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Kotaro Ozasa - One of the best experts on this subject based on the ideXlab platform.
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lifetime mortality risk from cancer and circulatory disease predicted from the japanese atomic bomb survivor life span Study data taking account of dose measurement error
Radiation Research, 2020Co-Authors: Mark P Little, Harry M Cullings, Richard Wakeford, David J Pawel, Munechika Misumi, Nobuyuki Hamada, Kotaro OzasaAbstract:Dosimetric measurement error is known to potentially bias the magnitude of the dose response, and can also affect the shape of dose response. In this report, generalized relative and absolute rate models are fitted to the latest Japanese atomic bomb survivor solid cancer, leukemia and circulatory disease mortality data (followed from 1950 through 2003), with the latest (DS02R1) dosimetry, using Bayesian techniques to adjust for errors in dose estimates and assessing other model uncertainties. Linear-quadratic models are fitted and used to assess lifetime mortality risks for contemporary UK, USA, French, Russian, Japanese and Chinese populations. For a test dose of 0.1 Gy absorbed dose weighted by neutron relative biological effectiveness, solid cancer, leukemia and circulatory disease mortality risks for a UK population using a generalized linear-quadratic relative rate model were estimated to be 3.88% Gy-1 [95% Bayesian credible interval (BCI): 1.17, 6.97], 0.35% Gy-1 (95% BCI: -0.03, 0.78) and 2.24% Gy-1 (95% BCI: -0.17, 13.76), respectively. Using a generalized absolute rate linear-quadratic model at 0.1 Gy, the lifetime risks for these three end points were estimated to be 3.56% Gy-1 (95% BCI: 0.54, 6.78), 0.41% Gy-1 (95% BCI: 0.01, 0.86) and 1.56% Gy-1 (95% BCI: -1.10, 7.21), respectively. There was substantial evidence of curvature for solid cancer (in particular, the group of solid cancers excluding lung, breast and stomach cancers) and leukemia, so that for solid cancer and leukemia, estimates of excess risk per unit dose were nearly doubled by increasing the dose from 0.01 to 1.0 Gy, with most of the increase occurring in the interval from 0.1 to 1.0 Gy. For circulatory disease, the dose-response curvature was inverse, so that risk per unit dose was nearly halved by going from 0.01 t o 1.0 Gy weighted absorbed dose, although there were substantial uncertainties. In general, there were higher radiation risks for females compared to males. This was true for solid cancer and circulatory disease overall, as well as for lung, breast, stomach and the group of other solid cancers, and was the case whether relative or absolute rate projection models were employed; however, for leukemia this pattern was reversed. Risk estimates varied somewhat between populations, with lower cancer risks in aggregate for China and Russia, but higher circulatory disease risks for Russia, particularly using the relative rate model. There was more pronounced variation for certain cancer sites and certain types of projection models, so that breast cancer risk was markedly lower in China and Japan using a relative rate model, but the opposite was the case for stomach cancer. There was less variation between countries using the absolute rate models for stomach cancer and breast cancer, but this was not the case for lung cancer and the group of other solid cancers, or for circulatory disease.
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Misclassification of primary liver cancer in the Life Span Study of atomic bomb survivors.
