Incidence of lymphoid neoplasms among atomic bomb survivors by histological subtype, 1950 to 1994.

Epidemiological data have provided limited and inconsistent evidence on the relationship between radiation exposure and lymphoid neoplasms. We classified 553 lymphoid neoplasm cases diagnosed between 1950 and 1994 in the Life Span Study cohort of atomic bomb survivors into World Health Organization subtypes. Mature B-cell neoplasms represented 58%, mature T-cell and natural killer (NK)-cell neoplasms 20%, precursor cell neoplasms 5%, and Hodgkin lymphoma (HL) 3%, with the remaining 15% classified as non-Hodgkin lymphoid (NHL) neoplasms or lymphoid neoplasms not otherwise specified. We used Poisson regression methods to assess the relationship between radiation exposure and the more common subtypes. As in earlier reports, a significant dose response for NHL neoplasms as a group was seen for males but not females. However, subtype analyses showed that radiation dose was strongly associated with increased precursor cell neoplasms rates, with an estimated excess relative risk per Gy of 16 (95% Confidence interval: 7.0, >533) at age 50. The current data based primarily of tissue-based diagnoses suggest that the association between radiation dose and lymphoid neoplasms as a group is largely driven by the radiation effect on precursor cell neoplasms while presenting no evidence of a radiation dose response for major categories of mature cell neoplasms, either B- or T-/NK-cell, or more specific disease entities (diffuse large B-cell lymphoma, plasma cell myeloma, adult T-cell leukemia/lymphoma) or HL.

Cigarette Smoking, Smoking Cessation, and Bladder Cancer Risk: A Pooled Analysis of 10 Cohort Studies in Japan.

BACKGROUND: Although cigarette smoking is an established risk factor for bladder cancer, assessment of smoking impact on bladder cancer in Asian populations has been hindered by few cohort studies conducted in Asian populations. Therefore, we investigated the risk of bladder cancer associated with smoking status, cumulative smoking intensity, and smoking cessation in Japan. METHODS: We analyzed data for 157,295 men and 183,202 women in 10 population-based cohort studies in Japan. The risk associated with smoking behaviors was estimated using Cox regression models within each study, and pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for the incidence of bladder cancer were calculated. RESULTS: During 4,729,073 person-years of follow-up, 936 men and 325 women developed bladder cancer. In men, former smokers (HR 1.47; 95% CI, 1.18-1.82) and current smokers (HR 1.96; 95% CI, 1.62-2.38) had higher risk than never smokers. In women, current smokers had higher risk than never smokers (HR 2.35; 95% CI, 1.67-3.32). HRs in men linearly increased with increasing pack-years. Risk decreased with increasing years of smoking cessation in men, with a significant dose-response trend. Former smokers with a duration of more than 10 years after smoking cessation had no significantly increased risk compared with never smokers (HR 1.26; 95% CI, 0.97-1.63). CONCLUSION: Data from a pooled analysis of 10 population-based cohort studies in Japan clearly show an association between cigarette smoking and bladder cancer risk. The risk of smokers may approximate that of never smokers following cessation for many years.

Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia.

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet  = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.

Alcohol intake and stomach cancer risk in Japan: A pooled analysis of six cohort studies.

The association between alcohol intake and stomach cancer risk remains controversial. We undertook a pooled analysis of data from six large-scale Japanese cohort studies with 256 478 participants on this topic. Alcohol intake as ethanol was estimated using a validated questionnaire. The participants were followed for incidence of stomach cancer. We calculated study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for stomach cancer according to alcohol intake using a Cox regression model. Summary HRs were estimated by pooling the study-specific HRs using a random-effects model. During 4 265 551 person-years of follow-up, 8586 stomach cancer cases were identified. In men, the multivariate-adjusted HRs (95% CIs) of stomach cancer were 1.00 (0.87-1.15) for occasional drinkers, and 1.00 (0.91-1.11) for <23 g/d, 1.09 (1.01-1.18) for 23 to <46 g/d, 1.18 (1.09-1.29) for 46 to <69 g/d, 1.21 (1.05-1.39) for 69 to <92 g/d, and 1.29 (1.11-1.51) for ≥92 g/d ethanol in regular drinkers compared with nondrinkers. In women, the multivariate-adjusted HRs were 0.93 (0.80-1.08) for occasional drinkers, and 0.85 (0.74-0.99) for <23 g/d, and 1.22 (0.98-1.53) for ≥23 g/d in regular drinkers compared with nondrinkers. The HRs for proximal and distal cancer in drinkers vs nondrinkers were 1.69 (1.15-2.47) and 1.24 (0.99-1.55) for ≥92 g/d in men, and 1.60 (0.76-3.37) and 1.18 (0.88-1.57) for ≥23 g/d in women, respectively. Alcohol intake increased stomach cancer risk in men, and heavy drinkers showed a greater point estimate of risk for proximal cancer than for distal cancer.

