RESUMEN
In this article we review the history of key epidemiological studies of populations exposed to ionizing radiation. We highlight historical and recent findings regarding radiation-associated risks for incidence and mortality of cancer and non-cancer outcomes with emphasis on study design and methods of exposure assessment and dose estimation along with brief consideration of sources of bias for a few of the more important studies. We examine the findings from the epidemiological studies of the Japanese atomic bomb survivors, persons exposed to radiation for diagnostic or therapeutic purposes, those exposed to environmental sources including Chornobyl and other reactor accidents, and occupationally exposed cohorts. We also summarize results of pooled studies. These summaries are necessarily brief, but we provide references to more detailed information. We discuss possible future directions of study, to include assessment of susceptible populations, and possible new populations, data sources, study designs and methods of analysis.
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Neoplasias Inducidas por Radiación , Exposición a la Radiación , Radiación Ionizante , Humanos , Exposición a la Radiación/efectos adversos , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/etiología , Historia del Siglo XX , Estudios Epidemiológicos , Historia del Siglo XXI , Exposición ProfesionalRESUMEN
Rare cancers collectively account for a significant proportion of the overall cancer burden in Japan. We aimed to describe and examine the incidence of each rare cancer and the temporal changes using the internationally agreed rare cancer classification. Cancer cases registered in regional population-based cancer registries from 2011 to 2015 and the National Cancer Registry (NCR) from 2016 to 2018 were classified into 18 families, 68 Tier-1 cancer groupings, and 216 single cancer entities based on the RARECAREnet list. Crude incidence rates and age-standardized incidence rates (ASR) were calculated for Tier-1 and Tier-2 cancers. The annual percent change and the 95% and 99% confidence limits for annual ASR for each of the 68 Tier-1 cancers were estimated using the log-linear regression of the weighted least squares method. The differences in ASRs between 2011 and 2018 were evaluated as an absolute change. A total of 5,640,879 cases were classified into Tier-1 and Tier-2 cancers. The ASRs of 18 out of 52 Tier-1 cancers in the rare cancer families increased, whereas the ASR for epithelial tumors of gallbladder decreased. The ASRs of 6 out of the 16 Tier-1 cancers in the common cancer families increased, whereas those of epithelial tumors of stomach and liver decreased. There was no significant change in the incidence of the other 40 Tier-1 cancers. The incidence of several cancers increased due to the dissemination of diagnostic concepts, improved diagnostic techniques, changes in coding practice, and the initiation of the NCR.
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Neoplasias , Sistema de Registros , Humanos , Japón/epidemiología , Incidencia , Neoplasias/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Enfermedades Raras/epidemiología , Lactante , Preescolar , Niño , Adulto Joven , Adolescente , Recién Nacido , Anciano de 80 o más AñosRESUMEN
The numbers of naive T cells that react to novel pathogens not yet encountered by an immune system, decrease during aging, mainly due to age-associated involution of the thymus. CD45RA+ naive CD4 T cells consist of heterogeneous populations, including highly CXCR3-expressing cells that appear during the homeostatic proliferation of naive T cells and exhibit enhanced type-1 inflammatory phenotypes. Based on previous evidence of radiation-associated reductions in thymic function and peripheral blood naive CD4 T cells, we hypothesized that the homeostatic proliferation of naive CD4 T cells compensates for deficits in peripheral T-cell populations after radiation injury, which may increase the proportion of CXCR3high cells in naive CD4 T cells and enhance inflammation. The statistical models employed in this study revealed positive associations between the number of CXCR3high naive CD4 T cells and age as well as radiation dose among 580 Hiroshima atomic bomb survivors. In addition, the CXCR3high cells in these survivors increased not only with the levels of homeostatic cytokines, IL6 and IL7, but also with those of inflammatory indicators, CXCL10 and CRP. These results suggest that thymic T-cell production deficiency due to radiation and aging results in enhanced homeostatic proliferation that drives the appearance of CXCR3high naive CD4 T cells poised for an inflammatory response. Molecular mechanisms and clinical relevance of increasing CXCR3high cells in naive CD4 T populations should be further investigated in the context of inflammatory disease development long after radiation exposure.