International journal of cancer, 2020Co-Authors: Benjamin French, Atsuko Sadakane, Kotaro Ozasa, Kiyohiko Mabuchi, John B. Cologne, Dale L. PrestonAbstract:Primary liver cancer is difficult to diagnose accurately at death, due to metastases from nearby organs and to concomitant diseases, such as chronic hepatitis and cirrhosis. Trends in diagnostic accuracy could affect radiation risk estimates for incident liver cancer by altering background rates or by impacting risk modification by sex and age. We quantified the potential impact of death-certificate inaccuracies on radiation risk estimates for liver cancer in the Life Span Study of atomic bomb survivors. True-positive and false-negative rates were obtained from a previous Study that compared death-certificate causes of death with those based on pathological review, from 1958 to 1987. We assumed various scenarios for misclassification rates after 1987. We obtained estimated true positives and estimated false negatives by stratified sampling from binomial distributions with probabilities given by the true-positive and false-negative rates, respectively. Poisson regression methods were applied to highly stratified person-year tables of corrected case counts and accrued person years. During the Study period (1958-2009), there were 1,885 cases of liver cancer, which included 383 death-certificate-only (DCO) cases; 1,283 cases with chronic liver disease as the underlying cause of death; and 150 DCO cases of pancreatic cancer among 105,444 Study participants. Across the range of scenarios considered, radiation risk estimates based on corrected case counts were attenuated, on average, by 13-30%. Our results indicated that radiation risk estimates for liver cancer were potentially sensitive to death-certificate inaccuracies. Additional data are needed to inform misclassification rates in recent years.
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Radiation risk of central nervous system tumors in the Life Span Study of atomic bomb survivors, 1958–2009
European Journal of Epidemiology, 2020Co-Authors: Alina V Brenner, Atsuko Sadakane, Ritsu Sakata, Dale L. Preston, Kiyohiko Mabuchi, Hiromi Sugiyama, Mai Utada, Elizabeth K Cahoon, Benjamin French, Kotaro OzasaAbstract: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.
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radiation risk of central nervous system tumors in the life span Study of atomic bomb survivors 1958 2009
European Journal of Epidemiology, 2020Co-Authors: Alina V Brenner, Atsuko Sadakane, Ritsu Sakata, Dale L. Preston, Kiyohiko Mabuchi, Hiromi Sugiyama, Mai Utada, Elizabeth K Cahoon, Benjamin French, Kotaro OzasaAbstract: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.
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effect of heterogeneity in background incidence on inference about the solid cancer radiation dose response in atomic bomb survivors
Radiation Research, 2019Co-Authors: John B. Cologne, Dale L. Preston, Kiyohiko Mabuchi, Hiromi Sugiyama, Harry M Cullings, Benjamin French, Jaeyoung Kim, Kotaro OzasaAbstract:A recent analysis of solid cancer incidence in the Life Span Study of atomic bomb survivors (Hiroshima and Nagasaki, Japan) found evidence of a nonlinear, upwardly curving radiation dose response among males but not among females. Further analysis of this new and unexpected finding was necessary. We used two approaches to investigate this finding. In one approach, we excluded individual cancer sites or groups of sites from all solid cancers. In the other approach, we used joint analysis to allow for heterogeneity in background-rate parameters across groups of cancers with dissimilar trends in background rates. Exclusion of a few sites led to the disappearance of curvature among males in the remaining collection of solid cancers; some of these influential sites have unique features in their background age-specific incidence that are not captured by a background-rate model fit to all solid cancers combined. Exclusion of a few sites also led to an appearance of curvature among females. Misspecification of background rates can cause bias in inference about the shape of the dose response, so heterogeneity of background rates might explain at least part of the all solid cancer dose-response difference in curvature between males and females. We conclude that analysis based on all solid cancers as a single outcome is not the optimal method to assess radiation risk for solid cancer in the Life Span Study; joint analysis with suitable choices of cancer groups might be preferable by allowing for background-rate heterogeneity across sites while providing greater power to assess radiation risk than analyses of individual sites.
Dale L. Preston - One of the best experts on this subject based on the ideXlab platform.
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Misclassification of primary liver cancer in the Life Span Study of atomic bomb survivors.
