Preston, D. L., Ron, E., Tokuoka, S., Funamoto, S., Nishi, N., Soda, M., Mabuchi, K. and Kodama, K. Solid Cancer Incidence in Atomic Bomb Survivors: 1958–1998. Radiat. Res. 168, 1–64 (2007). This is the second general report on radiation effects on the incidence of solid cancers (cancers other than malignancies of the blood or blood-forming organs) among members of the Life Span Study (LSS) cohort of Hiroshima and Nagasaki atomic bomb survivors. The analyses were based on 17,448 first primary cancers (including non-melanoma skin cancer) diagnosed from 1958 through 1998 among 105,427 cohort members with individual dose estimates who were alive and not known to have had cancer prior to 1958. Radiation-associated relative risks and excess rates were considered for all solid cancers as a group, for 19 specific cancer sites or groups of sites, and for five histology groups. Poisson regression methods were used to investigate the magnitude of the radiation-associated risks, the shape of the dose respon...

https://bioone.org/journals/Radiation-Research/volume-168/issue-1/RR0763.1/Solid-Cancer-Incidence-in-Atomic-Bomb-Survivors-19581998/10.1667/RR0763.1.pdf

Solid Cancer Incidence in Atomic Bomb Survivors: 1958–1998

Sources, Effects and Risks of Ionizing Radiation

ContextComputed tomography coronary angiography (CTCA) has become a common diagnostic test, yet there are little data on its associated cancer risk. The recent Biological Effects of Ionizing Radiation (BEIR) VII Phase 2 report provides a framework for estimating lifetime attributable risk (LAR) of cancer incidence associated with radiation exposure from a CTCA study, using the most current data available on health effects of radiation.ObjectivesTo determine the LAR of cancer incidence associated with radiation exposure from a 64-slice CTCA study and to evaluate the influence of age, sex, and scan protocol on cancer risk.Design, Setting, and PatientsOrgan doses from 64-slice CTCA to standardized phantom (computational model) male and female patients were estimated using Monte Carlo simulation methods, using standard spiral CT protocols. Age- and sex-specific LARs of individual cancers were estimated using the approach of BEIR VII and summed to obtain whole-body LARs.Main Outcome MeasuresWhole-body and organ LARs of cancer incidence.ResultsOrgan doses ranged from 42 to 91 mSv for the lungs and 50 to 80 mSv for the female breast. Lifetime cancer risk estimates for standard cardiac scans varied from 1 in 143 for a 20-year-old woman to 1 in 3261 for an 80-year-old man. Use of simulated electrocardiographically controlled tube current modulation (ECTCM) decreased these risk estimates to 1 in 219 and 1 in 5017, respectively. Estimated cancer risks using ECTCM for a 60-year-old woman and a 60-year-old man were 1 in 715 and 1 in 1911, respectively. A combined scan of the heart and aorta had higher LARs, up to 1 in 114 for a 20-year-old woman. The highest organ LARs were for lung cancer and, in younger women, breast cancer.ConclusionsThese estimates derived from our simulation models suggest that use of 64-slice CTCA is associated with a nonnegligible LAR of cancer. This risk varies markedly and is considerably greater for women, younger patients, and for combined cardiac and aortic scans.

https://jamanetwork.com/journals/jama/articlepdf/208021/joc70075_317_323.pdf

Estimating Risk of Cancer Associated With Radiation Exposure From 64-Slice Computed Tomography Coronary Angiography

