Radiation and Risk of Liver, Biliary Tract, and Pancreatic Cancers among Atomic Bomb Survivors in Hiroshima and Nagasaki: 1958–2009

Sadakane, Atsuko; French, Benjamin; Brenner, Alina V.; Preston, Dale L.; Sugiyama, Hiromi; Grant, Eric J.; Sakata, Ritsu; Utada, Mai; Cahoon, Elizabeth K.; Mabuchi, Kiyóhiko; Ozasa, Kotaro

doi:10.1667/rr15341.1

Cited by 32 publications

(38 citation statements)

References 51 publications

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“…The major source of data on whole-body human exposures to gamma radiation is the Life Span Study (LSS) cohort that includes over 120,000 survivors of the atomic bombing in 1945 [3][4][5][6]. While these data have been a remarkable resource for epidemiological studies determining risks associated with acute exposures [5,[7][8][9][10][11][12][13], extrapolation of health risks to humans exposed intermittently to lower doses of radiation remains uncertain. Different mathematical modelling approaches have been used over the past 50 years to extrapolate health risks but they were met with variable enthusiasm from the scientific community [1,[14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Analyses of cancer incidence and other morbidities in gamma irradiated B6CF1 mice

2020

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With increasing medical radiation exposures, it is important to understand how different modes of delivery of ionizing radiation as well as total doses of exposure impact health outcomes. Our lab studied the risks associated with ionizing radiation by analyzing the Northwestern University Radiation Archive for animals (NURA). NURA contains detailed data from a series of 10 individual neutron and gamma irradiation experiments conducted on over 50,000 mice. Rigorous statistical testing on control mice from all Janus experiments enabled us to select studies that could be compared to one another and uncover unexpected differences among the controls as well as experimental animals. For controls, mice sham irradiated with 300 fractions died significantly earlier than those with fewer sham fractions and were excluded from the pooled dataset. Using the integrated dataset of gamma irradiated and control mice, we found that fractionation significantly decreased the death hazard for animals dying of lymphomas, tumors, non-tumors, and unknown causes. Gender differences in frequencies of causes of death were identified irrespective of irradiation and dose fractionation, with female mice being at a greater risk for all causes of death, except for lung tumors. Irradiated and control male mice were at a significantly greater risk for lung tumors, the opposite from observations noted in humans. Additionally, we discovered that lymphoma deaths can occur quickly after exposures to high doses of gamma rays. This study systematically cross-compared outcomes of different modes of fractionation evaluated across different Janus experiments and across a wide span of total doses. It demonstrates that protraction modulated survival and disease status differently based on the total dose, cause of death, and sex of an animal. This novel method for analyzing the Janus datasets will lead to insightful new mechanistic hypotheses and research in the fields of radiation biology and protection.

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Section: Introductionmentioning

confidence: 99%

Analyses of cancer incidence and other morbidities in gamma irradiated B6CF1 mice

2020

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“…13 The resultant data set consisted of 105,444 participants who experienced 1,885 first primary liver cancers (International Classification of Diseases for Oncology, 3rd edition: C22.0) over a total follow-up time of 3,078,205 person-years. 4 Analyses were based on a highly stratified table of case counts and accrued person-years. Within strata of city, sex, birth year and calendar year, person-years were adjusted for expected migration out of the Hiroshima and Nagasaki catchment areas, with estimated migration rates based on contacting data for a clinical subcohort (i.e., the Adult Health Study 1 ).…”

Section: Study Populationmentioning

confidence: 99%

“…The background rate was adjusted for city, in-city survivor vs. not-in-city resident, proximal (<3 km) vs. distal (≥3 km) location relative to the hypocenter, sex, birth cohort and attained age. 4,14 We did not adjust for lifestyle factors such as alcohol intake or Confirmed true-positive cases of primary liver cancer. 2 Potential true-positive cases of primary liver cancer.…”

Section: Excess Risk Modelsmentioning

confidence: 99%

“…1 Analyses of the Life Span Study data have consistently demonstrated that radiation exposure is associated with an increased risk of cancer mortality and incident solid cancer, including primary liver cancer. [2][3][4] Liver cancer is the sixth-most common cause of cancer death in Japan and the fourth-most common worldwide. 5 Because radiation risk estimates from the Life Span Study are used to inform policies for radiological protection in occupational, medical and public health settings, as well as for atomic bomb survivors' welfare, it is important to evaluate and improve the preciseness of those risk estimates.…”

Section: Introductionmentioning

confidence: 99%

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Misclassification of primary liver cancer in the Life Span Study of atomic bomb survivors

French

Sadakane

Cologne

et al. 2020

Intl Journal of Cancer

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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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“…While these authors could not find any radiation-induced effect for rectum cancer incidence, they did find a significant dose response for colon cancer incidence down to a few hundred mGy absorbed dose to the colon. Finally, a follow-up was done by Sadakane et al (2019) on cancer incidence in the liver, biliary tract and pancreas. A significantly elevated ERR per unit dose was found only for liver cancer, again with a largely linear dose response down to a few hundred mGy of absorbed dose to the liver.…”

Section: Organ Doses Of More Than 100 Mgy Do Matter-evidence From Thementioning

confidence: 99%

High CT doses return to the agenda

Rühm

Harrison

2019

Radiat Environ Biophys

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Modern medicine offers a variety of diagnostic methods and tools that include imaging techniques where patients are exposed to ionizing radiation such as X-radiography, CT scans, PET and others. In many countries, for example, the use of CT scans has continuously increased representing today an indispensable tool in X-ray diagnostics (UNSCEAR 2010). As a result, in particular in developed countries with health-care level I, even if averaged over the whole population of a certain country, medical exposures are largely responsible for exposure from manmade sources of ionizing radiation (UNSCEAR 2010). Recent studies suggest cumulative effective doses of more than 100 mSv from CT scans * W. Rühm

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Radiation and Risk of Liver, Biliary Tract, and Pancreatic Cancers among Atomic Bomb Survivors in Hiroshima and Nagasaki: 1958–2009

Cited by 32 publications

References 51 publications

Analyses of cancer incidence and other morbidities in gamma irradiated B6CF1 mice

Analyses of cancer incidence and other morbidities in gamma irradiated B6CF1 mice

Misclassification of primary liver cancer in the Life Span Study of atomic bomb survivors

High CT doses return to the agenda

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