International journal of cancer, 2020Co-Authors: Benjamin French, Atsuko Sadakane, Kotaro Ozasa, Kiyohiko Mabuchi, John B. Cologne, Dale L. PrestonAbstract:Primary liver cancer is difficult to diagnose accurately at death, due to metastases from nearby organs and to concomitant diseases, such as chronic hepatitis and cirrhosis. Trends in diagnostic accuracy could affect radiation risk estimates for incident liver cancer by altering background rates or by impacting risk modification by sex and age. We quantified the potential impact of death-certificate inaccuracies on radiation risk estimates for liver cancer in the Life Span Study of atomic bomb survivors. True-positive and false-negative rates were obtained from a previous Study that compared death-certificate causes of death with those based on pathological review, from 1958 to 1987. We assumed various scenarios for misclassification rates after 1987. We obtained estimated true positives and estimated false negatives by stratified sampling from binomial distributions with probabilities given by the true-positive and false-negative rates, respectively. Poisson regression methods were applied to highly stratified person-year tables of corrected case counts and accrued person years. During the Study period (1958-2009), there were 1,885 cases of liver cancer, which included 383 death-certificate-only (DCO) cases; 1,283 cases with chronic liver disease as the underlying cause of death; and 150 DCO cases of pancreatic cancer among 105,444 Study participants. Across the range of scenarios considered, radiation risk estimates based on corrected case counts were attenuated, on average, by 13-30%. Our results indicated that radiation risk estimates for liver cancer were potentially sensitive to death-certificate inaccuracies. Additional data are needed to inform misclassification rates in recent years.
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Radiation risk of central nervous system tumors in the Life Span Study of atomic bomb survivors, 1958–2009
European Journal of Epidemiology, 2020Co-Authors: Alina V Brenner, Atsuko Sadakane, Ritsu Sakata, Dale L. Preston, Kiyohiko Mabuchi, Hiromi Sugiyama, Mai Utada, Elizabeth K Cahoon, Benjamin French, Kotaro OzasaAbstract: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.
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radiation risk of central nervous system tumors in the life span Study of atomic bomb survivors 1958 2009
European Journal of Epidemiology, 2020Co-Authors: Alina V Brenner, Atsuko Sadakane, Ritsu Sakata, Dale L. Preston, Kiyohiko Mabuchi, Hiromi Sugiyama, Mai Utada, Elizabeth K Cahoon, Benjamin French, Kotaro OzasaAbstract: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.
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effect of heterogeneity in background incidence on inference about the solid cancer radiation dose response in atomic bomb survivors
Radiation Research, 2019Co-Authors: John B. Cologne, Dale L. Preston, Kiyohiko Mabuchi, Hiromi Sugiyama, Harry M Cullings, Benjamin French, Jaeyoung Kim, Kotaro OzasaAbstract:A recent analysis of solid cancer incidence in the Life Span Study of atomic bomb survivors (Hiroshima and Nagasaki, Japan) found evidence of a nonlinear, upwardly curving radiation dose response among males but not among females. Further analysis of this new and unexpected finding was necessary. We used two approaches to investigate this finding. In one approach, we excluded individual cancer sites or groups of sites from all solid cancers. In the other approach, we used joint analysis to allow for heterogeneity in background-rate parameters across groups of cancers with dissimilar trends in background rates. Exclusion of a few sites led to the disappearance of curvature among males in the remaining collection of solid cancers; some of these influential sites have unique features in their background age-specific incidence that are not captured by a background-rate model fit to all solid cancers combined. Exclusion of a few sites also led to an appearance of curvature among females. Misspecification of background rates can cause bias in inference about the shape of the dose response, so heterogeneity of background rates might explain at least part of the all solid cancer dose-response difference in curvature between males and females. We conclude that analysis based on all solid cancers as a single outcome is not the optimal method to assess radiation risk for solid cancer in the Life Span Study; joint analysis with suitable choices of cancer groups might be preferable by allowing for background-rate heterogeneity across sites while providing greater power to assess radiation risk than analyses of individual sites.
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Radiation-Related Risk of Cancers of the Upper Digestive Tract among Japanese Atomic Bomb Survivors
Radiation research, 2019Co-Authors: Ritsu Sakata, Atsuko Sadakane, Eric J. Grant, Dale L. Preston, Hiromi Sugiyama, Alina V Brenner, Mai Utada, Benjamin French, Preetha Rajaraman, Elizabeth K CahoonAbstract:As a follow-up to the comprehensive work on solid cancer incidence in the Life Span Study (LSS) cohort of atomic bomb survivors between 1958 and 1998, we report here on updated radiation risk estim...
