jp .

Concepts: Regression analysis, Epidemiology, Cancer, Ionizing radiation, Relative risk, Nuclear weapon, Atomic bombings of Hiroshima and Nagasaki, Hiroshima

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Seventy years ago, the medical profession alerted the world to the devastating effects of nuclear weapons. Just weeks after the bombing of Hiroshima, Dr. Marcel Junod, a representative of the International Committee of the Red Cross in Japan, visited the devastated city and sent back one of the first eyewitness reports to reach the outside world: “The center of the city was a sort of white patch, flattened and smooth like the palm of a hand. Nothing remained.” Ever since that time, members of the medical profession have played a key role in warning governments and the public about the . . .

Concepts: Uranium, Nuclear weapon, World War II, Atomic bombings of Hiroshima and Nagasaki, Nuclear warfare, Hiroshima, Plutonium, Little Boy

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Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the ‘integrate-and-fire’ algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to (239)Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation-environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking.

Concepts: DNA, Cancer, Ionizing radiation, Neural network, Nuclear weapon, Background radiation, Atomic bombings of Hiroshima and Nagasaki, Hiroshima

3

Thyroid cancer is one of the major health concerns after the accident in the Fukushima Dai-ichi nuclear power station (NPS). Currently, ultrasonography surveys are being performed for persons residing in the Fukushima Prefecture at the time of the accident with an age of up to 18 years. Here, the expected thyroid cancer prevalence in the Fukushima Prefecture is assessed based on an ultrasonography survey of Ukrainians, who were exposed at an age of up to 18 years to (131)I released during the Chernobyl NPS accident, and on differences in equipment and study protocol in the two surveys. Radiation risk of thyroid cancer incidence among survivors of the atomic bombings of Hiroshima and Nagasaki and preliminary estimates of thyroid dose due to the Fukushima accident were used for the prediction of baseline and radiation-related thyroid cancer risks. We estimate a prevalence of thyroid cancer of 0.027 % (95 % CI 0.010 %; 0.050 %) for the first screening campaign in the Fukushima Prefecture. Compared with the incidence rate in Japan in 2007, the ultrasonography survey is predicted to increase baseline thyroid cancer incidence by a factor of 7.4 (95 % CI 0.95; 17.3). Under the condition of continued screening, thyroid cancer during the first fifty years after the accident is predicted to be detected for about 2 % of the screened population. The prediction of radiation-related thyroid cancer in the most exposed fraction (a few ten thousand persons) of the screened population of the Fukushima Prefecture has a large uncertainty with the best estimates of the average risk of 0.1-0.3 %, depending on average dose.

Concepts: Cancer, Uranium, Atomic bombings of Hiroshima and Nagasaki, Hiroshima, Nagasaki, Little Boy, Fat Man, Potsdam Declaration

2

To fully understand the radiation effects of the atomic bombing of Hiroshima and Nagasaki among the survivors, radiation from neutron-induced radioisotopes in soil and other materials should be considered in addition to the initial radiation directly received from the bombs. This might be important for evaluating the radiation risks to the people who moved to these cities soon after the detonations and probably inhaled activated radioactive “dust.” Manganese-56 is known to be one of the dominant radioisotopes produced in soil by neutrons. Due to its short physical half-life, (56)Mn emits residual radiation during the first hours after explosion. Hence, the biological effects of internal exposure of Wistar rats to (56)Mn were investigated in the present study. MnO2 powder was activated by a neutron beam to produce radioactive (56)Mn. Rats were divided into four groups: those exposed to (56)Mn, to non-radioactive Mn, to (60)Co γ rays (2 Gy, whole body), and those not exposed to any additional radiation (control). On days 3, 14, and 60 after exposure, the animals were killed and major organs were dissected and subjected to histopathological analysis. As described in more detail by an accompanying publication, the highest internal radiation dose was observed in the digestive system of the rats, followed by the lungs. It was found that the number of mitotic cells increased in the small intestine on day 3 after (56)Mn and (60)Co exposure, and this change persisted only in (56)Mn-exposed animals. Lung tissue was severely damaged only by exposure to (56)Mn, despite a rather low radiation dose (less than 0.1 Gy). These data suggest that internal exposure to (56)Mn has a significant biological impact on the lungs and small intestine.

Concepts: Cancer, Ionizing radiation, Neutron, Digestion, Nuclear weapon, Atomic bombings of Hiroshima and Nagasaki, Hiroshima, Nagasaki

0

The Japan NBI Expert Team (JNET) was organized to unify four previous magnifying NBI classifications (the Sano, Hiroshima, Showa, and Jikei classifications). The JNET working group created criteria (referred to as the NBI scale) for evaluation of vessel pattern (VP) and surface pattern (SP). We conducted a multicenter validation study of the NBI scale to develop the JNET classification of colorectal lesions.