This continues the series of general reports on mortality in the cohort of atomic bomb survivors followed up by the Radiation Effects Research Foundation. This cohort includes 86,572 people with individual dose estimates, 60% of whom have doses of at least 5 mSv. We consider mortality for solid cancer and for noncancer diseases with 7 additional years of follow-up. There have been 9,335 deaths from solid cancer and 31,881 deaths from noncancer diseases during the 47-year follow-up. Of these, 19% of the solid cancer and 15% of the noncancer deaths occurred during the latest 7 years. We estimate that about 440 (5%) of the solid cancer deaths and 250 (0.8%) of the noncancer deaths were associated with the radiation exposure. The excess solid cancer risks appear to be linear in dose even for doses in the 0 to 150-mSv range. While excess rates for radiation-related cancers increase throughout the study period, a new finding is that relative risks decline with increasing attained age, as well as being highest for those exposed as children as noted previously. A useful representative value is that for those exposed at age 30 the solid cancer risk is elevated by 47% per sievert at age 70. There is no significant city difference in either the relative or absolute excess solid cancer risk. Site-specific analyses highlight the difficulties, and need for caution, in distinguishing between site-specific relative risks. These analyses also provide insight into the difficulties in interpretation and generalization of LSS estimates of age-at-exposure effects. The evidence for radiation effects on noncancer mortality remains strong, with risks elevated by about 14% per sievert during the last 30 years of follow-up. Statistically significant increases are seen for heart disease, stroke, digestive diseases, and respiratory diseases. The noncancer data are consistent with some non-linearity in the dose response owing to the substantial uncertainties in the data. There is no direct evidence of radiation effects for doses less than about 0.5 Sv. While there are no statistically significant variations in noncancer relative risks with age, age at exposure, or sex, the estimated effects are comparable to those seen for cancer. Lifetime risk summaries are used to examine uncertainties of the LSS noncancer disease findings.

https://bioone.org/journals/radiation-research/volume-160/issue-4/RR3049/Studies-of-Mortality-of-Atomic-Bomb-Survivors-Report-13/10.1667/RR3049.pdf

Studies of Mortality of Atomic Bomb Survivors. Report 13: Solid Cancer and Noncancer Disease Mortality: 1950–1997

Background. Ataxia—telangiectasia is an autosomal recessive syndrome in which cancers develop in affected homozygotes at a rate approximately 100 times higher than in unaffected age—matched subjects. Retrospective studies have shown that persons heterozygous for the ataxia—telangiectasia gene, who make up about 1 percent of the general population, also have an excess risk of cancer, particularly breast cancer in women. Patients with ataxia—telangiectasia and cells derived from homozygotes and heterozygotes are unusually sensitive to ionizing radiation. Methods. Cancer incidence and mortality, mortality from ischemic heart disease, and mortality from all causes were compared prospectively for a mean of 6.4 years in 1599 adult blood relatives of patients with ataxia—telangiectasia and 821 of their spouses, who served as controls, in 161 families affected by ataxia—telangiectasia. In a case–control substudy, we compared documented occupational and fluoroscopic diagnostic exposures to radiation in th...

https://www.nejm.org/doi/pdf/10.1056/NEJM199112263252602

Incidence of cancer in 161 families affected by ataxia-telangiectasia.

Ascertainment of breast cancer incidence among the cohort of the RERF Life Span Study extended sample identified 574 breast cancers among 564 cases diagnosed during 1950-1980 of which 412 cancers were reviewed microscopically. There were no dose-dependent differences with respect to diagnostic certainty or histological type. As in previous studies, the dose response appeared to be roughly linear and did not differ between the two cities. The most remarkable new finding was the emergence of a radiation-related excess among women under 10 years of age at exposure. The risk of radiogenic breast cancer appears to decrease with increasing age at exposure, whether expressed in relative or absolute terms. These results suggest that exposure of female breast tissue to ionizing radiation at any time during the first four decades of life, even during the premature stage, can cause breast cancer later in life, and that the length of time that tumor promoters such as endogenous hormones operate following exposure has an important influence on the development of radiation-induced breast cancer. An unresolved question is whether breast cancer risk is increased by radiation exposure at ages older than 40.

Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1980.

An incidence survey among atomic bomb survivors identified 807 breast cancer cases, and 20 second breast cancers. As in earlier surveys of the Life Span Study population, a strongly linear radiation dose response was found, with the highest dose-specific excess relative risk (ERR) among survivors under 20 years old at the time of the bombings. Sixty-eight of the cases were under 10 years old at exposure, strengthening earlier reports of a marked excess risk associated with exposure during infancy and childhood. A much lower, but marginally significant, dose response was seen among women exposed at 40 years and older. It was not possible, however, to discriminate statistically between age at exposure and age at observation for risk as the more important determinant of ERR per unit dose. A 13-fold ERR at 1 Sv was found for breast cancer occurring before age 35, compared to a 2-fold excess after age 35, among survivors exposed before age 20. This a posteriori finding, based on 27 exposed, known-dose, early-onset cases, suggests the possible existence of a susceptible genetic subgroup. Further studies, involving family histories of cancer and investigations at the molecular level, are suggested to determine whether such a subgroup exists.