Kiyohiko Mabuchi - One of the best experts on this subject based on the ideXlab platform.
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Misclassification of primary liver cancer in the Life Span Study of atomic bomb survivors.
International journal of cancer, 2020Co-Authors: Benjamin French, Atsuko Sadakane, Kotaro Ozasa, Kiyohiko Mabuchi, John B. Cologne, Dale L. PrestonAbstract:Primary liver cancer is difficult to diagnose accurately at death, due to metastases from nearby organs and to concomitant diseases, such as chronic hepatitis and cirrhosis. Trends in diagnostic accuracy could affect radiation risk estimates for incident liver cancer by altering background rates or by impacting risk modification by sex and age. We quantified the potential impact of death-certificate inaccuracies on radiation risk estimates for liver cancer in the Life Span Study of atomic bomb survivors. True-positive and false-negative rates were obtained from a previous Study that compared death-certificate causes of death with those based on pathological review, from 1958 to 1987. We assumed various scenarios for misclassification rates after 1987. We obtained estimated true positives and estimated false negatives by stratified sampling from binomial distributions with probabilities given by the true-positive and false-negative rates, respectively. Poisson regression methods were applied to highly stratified person-year tables of corrected case counts and accrued person years. During the Study period (1958-2009), there were 1,885 cases of liver cancer, which included 383 death-certificate-only (DCO) cases; 1,283 cases with chronic liver disease as the underlying cause of death; and 150 DCO cases of pancreatic cancer among 105,444 Study participants. Across the range of scenarios considered, radiation risk estimates based on corrected case counts were attenuated, on average, by 13-30%. Our results indicated that radiation risk estimates for liver cancer were potentially sensitive to death-certificate inaccuracies. Additional data are needed to inform misclassification rates in recent years.
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Radiation risk of central nervous system tumors in the Life Span Study of atomic bomb survivors, 1958–2009
European Journal of Epidemiology, 2020Co-Authors: Alina V Brenner, Atsuko Sadakane, Ritsu Sakata, Dale L. Preston, Kiyohiko Mabuchi, Hiromi Sugiyama, Mai Utada, Elizabeth K Cahoon, Benjamin French, Kotaro OzasaAbstract: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.
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radiation risk of central nervous system tumors in the life span Study of atomic bomb survivors 1958 2009
European Journal of Epidemiology, 2020Co-Authors: Alina V Brenner, Atsuko Sadakane, Ritsu Sakata, Dale L. Preston, Kiyohiko Mabuchi, Hiromi Sugiyama, Mai Utada, Elizabeth K Cahoon, Benjamin French, Kotaro OzasaAbstract: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.
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effect of heterogeneity in background incidence on inference about the solid cancer radiation dose response in atomic bomb survivors
Radiation Research, 2019Co-Authors: John B. Cologne, Dale L. Preston, Kiyohiko Mabuchi, Hiromi Sugiyama, Harry M Cullings, Benjamin French, Jaeyoung Kim, Kotaro OzasaAbstract:A recent analysis of solid cancer incidence in the Life Span Study of atomic bomb survivors (Hiroshima and Nagasaki, Japan) found evidence of a nonlinear, upwardly curving radiation dose response among males but not among females. Further analysis of this new and unexpected finding was necessary. We used two approaches to investigate this finding. In one approach, we excluded individual cancer sites or groups of sites from all solid cancers. In the other approach, we used joint analysis to allow for heterogeneity in background-rate parameters across groups of cancers with dissimilar trends in background rates. Exclusion of a few sites led to the disappearance of curvature among males in the remaining collection of solid cancers; some of these influential sites have unique features in their background age-specific incidence that are not captured by a background-rate model fit to all solid cancers combined. Exclusion of a few sites also led to an appearance of curvature among females. Misspecification of background rates can cause bias in inference about the shape of the dose response, so heterogeneity of background rates might explain at least part of the all solid cancer dose-response difference in curvature between males and females. We conclude that analysis based on all solid cancers as a single outcome is not the optimal method to assess radiation risk for solid cancer in the Life Span Study; joint analysis with suitable choices of cancer groups might be preferable by allowing for background-rate heterogeneity across sites while providing greater power to assess radiation risk than analyses of individual sites.