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Linfocitos T CD4-Positivos , Síndromes de Inmunodeficiencia , Exposición a la Radiación , Timo/anomalías , Humanos , Receptores de Quimiocina , Supervivientes a la Bomba Atómica , Envejecimiento , Receptores CXCR3RESUMEN
Advances in diagnostic techniques and treatment modalities have impacted head and neck cancer (HNC) prognosis, but their effects on subsite-specific prognosis remain unclear. This study aimed to assess subsite-specific trends in mid- and long-term survival for HNC patients diagnosed from 1993 to 2011 using data from population-based cancer registries in Japan. We estimated the net survival (NS) for HNC by subsite using data from 13 prefectural population-based cancer registries in Japan. Changes in survival over time were assessed by multivariate excess hazard model of mortality. In total, 68,312 HNC patients were included in this analysis. We observed an overall improvement in 5-year NS for HNC patients in Japan. However, survival varied among subsites of HNC, with some, such as naso-, oro- and hypopharyngeal cancers, showing significant improvement in both 5- and 10-year NS, whereas others such as laryngeal cancer showed only a slight improvement in 5-year NS and no significant change in 10-year NS after adjustment for age, sex and stage. In conclusion, the study provides insights into changing HNC survival by site at the population level in Japan. Although advances in diagnostic techniques and treatment modalities have improved survival, these improvements are not shared equally among subsites.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Laríngeas , Humanos , Japón/epidemiología , Neoplasias de Cabeza y Cuello/epidemiología , Neoplasias de Cabeza y Cuello/terapia , PronósticoRESUMEN
Cancer in children, adolescents, and young adults (AYAs) although rare, is the leading disease-specific cause of death in Japan. This study aims to investigate cancer incidence and type of treatment hospital among children and AYAs in Japan. Cancer incidence data (2016-2018) for those aged 0-39 years were obtained from the Japanese population-based National Cancer Registry. Cancer types were classified according to the 2017 update of the International Classification of Childhood Cancer (Third Edition), and AYA Site Recode 2020 Revision. Cases were also categorized into three groups: those treated at core hospitals for pediatric cancer treatment (pediatric cancer hospitals [PCHs]), those treated at designated cancer care hospitals, and those treated at nondesignated hospitals. The age-standardized incidence rate was 166.6 (per million-person years) for children (age 0-14 years) and 579.0 for AYAs (age 15-39 years) (including all cancers and benign or uncertain-behavior central nervous system [CNS] tumors). The type of cancer varied with age: hematological malignancies, blastomas, and CNS tumors were common in children under 10 years, malignant bone tumors and soft tissue sarcomas were relatively common in teenagers, and in young adults over 20 years, carcinomas in thyroid, testis, gastrointestinal, female cervix, and breast were common. The proportion of cases treated at PCHs ranged from 20% to 30% for children, 10% or less for AYAs, and differed according to age group and cancer type. Based on this information, the optimal system of cancer care should be discussed.
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Neoplasias Óseas , Neoplasias del Sistema Nervioso Central , Neoplasias , Masculino , Niño , Humanos , Adolescente , Femenino , Adulto Joven , Incidencia , Japón/epidemiología , Sistema de Registros , Neoplasias/epidemiología , Neoplasias/terapia , Neoplasias del Sistema Nervioso Central/patologíaRESUMEN
Following our previous report on the radiation dose-response for prostate cancer incidence rates in the Life Span Study (LSS) cohort of atomic bomb survivors, we reevaluated the radiation-related risk adjusting for differences in baseline cancer incidence rates among three subsets of the LSS cohort defined by the timing of their first participation in biennial health examinations offered to the Adult Health Study (AHS) sub-cohort members and prostate-specific-antigen (PSA) testing status for AHS participants: 1. non-AHS participants, 2. AHS participants before receiving PSA test, and 3. AHS participants after receiving PSA test. We found a 2.9-fold increase in the baseline incidence rates among AHS participants after receiving PSA test. After adjusting for the PSA-testing-status effects on the baseline rates the estimated excess relative risk (ERR) per Gy was 0.54 (95% CI: 0.15, 1.05), which was almost identical to the previously reported unadjusted ERR estimate (0.57, 95% CI: 0.21, 1.00). The current results confirmed that, while the PSA testing among AHS participants increased the baseline incidence rates, it did not impact the radiation risk estimate, strengthening the previously reported dose-response relationship for prostate cancer incidence in the LSS. As the use of PSA tests continue in screening and medical settings, analyses of possible effects of PSA testing should be an important aspect of future epidemiological studies of the association between radiation exposure and prostate cancer.