Incidence of female breast cancer among atomic bomb survivors, 1950-1985

For 1950-74, 360 cases of malignant breast tumors were identified among the 63,000 females of the Radiation Effects Research Foundation's (Hiroshima and Nagasaki) Extended Life-Span Study sample of survivors of the 1945 atomic bombings of Hiroshima and Nagasaki; 288 of these females were residing in one of these two cities at the time of bombing (ATB). Two-thirds of all cases were classified as breast cancers on the basis of microscopic review of slides, and 108 cases received an estimated breast tissue dose of at least 10 rads. The number of cases of radiogenic breast cancer could be well estimated by a linear function of radiation dose for tissue doses below 200 rads. Excess risk estimates, based on this function, for women 10-19, 20-29, 30-39, and 50 years old or older ATB were 7.3, 4.2, 2.6, and 4.7 cases per million women per year per rad, respectively. Women irradiated in their forties showed no dose effect. Among all women who received at least 10 rads, those irradiated before age 20 years will have experienced the highest rates of breast cancer throughout their lifetimes. Separate excess risk estimates for Hiroshima and Nagasaki did not differ significantly, which indicates that for radiogenic breast cancer the effects of neutrons (emitted only in the Hiroshima explosion) and gamma radiation were about equal. Radiation did not reduce the latency period for the development of breast cancer, which was at least 10 years. The distribution of histologic types of cancers did not vary significantly with radiation dose. The data suggested that irradiation prior to menarche conferred a greater risk than irradiation after menarche.

Malignant breast tumors among atomic bomb survivors, Hiroshima and Nagasaki, 1950-74.

Ultrastructural and morphometrical studies were conducted on vascular tissue from 205 human Japanese specimens ranging in age from 15 weeks’ gestation to 90 years. Comparison of aorta size with overall body length by allometry revealed that the aging aorta has growth and involution stages comparable to other organs, and that progressive increase in aortic diameter was the major involutional change. The cellular and extracellular components of the medial sections of thoracic and abdominal aorta, renal artery, and superior mesenteric artery were quantitated from electron micrographs and compared at different ages. It was found that the renal artery rapidly accumulated extracellular material with increasing age; in the aortic tissue, however, the peak occurrence of extracellular material occurred at pubescence. Ultrastructural studies revealed a general tendency of aging medial smooth muscle cells to transform from a smooth, rounded morphology to become irregularly shaped.

Morphometrical analysis of the aging process in human arteries and aorta.

Three hundred and sixty cases of breast cancer were collected from among the 63,000 female members of the Radiation Effect Research Foundation (RERF) extended Life Span Study sample which includes atomic bomb exposed women and controls of Hiroshima and Nagasaki. The relationship of these breast cancer cases to A‐bomb radiation was sought, and in studying of 5‐year survival, the following conclusions were obtained concerning its relationship to histopathological findings. The prognosis of the 50+ rad high dose group is the best, followed by the nonexposed group and the low dose group. The apparently better survival may be due to the fact that this group is heavily weighted in favor of those who were younger at the time of the bomb (ATB). There is no specificity of the histologic type of breast cancer in the survivors by dose. Nor is any significant difference observed in the distribution of tumor size and histological grade, though the survival rates of this series are worse than those of usual Japanese women with breast cancer. Cellular reaction is significantly marked in the stroma of carcinoma tissue in the high dose group. Immune reaction is considered to be strong in the affected site of breast cancer in the high dose group and this can be regarded as a finding suggestive of good prognosis. Further extended studies are therefore warrented.

Issei Nishimori

Papers

Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1980.

Incidence of female breast cancer among atomic bomb survivors, 1950-1985

Malignant breast tumors among atomic bomb survivors, Hiroshima and Nagasaki, 1950-74.

Morphometrical analysis of the aging process in human arteries and aorta.

Breast cancer among atomic bomb survivors