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radiation and risk of liver biliary tract and pancreatic cancers among atomic bomb survivors in hiroshima and nagasaki 1958 2009
Radiation Research, 2019Co-Authors: Atsuko Sadakane, Ritsu Sakata, Eric J. Grant, Dale L. Preston, Hiromi Sugiyama, Alina V Brenner, Mai Utada, Elizabeth K Cahoon, Benjamin French, Kiyohiko MabuchiAbstract:The Life Span Study (LSS) of atomic bomb survivors has consistently demonstrated significant excess radiation-related risks of liver cancer since the first cancer incidence report. Here, we present...
Hiromi Sugiyama - One of the best experts on this subject based on the ideXlab platform.
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Gastrointestinal Cancer Survival and Radiation Exposure among Atomic Bomb Survivors: The Life Span Study.
Cancer epidemiology biomarkers & prevention : a publication of the American Association for Cancer Research cosponsored by the American Society of Pre, 2020Co-Authors: Brandie R Bockwoldt, Hiromi Sugiyama, Alina V Brenner, Benjamin French, Kevin Tsai, Parveen Bhatti, Kathleen F. Kerr, Eric R. Morenz, Amanda I. PhippsAbstract: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 pre-diagnostic 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 1958-2009 were followed for mortality during 1958-2014. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) 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 cancer patients 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 pre-diagnostic 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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radiation risk of central nervous system tumors in the life span Study of atomic bomb survivors 1958 2009
European Journal of Epidemiology, 2020Co-Authors: Alina V Brenner, Atsuko Sadakane, Ritsu Sakata, Dale L. Preston, Kiyohiko Mabuchi, Hiromi Sugiyama, Mai Utada, Elizabeth K Cahoon, Benjamin French, Kotaro OzasaAbstract: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.
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Radiation risk of central nervous system tumors in the Life Span Study of atomic bomb survivors, 1958–2009
European Journal of Epidemiology, 2020Co-Authors: Alina V Brenner, Atsuko Sadakane, Ritsu Sakata, Dale L. Preston, Kiyohiko Mabuchi, Hiromi Sugiyama, Mai Utada, Elizabeth K Cahoon, Benjamin French, Kotaro OzasaAbstract: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.
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effect of heterogeneity in background incidence on inference about the solid cancer radiation dose response in atomic bomb survivors
Radiation Research, 2019Co-Authors: John B. Cologne, Dale L. Preston, Kiyohiko Mabuchi, Hiromi Sugiyama, Harry M Cullings, Benjamin French, Jaeyoung Kim, Kotaro OzasaAbstract:A recent analysis of solid cancer incidence in the Life Span Study of atomic bomb survivors (Hiroshima and Nagasaki, Japan) found evidence of a nonlinear, upwardly curving radiation dose response among males but not among females. Further analysis of this new and unexpected finding was necessary. We used two approaches to investigate this finding. In one approach, we excluded individual cancer sites or groups of sites from all solid cancers. In the other approach, we used joint analysis to allow for heterogeneity in background-rate parameters across groups of cancers with dissimilar trends in background rates. Exclusion of a few sites led to the disappearance of curvature among males in the remaining collection of solid cancers; some of these influential sites have unique features in their background age-specific incidence that are not captured by a background-rate model fit to all solid cancers combined. Exclusion of a few sites also led to an appearance of curvature among females. Misspecification of background rates can cause bias in inference about the shape of the dose response, so heterogeneity of background rates might explain at least part of the all solid cancer dose-response difference in curvature between males and females. We conclude that analysis based on all solid cancers as a single outcome is not the optimal method to assess radiation risk for solid cancer in the Life Span Study; joint analysis with suitable choices of cancer groups might be preferable by allowing for background-rate heterogeneity across sites while providing greater power to assess radiation risk than analyses of individual sites.