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Neoplasias Inducidas por Radiación , Neoplasias de la Próstata , Adulto , Masculino , Humanos , Incidencia , Antígeno Prostático Específico , Supervivientes a la Bomba Atómica , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/etiología , Sobrevivientes , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/etiología , Japón/epidemiologíaRESUMEN
Herein, we describe a highly potent gravitropic bending inhibitor with no concomitant growth inhibition. Previously, we reported that (2Z,4E)-5-phenylpenta-2,4-dienoic acid (ku-76) selectively inhibits root gravitropic bending of lettuce radicles at 5 µM. Based on the structure-activity relationship study of ku-76 as a lead compound, we designed and synthesized various C4-substituted analogs of ku-76. Among the analogs, 4-phenylethynyl analog exhibited the highest potency for gravitropic bending inhibition, which was effective at only 0.01 µM. Remarkably, 4-phenylethynyl analog is much more potent than the known inhibitor, NPA. Substitution in the para position on the aromatic ring of 4-phenylethynyl group was tolerated without diminished activity. In addition, evaluation using Arabidopsis indicated that 4-phenylethynyl analog inhibits gravitropism by affecting auxin distribution in the root tips. Based on the effects on Arabidopsis phenotypes, 4-phenylethynyl analog may be a novel inhibitor that differs in action from the previously reported auxin transport inhibitors.
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Proteínas de Arabidopsis , Arabidopsis , Gravitropismo/fisiología , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Relación Estructura-Actividad , Ácidos Indolacéticos/farmacología , Raíces de Plantas/metabolismoRESUMEN
BACKGROUND: Epidemiological characteristics of many types of rare cancers are limited especially in Asia. Therefore, this study aimed to describe the burden and changing time trends of rare cancers in Hiroshima, Japan. METHODS: The internationally agreed RARECAREnet list of rare cancers was used to identify patients diagnosed with cancers from 2005 to 2015 who were registered in the Hiroshima Prefecture Cancer Registry. Quality indicators specific to rare cancers were assessed by cancer grouping. Crude incidence rates (IRs) and age-standardized rates (ASRs) were calculated for 216 single cancers (rare and common) included in the list. A joinpoint regression was used to analyze age distribution and time trends in the ASRs for 12 internationally agreed rare cancer families. Quality indicators, ASRs, and IRs in Japan were identified to examine IR differences and the effects on data accuracy. RESULTS: The 231,328 cases were used to calculate the IRs of each cancer. Epithelial tumors in rare families increased with age, but nonepithelial tumors occurred at any age. The proportion of rare cancer families to total cancers was stable. The time trend for families of head and neck cancers (annual percent change and 95 % confidence interval: 2.4 %; 1.2-3.7 %), neuroendocrine tumors (6.6 %; 5.1-8.1 %), and hematological cancers (4.3 %; 3.2-5.5 %) markedly increased. CONCLUSION: The ASRs of several rare cancers increased because of increased knowledge of these diseases, improved diagnostic techniques, and aggressive diagnoses.
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Neoplasias de Cabeza y Cuello , Humanos , Distribución por Edad , Japón/epidemiología , Incidencia , Sistema de RegistrosRESUMEN
BACKGROUND: Comparison of the estimated effect of atomic bomb radiation exposure on solid cancer incidence and solid cancer mortality in the RERF Life Span Study (LSS) reveals a difference in the magnitude and shape of the excess relative risk dose response. A possible contributing factor to this difference is pre-diagnosis radiation effect on post-diagnosis survival. Pre-diagnosis radiation exposure theoretically could influence post-diagnosis survival by affecting the genetic makeup and possibly aggressiveness of cancer, or by compromising tolerance for aggressive treatment for cancer. METHODS: We analyze the radiation effect on post-diagnosis survival in 20,463 LSS subjects diagnosed with first-primary solid cancer between 1958 and 2009 with particular attention to whether death was caused by the first-primary cancer, other cancer, or non-cancer diseases. RESULTS: From multivariable Cox regression analysis of cause-specific survival, the excess hazard at 1 Gy (EH1Gy) for death from the first primary cancer was not significantly different from zero - p = 0.23, EH1Gy = 0.038 (95 % CI: -0.023, 0.104). Death from other cancer and death from non-cancer diseases both were significantly associated with radiation dose: other cancer EH1Gy = 0.38 (95 % CI: 0.24, 0.53); non-cancer EH1Gy = 0.24 (95 % CI: 0.13, 0.36), both p < 0.001. CONCLUSION: There is no detectable large effect of pre-diagnosis radiation exposure on post-diagnosis death from the first primary cancer in A-bomb survivors. IMPACT: A direct effect of pre-diagnosis radiation exposure on cancer prognosis is ruled out as an explanation for the difference in incidence and mortality dose response in A-bomb survivors.
