Shinji Yoshinaga

Cancer incidence in the U.S. radiologic technologists health study, 1983–1998

Workers exposed to low doses of radiation can provide information regarding cancer risks that are of public concern. However, characterizing risk at low doses requires large populations and ideally should include a large proportion of women, both of which rarely are available.

Nonmelanoma skin cancer in relation to ionizing radiation exposure among U.S. radiologic technologists.

Ionizing radiation (IR) is an established cause of nonmelanoma skin cancer, but there is uncertainty about the risk associated with chronic occupational exposure to IR and how it is influenced by ultraviolet radiation (UVR) exposure. We studied 1,355 incident cases with basal cell carcinoma (BCC) and 270 with squamous cell carcinoma (SCC) of the skin in a cohort of 65,304 U.S. white radiologic technologists who responded to the baseline questionnaire survey in 1983–1989 and the follow‐up survey in 1994–1998. Coxs proportional‐hazards model was used to estimate relative risks of BCC and SCC associated with surrogate measures of occupational exposure to IR and residential UVR exposure during childhood and adulthood, adjusted for potential confounders including pigmentation characteristics. Relative risks of BCC, but not of SCC, were elevated among technologists who first worked during the 1950s (RR = 1.42; 95% CI = 1.12–1.80), 1940s (RR = 2.04; 95% CI = 1.44–2.88) and before 1940 (RR = 2.16; 95% CI = 1.14–4.09), when IR exposures were high, compared to those who first worked after 1960 (p for trend < 0.01). The effect of year first worked on BCC risk was not modified by UVR exposure, but was significantly stronger among individuals with lighter compared to darker eye and hair color (p = 0.013 and 0.027, respectively). This study provides some evidence that chronic occupational exposure to IR at low to moderate levels can increase the risk of BCC, and that this risk may be modified by pigmentation characteristics.

Meta-analysis of second cancer risk after radiotherapy among childhood cancer survivors.

Cancer risks among childhood cancer survivors following radiotherapy have not yet been well characterised in terms of radiation dose. A meta-analysis of studies on the excess relative risk per gray (ERR) of second cancer was conducted previously; unfortunately, the small number of eligible studies restricted quantitative evaluations. To solve this problem, a statistical method to calculate ERR estimates from other estimates was developed, and a meta-analysis was conducted again. The PubMed database was searched and 26 relevant studies were identified. ERR estimates were available in 15 studies, and for the other 11 studies, the regression-based model was used to calculate ERR estimates from other estimates. The overall ERR estimate was 0.40, which was much lower than that of atomic bomb survivors exposed as young children. Heterogeneity of the risk among studies was suggested, and a further study is needed to explore the heterogeneity among studies.

Risk of second malignant neoplasms among childhood cancer survivors treated with radiotherapy: meta-analysis of nine epidemiological studies.

In the light of notable advances made in childhood cancer therapies, an understanding of the late effects of treatment is important for continued medical care. We conducted a meta-analysis of studies on the excess relative risk (ERR) of second malignant neoplasm (SMN) among childhood cancer survivors treated with radiotherapy. Relevant studies were retrieved by searching the PubMed database, supplemented by hand-searching of reference lists of already retrieved papers. Nine studies were identified and overall ERR estimates were calculated using a fixed effects model and a random effects model. The overall ERR per Gy (absorbed dose of ionising radiation) estimates of radiotherapy by a fixed effect model and a random effects model were 0.50 [95% CI 0.20, 1.21] and 0.53 [95% CI 0.22, 1.31] respectively. Heterogeneity among studies was suggested by Cochrans Q statistic (Q = 40.4, d.f. = 8, P < 0.001). The estimate obtained using a random effects model was far smaller than the corresponding estimate of 1.7 [95% CI 1.1, 2.5] from the study on atomic bomb survivors exposed as young children, suggesting underestimation of ERR estimates among the nine studies compared with the estimates from the study of atomic bomb survivors. In view of the heterogeneity and underestimation in ERR estimates, more studies concerning the risk of SMN among childhood cancer survivors are still needed for further understanding of the carcinogenic effects of radiotherapy on children.

Research on potential radiation risks in areas with nuclear power plants in Japan: leukaemia and malignant lymphoma mortality between 1972 and 1997 in 100 selected municipalities.

The results of a geographical correlation study using Poisson regression analysis are reported for leukaemia and malignant lymphoma mortality between 1972 and 1997 in 100 selected Japanese municipalities with or without a nuclear power plant (NPP). The data did not support social concerns of an increased risk of malignant lymphoma in the vicinity of Japanese NPPs. However, some estimates of overall excess relative risk (ERR; relative risk minus one) were statistically significantly positive for leukaemia mortality in 20 NPP municipalities compared with mortality in the remaining 80 control areas, taking into account a minimum two-year latency following the start of commercial operation. One estimate was 0.228 (95% CI: 0.074-0.404) from a simple area adjustment using the mortality in all Japan as the external baseline rate. This superficial increase is not due to leukaemia among young people, aged less than 25 years at death. The ERR estimate for ages at death of 50-74 years was confounded to be positive for leukaemia and distorted to be negative for malignant lymphoma. For leukaemia, a positive ERR estimate was seen, especially for females and during specific periods. Confounding of the ERR estimate for two causes was also seen in some NPP areas including a high adult T-cell leukaemia (ATL) area. Temporal area variations associated with ATL misclassification and a temporal increasing trend of leukaemia mortality in the elderly caused the confounding effects. Our findings do not support the hypothesis of a leukaemogenic impact of NPPs in Japan.

