5.1. Cancer Incidence in Atomic Bomb Survivors
Survivors of the atomic bombings of Hiroshima and Nagasaki comprise one of the largest cohorts to study the effect of radiation, with data on about 120 thousand individuals available. There are many published data on the cohort [67
]. A nearly linear relationship exists between cancer incidence and the radiation dose in the high-dose range. On the other hand, it is difficult to draw definite conclusions at low doses. Some reports could not demonstrate a definite increase in cancer incidence in the dose range below 100 mGy [69
], while other data suggested an increase in cancer incidence at the low dose level [70
]. There are also data indicating a decreased cancer incidence at low doses around 50 mGy [71
]. With these contradictory results, therefore, definite conclusions regarding cancer incidence at doses < 100 mGy may be difficult to draw based on data from atomic bomb survivors.
To add to the complicated and confusing situation, a recent report suggested that the doses received by atomic bomb survivors have been largely underestimated [72
]. Historically, the doses from the atomic bombs were estimated from experiments in the Nevada Desert, simulating conditions in Hiroshima and Nagasaki. From the actually measured data, the atomic bomb survivors’ doses were estimated based on the position of each individual at the time of the bombing. Very importantly, however, these estimated doses did not include doses from residual radiation. It has been reported that doses of residual radiation from fallouts of “black rain” that fell within a few days after the bombing were 6–20 mGy in Hiroshima and 120–240 mGy in Nagasaki [73
]; however, people who came into the hypocenter of Hiroshima complained of severe symptoms of radiation sickness [72
], and such symptoms never occur below a dose of 200 mGy. Many people who were outside of the exposed area came into the cities and were irradiated from the residual radiation, but their data were used as controls. Other data in Nagasaki also indicate the importance of fallout radiation in estimating the hazard of atomic bombs [74
]. To summarize, the doses of the atomic bomb survivors receiving low doses (< 100 mGy) may have been largely underestimated, so many of those who were considered to have received low doses may have received much higher doses. Hence, they are not low-dose survivors. Furthermore, many control people who were not directly exposed to radiation from the bombs but entered the exposed area after bombing had received non-negligible amounts of residual radiation. Therefore, those people are inappropriate as controls. Thus, no conclusions can be drawn regarding the effects of low-dose radiation from the data on atomic bomb survivors.
5.2. Lifespan and Cancer Mortality/Incidence by Low-Level Radiation Exposure
Many studies have examined this issue. Most of them are anecdotal and some should be criticized. Several studies investigated the relationship between cancer incidence or mortality and amounts of natural background radiation [2
]. They indicated that higher background levels were associated with lower cancer incidences and mortality rates. This may be due to the hormetic effects of low-dose radiation, but it has been pointed out that regions with high background radiation are usually at a high altitude, and so air pollution problems are less severe. Therefore, this inverse correlation may not necessarily be due to the natural background radiation.
In Japan, there is a report that inhabitants of the Misasa spa area, famous for radon production, had low cancer mortality rates; in particular, lung cancer mortality was much lower than that of the Japanese average [76
]. Such decreases in cancer mortality were not observed in inhabitants of the Beppu spa area where radon levels are much lower [77
]. Therefore, this observation in Misasa people was suggested to be due to radon inhalation, resulting in a hormetic effect. Six years later, another report was published regarding cancer mortality in the Misasa area; the inhabitants were divided into two groups according to the radon levels in their houses, but there was no difference in cancer mortality between the high- and low-level radon groups [78
]. Thus, the optimal level of radon was not clarified and the hormetic effect was unclear. The subjects of the two investigations on Misasa inhabitants were different, and they were not necessarily contradictory. Subsequent investigations showed that Misasa inhabitants had a low mortality rate due to gastric cancer [79
]. Regarding the association between radon inhalation (average radon concentrations in homes) and cancer mortality, a study from the United States showed that there was a strong tendency for lung cancer rates to decrease with increasing radon exposure [80
]. Thus, the study failed to support the LNT theory for carcinogenesis.
In Taiwan, a low cancer mortality rate was reported in residents of apartments contaminated with Cobalt-60, but in that study, the control group was not matched to the residents in the building [81
]. A subsequent study corrected the erroneous result, and did not suggest a lower risk for the low-dose irradiated inhabitants [82
A number of studies investigated the cancer incidence or mortality in people occupationally exposed to low-dose radiation. A report on nuclear industry workers from 15 countries suggested an overall increase in cancer mortality, but when the studied countries were analyzed separately, only the data from Canada showed an exceptionally high mortality rate; data from the other 14 countries did not show significant increases in cancer mortality [83
]. In addition, the reliability of the Canadian data was questioned, and thus, no meaningful conclusion could be drawn from that study. Moreover, other data came from the UK on the cancer incidence of nuclear workers, and this newer study suggested a trend towards a decreased cancer mortality rate in workers receiving total doses < 50 mGy [84
]. More recently, similar analyses of nuclear workers in France, the United Kingdom, and the United States were published as the INWORKS study. The data suggested a nearly linear increase in the incidence of leukemia, lymphoma, and other cancers with radiation dose, and the LNT hypothesis appeared to fit the data [85
]. However, the increases mostly did not seem to be significant below the dose of 100 mGy, and in addition, many objections have been raised [87
]. The criticisms include the lack of a negative control, use of 90% confidence intervals (instead of 95%) and one-tailed test, and no consideration of natural background radiation and smoking. Therefore, the INWORKS study also may not be supportive of the LNT hypothesis.