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Neoplasias Inducidas por Radiación , Exposición a la Radiación , Humanos , Supervivientes a la Bomba Atómica , Neoplasias Inducidas por Radiación/etiología , Riesgo , Incidencia , Japón/epidemiologíaRESUMEN
BACKGROUND: National life table is commonly used for estimating cancer net survival. However, the national life table does not reflect condition of people in local area accurately, because there are disparities in cancer mortality rates among the local area in many cases. We investigated magnitude of difference in cancer net survival using the local area in Japan and Japanese life tables. METHODS: We analyzed data from 32,942 cancer patients diagnosed between 2010 and 2012 in Aomori prefecture, Japan. Expected survival rates in Aomori (ESA) and Japan (ESJ) were estimated based on the life table of each area. Five-year net survival rates using ESA and the ESJ were estimated using the Pohar-Perme method. RESULTS: The difference between net survival rates using the ESA (NSA) and the ESJ (NSJ) were larger than in men (0.3ï¼3.0%) than in women (0.1ï¼0.8%). The largest difference in the net survival rate was observed in prostate cancer patients, because the difference in the expected survival in oldest old men was remarkable. CONCLUSION: Two factors affected the difference in the net survival rates resulting from the sensitivity analysis. The difference was larger (1) among older patients or (2) with a longer observation period (person-years).
RESUMEN
One of the principal uncertainties when estimating population risk of late effects from epidemiological data is that few radiation-exposed cohorts have been followed up to extinction. Therefore, the relative risk model has often been used to estimate radiation-associated risk and to extrapolate risk to the end of life. Epidemiological studies provide evidence that children are generally at higher risk of cancer induction than adults for a given radiation dose. However, the strength of evidence varies by cancer site and questions remain about site-specific age at exposure patterns. For solid cancers, there is a large body of evidence that excess relative risk (ERR) diminishes with increasing age at exposure. This pattern of risk is observed in the Life Span Study (LSS) as well as in other radiation-exposed populations for overall solid cancer incidence and mortality and for most site-specific solid cancers. However, there are some disparities by endpoint in the degree of variation of ERR with exposure age, with some sites (e.g., colon, lung) in the LSS incidence data showing no variation, or even increasing ERR with increasing age at exposure. The pattern of variation of excess absolute risk (EAR) with age at exposure is often similar, with EAR for solid cancers or solid cancer mortality decreasing with increasing age at exposure in the LSS. We shall review the human data from the Japanese LSS cohort, and a variety of other epidemiological data sets, including a review of types of medical diagnostic exposures, also some radiobiological animal data, all bearing on the issue of variations of radiation late-effects risk with age at exposure and with attained age. The paper includes a summary of several oral presentations given in a Symposium on "Age effects on radiation response" as part of the 67th Annual Meeting of the Radiation Research Society, held virtually on 3-6 October 2021.
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A previous study of peripheral blood lymphocyte translocations around age 40 among atomic-bomb survivors exposed in utero revealed no overall association with radiation dose-despite a clear association between translocations and dose among their mothers-but the data suggested an increase at doses below 100 mGy with a definite peak. That analysis of the in utero-exposed survivors did not adjust for their subsequent smoking behavior, an established cause of chromosomal aberrations, or their subsequent exposures to medical irradiation, a potential mediator. In addition, atomic-bomb survivor radiation dose estimates have subsequently been updated and refined. We therefore re-estimated the dose response using the latest DS02R1 dose estimates and adjusting for smoking as well as for city and proximal-distal location at the time of exposure to the atomic bomb. Sex of the survivor, mother's age around the time of conception, and approximate trimester of gestation at the time of exposure were also considered as explanatory variables and modifiers. Precision of the estimated dose response was slightly lower due to greater variability near zero in the updated dose estimates, but there was little change in evidence of a low-dose increase and still no suggestion of an overall increase across the entire dose range. Adjustment for smoking behavior led to a decline in background number of translocations (the dose-response intercept), but smoking did not interact with dose overall (across the entire dose range). Adjustment for medical irradiation did not alter the association between dose and translocation frequency. Sex, mother's age, and trimester were not associated with number of translocations, nor did they interact with dose overall. Interactions with dose in the low-dose range could not be evaluated because of numerical instability.