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Radiation-Related Risk of Cancers of the Upper Digestive Tract among Japanese Atomic Bomb Survivors
Radiation research, 2019Co-Authors: Ritsu Sakata, Atsuko Sadakane, Eric J. Grant, Dale L. Preston, Hiromi Sugiyama, Alina V Brenner, Mai Utada, Benjamin French, Preetha Rajaraman, Elizabeth K CahoonAbstract:As a follow-up to the comprehensive work on solid cancer incidence in the Life Span Study (LSS) cohort of atomic bomb survivors between 1958 and 1998, we report here on updated radiation risk estim...
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japanese legacy cohorts the life span Study atomic bomb survivor cohort and survivors offspring
Journal of Epidemiology, 2018Co-Authors: Kotaro Ozasa, Eric J. Grant, Kazunori KodamaAbstract:Cohorts of atomic bomb survivors-including those exposed in utero-and children conceived after parental exposure were established to investigate late health effects of atomic bomb radiation and its transgenerational effects by the Atomic Bomb Casualty Commission (ABCC) in the 1950s. ABCC was reorganized to the Radiation Effects Research Foundation (RERF) in 1975, and all work has been continued at RERF. The Life Span Study, the cohort of survivors, consists of about 120,000 subjects and has been followed since 1950. Cohorts of in utero survivors and the survivors' children include about 3,600 and 77,000 subjects, respectively, and have been followed since 1945. Atomic bomb radiation dose was estimated for each subject based on location at the time of the bombing and shielding conditions from exposure, which were obtained through enormous efforts of investigators and cooperation of subjects. Outcomes include vital status, cause of death, and cancer incidence. In addition, sub-cohorts of these three cohorts were constructed to examine clinical features of late health effects, and the subjects have been invited to periodic health examinations at clinics of ABCC and RERF. They were also asked to donate biosamples for biomedical investigations. Epidemiological studies have observed increased radiation risks for malignant diseases among survivors, including those exposed in utero, and possible risks for some non-cancer diseases. In children of survivors, no increased risks due to parental exposure to radiation have been observed for malignancies or other diseases, but investigations are continuing, as these cohorts are still relatively young.
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Heart Disease Mortality in the Life Span Study, 1950–2008
Radiation research, 2017Co-Authors: Ikuno Takahashi, Kotaro Ozasa, Eric J. Grant, Yukiko Shimizu, John B. Cologne, Kazunori KodamaAbstract:Based on the findings from the Radiation Effects Research Foundation's studies of the cohort of Japanese atomic bomb survivors, it has been reported that total-body irradiation at 0.5–1.0 Gy could be responsible for increased rates of mortality from broad-based categories of cardiovascular disease (CVD), i.e., stroke and heart disease. However, CVD consists of various subtypes that have potentially different radiation dose responses, as well as subtype-specific risks that have not been fully evaluated. Potential problems with changes in the coding rules for the International Classification of Diseases (ICD) and the underlying causes and trends in CVD mortality in Japan also need to be considered. The goal of this Study was to clarify the radiation risk of subtype-specific heart disease over different time periods. Radiation dose response was examined for mortality from several heart disease subtypes in 86,600 members of the Life Span Study (LSS) cohort during 1950–2008. These subtypes included ischemic he...