Concepts: Hiroshima

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In the Life Span Study of atomic bomb survivors, differences in urbanicity between high-dose and low-dose survivors could confound the association between radiation dose and adverse outcomes. We obtained data on the pre-bombing population distribution in Hiroshima and Nagasaki, and quantified the impact of adjustment for population density on radiation risk estimates for mortality (1950-2003) and incident solid cancer (1958-2009). Population density ranged from 4,671-14,378 and 5,748-19,149 people/km2 in urban regions of Hiroshima and Nagasaki, respectively. Radiation risk estimates for solid cancer mortality were attenuated by 5.1%, but those for all-cause mortality and incident solid cancer were unchanged. There was no overall association between population density and adverse outcomes, but there was evidence that the association between density and mortality differed by age at exposure. Among survivors 10-14 years old in 1945, there was a positive association between population density and risk of all-cause mortality (relative risk, 1.053 per 5,000 people/km2 increase, 95% confidence interval: 1.027, 1.079) and solid cancer mortality (relative risk, 1.069 per 5,000 people/km2 increase, 95% confidence interval: 1.025, 1.115). Our results suggest that radiation risk estimates from the Life Span Study are not sensitive to unmeasured confounding by urban-rural differences.

Concepts: Cancer, Ionizing radiation, Demography, Population, Population density, Nuclear weapon, Atomic bombings of Hiroshima and Nagasaki, Hiroshima

0

Orthopaedic surgeons are routinely exposed to intraoperative radiation and, therefore, follow the principle of “as low as reasonably achievable” with regard to occupational safety. However, standardized education on the long-term health effects of radiation and the basis for current radiation exposure limits is limited in the field of orthopaedics. Much of orthopaedic surgeons' understanding of radiation exposure limits is extrapolated from studies of survivors of the atomic bombings in Hiroshima and Nagasaki, Japan. Epidemiologic studies on cancer risk in surgeons and interventional proceduralists and dosimetry studies on true radiation exposure during trauma and spine surgery recently have been conducted. Orthopaedic surgeons should understand the basics and basis of radiation exposure limits, be familiar with the current literature on the incidence of solid tumors and cataracts in orthopaedic surgeons, and understand the evidence behind current intraoperative fluoroscopy safety recommendations.

Concepts: Epidemiology, Cancer, Nuclear weapon, Atomic bombings of Hiroshima and Nagasaki, Hiroshima, Hibakusha, Nagasaki, Little Boy

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Despite ongoing tensions in various parts of the world, the year 2017 ended on a positive note. The Treaty Prohibiting Nuclear Weapons (TPNW) was passed by the UN General Assembly on July 7, 2017, which will always be a red-letter day in history. It has raised many hopes for a future world without nuclear weapons and staved off the impending humanitarian catastrophe. Good health is a basic need of every individual. Therefore, each person yearns for a life free of violence and free of man-made catastrophes like the ones at Hiroshima and Nagasaki in 1945, which killed over two hundred thousand people and resulted in genetic mutations affecting generations thereafter. Unfortunately, instead of working for nuclear disarmament, the world moved towards an unending nuclear arms race, costing billions which could have been used for healing millions of people living in despair and sickness. This is why on December 10, 2017, Oslo, the capital of Norway, was filled with excitement when the Nobel Peace Prize for this year was bestowed upon the International Campaign to Abolish Nuclear Weapons (ICAN). Large numbers of medical professionals from around the globe had gathered there to affirm their commitment to a healthy future through diversion of wasteful expenditure from the nuclear arms race towards universal health.

Concepts: Nuclear weapon, Cold War, Nobel Prize, Nobel Peace Prize, Atomic bombings of Hiroshima and Nagasaki, Nuclear warfare, Hiroshima, Nuclear disarmament

0

After the atomic bombing of Hiroshima and Nagasaki, long-term epidemiological studies were undertaken on the irradiated survivors and their offspring, and are still underway. These thorough studies involving tens of thousands of persons and published in hundreds of papers have shown a moderate increase in cancer incidence for irradiated survivors, with limited impact on their life span (loss of one year at most). In studies on the offspring of these survivors, no statistically significant deleterious effect on malformation frequency, incidence of mutations or mortality from cancer and other diseases has been seen so far. These data are actually the basis for current radiation safety levels; they show that health risks from radiation are limited, but they are not applicable to complex situations such as nuclear power station accidents that involve diverse types of radiation as well as contamination by radioactive materials.

Concepts: Epidemiology, Cancer, Uranium, Nuclear weapon, Lists of nuclear disasters and radioactive incidents, Atomic bombings of Hiroshima and Nagasaki, Hiroshima, Plutonium