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Neoplasias Inducidas por Radiación , Guerra Nuclear , Adulto , Aberraciones Cromosómicas , Relación Dosis-Respuesta en la Radiación , Humanos , Japón , Neoplasias Inducidas por Radiación/etiología , Dosis de Radiación , Fumar , SobrevivientesRESUMEN
We examined the mortality risks among 2463 individuals who were exposed in utero to atomic bomb radiation in Hiroshima or Nagasaki in August 1945 and were followed from October 1950 through 2012. Individual estimates of mother's weighted absorbed uterine dose (DS02R1) were used. Poisson regression method was used to estimate the radiation-associated excess relative risk per Gy (ERR/Gy) and 95% confidence intervals (CI) for cause-specific mortality. Head size, birth weight, and parents' survival status were evaluated as potential mediators of radiation effect. There were 339 deaths (216 males and 123 females) including deaths from solid cancer (n = 137), lymphohematopoietic cancer (n = 8), noncancer disease (n = 134), external cause (n = 56), and unknown cause (n = 4). Among males, the unadjusted ERR/Gy (95% CI) was increased for noncancer disease mortality (1.22, 0.10-3.14), but not for solid cancer mortality (- 0.18, < - 0.77-0.95); the unadjusted ERR/Gy for external cause mortality was not statistically significant (0.28, < - 0.60-2.36). Among females, the unadjusted ERRs/Gy were increased for solid cancer (2.24, 0.44-5.58), noncancer (2.86, 0.56-7.64), and external cause mortality (2.57, 0.20-9.19). The ERRs/Gy adjusted for potential mediators did not change appreciably for solid cancer mortality, but decreased notably for noncancer mortality (0.39, < - 0.43-1.91 for males; 1.48, - 0.046-4.55 for females) and external cause mortality (0.10, < - 0.57-1.96 for males; 1.38, < - 0.46-5.95 for females). In conclusion, antenatal radiation exposure is a consistent risk factor for increased solid cancer mortality among females, but not among males. The effect of exposure to atomic bomb radiation on noncancer disease and external cause mortality among individuals exposed in utero was mediated through small head size, low birth weight, and parental loss.
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Supervivientes a la Bomba Atómica/estadística & datos numéricos , Feto/efectos de la radiación , Exposición Materna/efectos adversos , Mortalidad , Neoplasias Inducidas por Radiación/mortalidad , Exposición a la Radiación/estadística & datos numéricos , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Relación Dosis-Respuesta en la Radiación , Femenino , Estudios de Seguimiento , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Embarazo/efectos de la radiación , Factores de RiesgoRESUMEN
BACKGROUND: Radiation exposure is an established risk factor for the development of several forms of cancer, including gastrointestinal cancers. However, few studies have investigated the relationship between prediagnostic radiation exposure and survival after cancer diagnosis. METHODS: Participants in the Life Span Study (LSS) of atomic bomb survivors who were diagnosed with a first primary invasive stomach, colon, or rectal cancer between 1958 and 2009 were followed for mortality during 1958-2014. Cox regression models were used to calculate HRs and 95% confidence intervals (CI) for associations of radiation dose from atomic bomb exposure with survival (cancer-specific and overall) after cancer diagnosis. Analyses were adjusted for city of primary exposure, sex, age at diagnosis, and year of diagnosis. RESULTS: We identified 7,728 eligible patients with cancer for analysis. We observed no statistically significant associations between radiation dose and cancer-specific survival among LSS participants with a gastrointestinal cancer. Higher radiation doses (≥1 Gy) were suggestively, but not significantly, associated with modestly poorer cancer-specific survival for colon cancer only (HR, 1.38; 95% CI, 0.90-2.12), and were associated with poorer overall survival regardless of cancer site. CONCLUSIONS: Although radiation exposure is associated with increased risk of gastrointestinal cancer incidence and mortality, study results are inconclusive about an association between prediagnostic radiation exposure and survival after gastrointestinal cancer diagnosis. IMPACT: Radiation exposure from the atomic bomb before gastrointestinal cancer diagnosis was not associated with cancer survival, but should be evaluated in relation to survival for other cancer types.