It is well known that high in the atmosphere, radiation levels from cosmic rays are marked, and pilots and cabin attendants are exposed to excessive natural radiation. A study of 19,184 male European pilots showed that cancer mortality of the pilots was lower than that of age-matched controls and the decrease was more marked in those receiving higher levels of radiation [89
]. They were estimated to have received 2–5 mSv of radiation per year to the whole body. These lower cancer mortality rates in pilots and nuclear workers may be, in part, explained by healthy worker effects, and the decrease cannot solely be attributable to the effects of low-dose radiation exposure.
In the UK, the mortality of radiologists who registered with the radiological society since 1897 was studied [90
]. British radiologists who registered before 1954 until when radiation protection was not strictly regulated had been exposed to high levels of radiation, and cancer mortality was high. Radiologists who registered after 1955 had lower radiation exposure owing to more attention being paid to radioprotection, and as a result, they received much lower radiation doses; they had about 30% lower cancer mortality, compared with other specialty doctors and people of similar social classes. Recently, the mortality of interventional radiologists was compared with that of psychiatrists, and interventional radiologists were found to have a 20% lower mortality and a low rate of cancer deaths (8% for male and 17% for female radiologists) [91
]. It is interesting that this paper was published by the group who had previously supported the LNT hypothesis. These data should also be evaluated in relation to many confounding factors.
5.3. Effects of Radiation from Computed Tomography
At least two papers have been published suggesting an increase in cancer (including benign tumors) incidence in individuals undergoing CT during childhood [92
]. Soon after publication, these studies were heavily criticized; comparing the two groups with or without CT during childhood was illogical because the CT groups contained cancer-prone individuals [94
]. Thereafter, the authors of the paper excluded patients with cancer-prone syndromes such as Down syndrome and Noonan syndrome, and again reported that there were still differences between the two groups [96
]. Nevertheless, such exclusion of high-risk individuals does not lead to complete elimination of the biases between the two groups. Children who undergo CT are quite different from those who do not. Do completely healthy children undergo CT? The answer is of course no, which every clinician knows. Such biased studies are merely misleading and of no value.
There is a well-known American study (National Lung Screening Trial) that investigated the efficacy of lung screening by CT in former heavy smokers [97
]. The study subjects were randomly divided into a CT screening group and chest radiography screening group, and both examinations were performed three times per year. As a result, the CT group had a 20% lower cancer mortality and a 7% lower overall mortality compared with the chest radiography group. The aim of this study was not to examine the adverse effects of CT screening; however, from the results, it is concluded that CT conducted three times a year does not have a negative effect.
An interesting case report was recently published [98
]. A patient with severe Alzheimer’s disease underwent serial CT, and as a result, she showed marked improvement in her symptoms. The attending doctor and medical staffs could identify no causes of her improvement other than CT. Her husband with Parkinson’s disease also underwent repeat CT scans, and he also noticed a marked recovery of his symptoms. Such an experience may be prospectively examined in view of the marked increase in the incidence of Alzheimer’s disease, and we are considering this as a future strategy.
5.4. Randomized Human Studies on the Effects of Low-Dose-Radiation-Emitting Mats
In the last section of this article, we introduce unpublished data from Prof. Norinaga Shimizu (Osaka Prefectural University, Osaka, Japan) on a human study investigating the effects of a low-dose-radiation-emitting mat (hormesis mat), with permission from Dr. Shimizu. This was presented at the Japanese Society for Radiation Oncology Symposium for Cancer Control (Nagoya, Japan, 17 June 2017) but it will not be published in English. Low-dose-radiation-emitting mats were manufactured by Aoyama Stein Co., Ltd. (Kobe, Japan). The raw materials are the same as those used for the sheets employed in the experiments involving silkworms (Figure 2
), and the sheets contain 228
Ac and 77
Br. The dose rate was 5 μGy/h for γ rays (measured by a survey meter) on the surface of the mats. Control (placebo) mats with the same physical property but no radioisotopes were also manufactured.
Sixty healthy volunteers (30 men and 30 women) with a median age of 32 years (range, 22–48) were randomly divided into a hormesis mat group (15 men and women) and placebo group (15 men and women). They were instructed to sleep on the mats every day. The volunteers underwent medical and physical checkups, and their serum reactive oxygen species levels were measured. The reactive oxygen levels at 3 months after starting the experiment were 3.1 and 9.4% lower on average than the initial levels in the placebo and hormesis mat groups, respectively, in men, and 3.1 and 8.5% lower, respectively, in women (both p < 0.05). Sleep latency and the physical, psychological, and neurosensory status were all improved in the hormesis mat group compared with the placebo group.
Doctor Shimizu’s group conducted another randomized study with 40 male volunteers. They were instructed to sleep on the hormesis or placebo mats. Increases in salivary immunoglobulin A and elongation of the slow-wave sleep (deep sleep) period were observed in the hormesis mat group. Thus, the studies by Dr. Shimizu and colleagues demonstrated that continuous low-dose radiation during sleep yielded beneficial effects from various aspects.