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long term effects of radiation exposure on health
The Lancet, 2015Co-Authors: Kenji Kamiya, Kotaro Ozasa, Kazunori Kodama, Suminori Akiba, Ohstura Niwa, Noboru Takamura, Elena Karamfilova Zaharieva, Yuko Kimura, Richard WakefordAbstract:Summary Late-onset effects of exposure to ionising radiation on the human body have been identified by long-term, large-scale epidemiological studies. The cohort Study of Japanese survivors of the atomic bombings of Hiroshima and Nagasaki (the Life Span Study) is thought to be the most reliable source of information about these health effects because of the size of the cohort, the exposure of a general population of both sexes and all ages, and the wide range of individually assessed doses. For this reason, the Life Span Study has become fundamental to risk assessment in the radiation protection system of the International Commission on Radiological Protection and other authorities. Radiation exposure increases the risk of cancer throughout life, so continued follow-up of survivors is essential. Overall, survivors have a clear radiation-related excess risk of cancer, and people exposed as children have a higher risk of radiation-induced cancer than those exposed at older ages. At high doses, and possibly at low doses, radiation might increase the risk of cardiovascular disease and some other non-cancer diseases. Hereditary effects in the children of atomic bomb survivors have not been detected. The dose–response relation for cancer at low doses is assumed, for purposes of radiological protection, to be linear without a threshold, but has not been shown definitively. This outstanding issue is not only a problem when dealing appropriately with potential health effects of nuclear accidents, such as at Fukushima and Chernobyl, but is of growing concern in occupational and medical exposure. Therefore, the appropriate dose–response relation for effects of low doses of radiation needs to be established.
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a report from the 2013 international symposium the evaluation of the effects of low dose radiation exposure in the life span Study of atomic bomb survivors and other similar studies
Health Physics, 2015Co-Authors: Eric J. Grant, Kotaro Ozasa, John B. Cologne, Harry M Cullings, Kyoji Furukawa, Nobuhiko Ban, Berrington A De Gonzalez, Kunio Doi, T Imaoka, Kazunori KodamaAbstract:The RERF International Low-Dose Symposium was held on 5-6 December 2013 at the RERF campus in Hiroshima, Japan, to discuss the issues facing the Life Span Study (LSS) and other low-dose studies. Topics included the current status of low-dose risk detection, strategies for low-dose epidemiological and statistical research, methods to improve communication between epidemiologists and biologists, and the current status of radiological studies and tools. Key points made by the participants included the necessity of pooling materials over multiple studies to gain greater insight where data from single studies are insufficient; generating models that reflect epidemiological, statistical, and biological principles simultaneously; understanding confounders and effect modifiers in the current data; and taking into consideration less studied factors such as the impact of dose rate. It is the hope of all participants that this symposium be used as a trigger for further studies, especially those using pooled data, in order to reach a greater understanding of the health effects of low-dose radiation.
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radiation and smoking effects on lung cancer incidence by histological types among atomic bomb survivors
Radiation Research, 2012Co-Authors: Hiromi Egawa, Kotaro Ozasa, Dale L. Preston, Shoji Tokuoka, Sachiyo Funamoto, Akihiko Suyama, Kyoji Furukawa, Shuji Yonehara, Takeshi Matsuo, Kazunori KodamaAbstract:While the risk of lung cancer associated separately with smoking and radiation exposure has been widely reported, it is not clear how smoking and radiation together contribute to the risk of specific lung cancer histological types. With individual smoking histories and radiation dose estimates, we characterized the joint effects of radiation and smoking on type-specific lung cancer rates among the Life Span Study cohort of Japanese atomic bomb survivors. Among 105,404 cohort subjects followed between 1958 and 1999, 1,803 first primary lung cancer incident cases were diagnosed and classified by histological type. Poisson regression methods were used to estimate excess relative risks under several interaction models. Adenocarcinoma (636 cases), squamous-cell carcinoma (330) and small-cell carcinoma (194) made up 90% of the cases with known histology. Both smoking and radiation exposure significantly increased the risk of each major lung cancer histological type. Smoking-associated excess relative risks were...