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Supervivientes a la Bomba Atómica , Neoplasias Gastrointestinales/etiología , Neoplasias Gastrointestinales/mortalidad , Neoplasias Inducidas por Radiación/mortalidad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Japón/epidemiología , Exposición a la RadiaciónRESUMEN
Epidemiological evidence for a radiation effect on prostate cancer risk has been inconsistent and largely indicative of no or little effect. Here we studied prostate cancer incidence among males of the Life Span Study cohort of atomic bomb survivors in a follow-up from 1958 to 2009, eleven years more than was previously reported. During this period there were 851 incident cases of prostate cancer among 41,544 male subjects, doubling the total number of cases in the cohort. More than 50% of the cases were diagnosed among those who were less than 20 years of age at the time of the bombings and who were at, or near, the ages of heightened prostate cancer risks during the last decade of follow-up. In analyses of the radiation dose response using Poisson regression methods, we used a baseline-rate model that allowed for calendar period effects corresponding to the emergence of prostate-specific antigen screening in the general population as well as effects of attained age and birth cohort. The model also allowed for markedly increased baseline rates among the Adult Health Study participants between 2005 and 2009, a period during which a prostate-specific antigen test was included in Adult Health Study biennial health examinations. We found a significant linear dose response with an estimated excess relative risk (ERR) per Gy of 0.57 (95% CI: 0.21, 1.00, P = 0.001). An estimated 40 of the observed cases were attributed to radiation exposure from the bombings. There was a suggestion of the ERR decreasing with increasing age at exposure (P = 0.09). We found no indication of effects of smoking, alcohol consumption and body mass index on the baseline risk of prostate cancer. The observed dose response strengthens the evidence of a radiation effect on the risk of prostate cancer incidence in the atomic bomb survivors.
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Supervivientes a la Bomba Atómica , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias de la Próstata/epidemiología , Exposición a la Radiación/efectos adversos , Adolescente , Adulto , Distribución por Edad , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Niño , Preescolar , Estudios de Cohortes , Humanos , Lactante , Japón/epidemiología , Longevidad , Masculino , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/patología , Guerra Nuclear , Armas Nucleares , Neoplasias de la Próstata/etiología , Neoplasias de la Próstata/patología , Factores de Riesgo , Adulto JovenRESUMEN
There is limited evidence concerning the association between radiation exposure and ovarian cancer. We evaluated radiation risk of ovarian cancer between 1958 and 2009 among 62,534 female atomic bomb survivors in the Life Span Study cohort, adding 11 years of follow-up from the previously reported study. Poisson regression methods were used to estimate excess relative risk per Gy (ERR/Gy) for total ovarian cancer and according to tumor type. We assessed the modifying effect of follow-up period and other factors on the radiation risk. We ascertained 288 first primary ovarian cancers including 77 type 1 epithelial cancers, 75 type 2 epithelial cancers, 66 epithelial cancers of undetermined type and 70 other cancers. Radiation dose was positively, although not significantly, associated with risk of total ovarian cancer [ERR/Gy = 0.30, 95% confidence interval (CI): -0.22 to 1.11]. There was a suggestion of heterogeneity in radiation effects (P = 0.08) for type 1 (ERR/Gy = -0.32, 95% CI: <-0.32 to 0.88) and type 2 cancers (ERR/Gy = 1.24, 95% CI: -0.08 to 4.16). There were no significant trends in the ERR with time since exposure or age at exposure. Further follow-up will help characterize more accurately the patterns of radiation risk for total ovarian cancer and its types.