Combined exposure to X-irradiation followed by N-ethyl-N-nitrosourea treatment alters the frequency and spectrum of Ikaros point mutations in murine T-cell lymphoma.

Ionizing radiation is a well-known carcinogen, but its potency may be influenced by other environmental carcinogens, which is of practical importance in the assessment of risk. Data are scarce, however, on the combined effect of radiation with other environmental carcinogens and the underlying mechanisms involved. We studied the mode and mechanism of the carcinogenic effect of radiation in combination with N-ethyl-N-nitrosourea (ENU) using doses approximately equal to the corresponding thresholds. B6C3F1 mice exposed to fractionated X-irradiation (Kaplans method) followed by ENU developed T-cell lymphomas in a dose-dependent manner. Radiation doses above an apparent threshold acted synergistically with ENU to promote lymphoma development, whereas radiation doses below that threshold antagonized lymphoma development. Ikaros, which regulates the commitment and differentiation of lymphoid lineage cells, is a critical tumor suppressor gene frequently altered in both human and mouse lymphomas and shows distinct mutation spectra between X-ray- and ENU-induced lymphomas. In the synergistically induced lymphomas, we observed a low frequency of LOH and an inordinate increase of Ikaros base substitutions characteristic of ENU-induced point mutations, G:C to A:T at non-CpG, A:T to G:C, G:C to T:A and A:T to T:A. This suggests that radiation doses above an apparent threshold activate the ENU mutagenic pathway. This is the first report on the carcinogenic mechanism elicited by combined exposure to carcinogens below and above threshold doses based on the mutation spectrum of the causative gene. These findings constitute a basis for assessing human cancer risk following exposure to multiple carcinogens.

Biological measures to minimize the risk of radiotherapy-associated second cancer: a research perspective

Abstract Purpose Second cancers are among the most serious sequelae for cancer survivors who receive radiotherapy. This article aims to review current knowledge regarding how the risk of radiotherapy-associated second cancer can be minimized by biological measures and to discuss relevant research needs. Results The risk of second cancer can be reduced not only by physical measures to decrease the radiation dose to normal tissues but also by biological means that interfere with the critical determinants of radiation-induced carcinogenesis. Requirements for such biological means include the targeting of tumor types relevant to radiotherapy-associated risk, concrete safety and efficacy evidence and feasibility and minimal invasiveness. Mechanistic insights into the process of radiation carcinogenesis provide rational approaches to minimize the risk. Five mechanism-based strategies are proposed herein based on the current state of knowledge. Epidemiological studies on the joint effects of radiation and lifestyle or other factors can provide evidence for factors that modify radiation-associated risks if deliberately controlled. Conclusions Mechanistic and epidemiological evidence indicates that it is possible to develop interventional measures to minimize the second cancer risk associated with radiotherapy. Research is needed regarding the critical determinants of radiation-induced carcinogenesis available for intervention and joint effects of radiation and controllable factors.

Nationwide survey on pediatric CT among children of public health and school nurses to examine a possibility for a follow-up study on radiation effects

A nationwide survey was conducted in Japan on paediatric CT among children of public health and school nurses to examine a possibility for a follow-up study on radiation effects. A survey questionnaire was sent out to 3173 public primary and junior high schools and 317 public health centres during October to December in 2009. According to the collected responses, 410 (16.2 %) children received the CT scans and the total number of CT scans was 585. Most of respondents expressed a high interest in radiation health effects and an intent to participate in the epidemiological study that will follow-up the health conditions of children. This study provides information to discuss the feasibility of the epidemiological study on health effects in children who received CT scans.

Methodological extensions of meta-analysis with excess relative risk estimates: application to risk of second malignant neoplasms among childhood cancer survivors treated with radiotherapy

Although radiotherapy is recognized as an established risk factor for second malignant neoplasms (SMNs), the dose response of SMNs following radiotherapy has not been well characterized. In our previous meta-analysis of the risks of SMNs occurring among children who have received radiotherapy, the small number of eligible studies precluded a detailed evaluation. Therefore, to increase the number of eligible studies, we developed a method of calculating excess relative risk (ERR) per Gy estimates from studies for which the relative risk estimates for several dose categories were available. Comparing the calculated ERR with that described in several original papers validated the proposed method. This enabled us to increase the number of studies, which we used to conduct a meta-analysis. The overall ERR per Gy estimate of radiotherapy over 26 relevant studies was 0.60 (95%CI: 0.30–1.20), which is smaller than the corresponding estimate for atomic bomb survivors exposed to radiation as young children (1.7; 95% CI: 1.1–2.5). A significant decrease in ERR per Gy with increase in age at exposure (0.85 times per annual increase) was observed in the meta-regression. Heterogeneity was suggested by Cochrans Q statistic (P < 0.001), which may be partly accounted for by age at exposure.

Effect of radon measurement methods on dose estimation

Different radon measurement methods were applied in the old and new buildings of the Turkish bath of Eger, Hungary, in order to elaborate a radon measurement protocol. Besides, measurements were also made concerning the radon and thoron short-lived decay products, gamma dose from external sources and water radon. The most accurate results for dose estimation were provided by the application of personal radon meters. Estimated annual effective doses from radon and its short-lived decay products in the old and new buildings, using 0.2 and 0.1 measured equilibrium factors, were 0.83 and 0.17 mSv, respectively. The effective dose from thoron short-lived decay products was only 5 % of these values. The respective external gamma radiation effective doses were 0.19 and 0.12 mSv y(-1). Effective dose from the consumption of tap water containing radon was 0.05 mSv y(-1), while in the case of spring water, it was 0.14 mSv y(-1).