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Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Ováricas/epidemiología , Exposición a la Radiación/efectos adversos , Adolescente , Adulto , Supervivientes a la Bomba Atómica , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Japón/epidemiología , Longevidad , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/patología , Armas Nucleares , Neoplasias Ováricas/patología , Factores de Riesgo , Adulto JovenRESUMEN
As part of the recent series of articles to create a comprehensive description of the radiation risks of solid cancer incidence after ionizing radiation exposure, based on the atomic bomb survivors' Life Span Study (LSS), this work focuses on the risks of urinary tract cancer (UTC) and kidney cancer. Analyses covered a 52-year period of follow-up, through 2009, among 105,444 eligible survivors who were alive and cancer free in 1958. This represents an additional 11 years of follow-up since the last comprehensive report, with a total of 3,079,502 person-years. We observed 790 UTC and 218 kidney cancer cases. Adjusted for smoking, there was a strong linear radiation dose response for UTC. The sex-averaged excess relative risk per 1 Gy (ERR/Gy) was 1.4 (95% confidence interval, CI: 0.82 to 2.1). Both males and females showed significantly increased ERRs/Gy with female point estimates at a factor of 3.4 (95% CI: 1.4 to 8.6) greater than male estimates. UTC radiation risks were largely unmodified by age at exposure or attained age. The attributable fraction of UTC to radiation exposure was approximately 18% while that attributed to smoking was 48%. Kidney cancer showed an increased ERR due to smoking (0.56 per 50 pack-years; 95% CI -0.007 to 1.6; P = 0.054), but we did not observe any strong associations of kidney cancer with radiation exposure, although sex-specific dose responses were found to be statistically different.
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Neoplasias Renales/epidemiología , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias Urológicas/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivientes a la Bomba Atómica , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Japón/epidemiología , Neoplasias Renales/etiología , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/patología , Armas Nucleares , Exposición a la Radiación/efectos adversos , Radiación Ionizante , Factores de Riesgo , Neoplasias de la Vejiga Urinaria/etiología , Neoplasias de la Vejiga Urinaria/patología , Neoplasias Urológicas/etiología , Neoplasias Urológicas/patología , Adulto JovenRESUMEN
Previously, we found (2Z,4E)-5-phenylpenta-2,4-dienoic acid (ku-76) to be a selective inhibitor of root gravitropic bending of lettuce radicles at 5 µM, with no concomitant growth inhibition, and revealed the structure-activity relationship in this inhibitory activity. The conformation of ku-76 is flexible owing to the open-chain structure of pentan-2,4-dienoic acid with freely rotating single bonds, and the (2Z)-alkene moiety may be isomerized by external factors. To develop more potent inhibitors and obtain insight into the target biomolecules, various analogues of ku-76, fixed through conformation and/or configuration, were synthesized and evaluated. Stereochemical fixation was effective in improving the potency of gravitropic bending inhibition. Finally, we found highly potent conformational and/or configurational analogues (ku-257, ku-294 and ku-308), that did not inhibit root growth. The inhibition of root curvature by these analogues was comparable to that of naptalam.
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Gravitropismo , Lactuca , Conformación Molecular , Raíces de Plantas , Relación Estructura-ActividadAsunto(s)
Supervivientes a la Bomba Atómica , Neoplasias , Humanos , Incidencia , Dosis de RadiaciónRESUMEN
Radiation exposure is among the few factors known to be associated with risk of central nervous system (CNS) tumors. However, the patterns of radiation risk by histological type, sex or age are unclear. We evaluated radiation risks of first primary glioma, meningioma, schwannoma, and other or not otherwise specified (other/NOS) tumors in the Life Span Study cohort of atomic bomb survivors. Cases diagnosed between 1958 and 2009 were ascertained through population-based cancer registries in Hiroshima and Nagasaki. To estimate excess relative risk per Gy (ERR/Gy), we fit rate models using Poisson regression methods. There were 285 CNS tumors (67 gliomas, 107 meningiomas, 49 schwannomas, and 64 other/NOS tumors) among 105,444 individuals with radiation dose estimates to the brain contributing 3.1 million person-years of observation. Based on a simple linear model without effect modification, ERR/Gy was 1.67 (95% confidence interval, CI: 0.12 to 5.26) for glioma, 1.82 (95% CI: 0.51 to 4.30) for meningioma, 1.45 (95% CI: - 0.01 to 4.97) for schwannoma, and 1.40 (95% CI: 0.61 to 2.57) for all CNS tumors as a group. For each tumor type, the dose-response was consistent with linearity and appeared to be stronger among males than among females, particularly for meningioma (P = 0.045). There was also evidence that the ERR/Gy for schwannoma decreased with attained age (P = 0.002). More than 60 years after the bombings, radiation risks for CNS tumors continue to be elevated. Further follow-up is necessary to characterize the lifetime risks of specific CNS tumors following radiation exposure.