Alcohol consumption and breast cancer risk in Japan: A pooled analysis of eight population-based cohort studies.

Although alcohol consumption is reported to increase the incidence of breast cancer in European studies, evidence for an association between alcohol and breast cancer in Asian populations is insufficient. We conducted a pooled analysis of eight large-scale population-based prospective cohort studies in Japan to evaluate the association between alcohol (both frequency and amount) and breast cancer risk with categorization by menopausal status at baseline and at diagnosis. Estimated hazard ratios (HR) and 95% confidence intervals were calculated in the individual cohorts and combined using random-effects models. Among 158 164 subjects with 2 369 252 person-years of follow-up, 2208 breast cancer cases were newly diagnosed. Alcohol consumption had a significant association with a higher risk of breast cancer in both women who were premenopausal at baseline (regular drinker compared to nondrinker: HR 1.37, 1.04-1.81, ≥23 g/d compared to 0 g/d: HR 1.74, 1.25-2.43, P for trend per frequency category: P = .017) and those who were premenopausal at diagnosis (≥23 g/d compared to 0 g/d: HR 1.89, 1.04-3.43, P for trend per frequency category: P = .032). In contrast, no significant association was seen in women who were postmenopausal at baseline or at diagnosis, despite a substantial number of subjects and long follow-up period. Our results revealed that frequent and high alcohol consumption are both risk factors for Asian premenopausal breast cancer, similarly to previous studies in Western countries. The lack of a clear association in postmenopausal women in our study warrants larger investigation in Asia.

Smoking and colorectal cancer: A pooled analysis of 10 population-based cohort studies in Japan.

Smoking has been consistently associated with the risk of colorectal cancer (CRC) in Western populations; however, evidence is limited and inconsistent in Asian people. To assess the association of smoking status, smoking intensity and smoking cessation with colorectal risk in the Japanese population, we performed a pooled analysis of 10 population-based cohort studies. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox's proportional hazards model and then pooled using a random-effects model. Among 363 409 participants followed up for 2 666 004 person-years, 9232 incident CRCs were identified. In men, compared with never smokers, ever smokers showed higher risk of CRC. The HRs (95% CI) were 1.19 (1.10-1.29) for CRC, 1.19 (1.09-1.30) for colon cancer, 1.28 (1.13-1.46) for distal colon cancer and 1.21 (1.07-1.36) for rectal cancer. Smoking was associated with risk of CRC in a dose-response manner. In women, compared with never smokers, ever smokers showed increased risk of distal colon cancer (1.47 [1.19-1.82]). There was no evidence of a significant gender difference in the association of smoking and CRC risk. Our results confirm that smoking is associated with an increased risk of CRC, both overall and subsites, in Japanese men and distal colon cancer in Japanese women.

Congenital Malformations and Perinatal Deaths Among the Children of Atomic Bomb Survivors: A Reappraisal.

From 1948 to 1954, the Atomic Bomb Casualty Commission conducted a study of pregnancy outcomes among births to atomic bomb survivors (Hiroshima and Nagasaki, Japan) who had received radiation doses ranging from 0 Gy to near-lethal levels. Past reports (1956, 1981, and 1990) on the cohort did not identify significant associations of radiation exposure with untoward pregnancy outcomes, such as major congenital malformations, stillbirths, or neonatal deaths, individually or in aggregate. We reexamined the risk of major congenital malformations and perinatal deaths in the children of atomic bomb survivors (n = 71,603) using fully reconstructed data to minimize the potential for bias, using refined estimates of the gonadal dose from Dosimetry System 2002 and refined analytical methods for characterizing dose-response relationships. The analyses showed that parental exposure to radiation was associated with increased risk of major congenital malformations and perinatal death, but the estimates were imprecise for direct radiation effects, and most were not statistically significant. Nonetheless, the uniformly positive estimates for untoward pregnancy outcomes among children of both maternal and paternal survivors are useful for risk assessment purposes, although extending them to populations other than the atomic bomb survivors comes with uncertainty as to generalizability.

Mortality among individuals exposed to atomic bomb radiation in utero: 1950-2012.

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.

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

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.

Radiation risk of incident colorectal cancer by anatomical site among atomic bomb survivors: 1958-2009.

Radiation effects on colorectal cancer rates, adjusted for smoking, alcohol intake and frequency of meat consumption and body mass index (BMI) by anatomical subsite (proximal colon, distal colon and rectum) were examined in a cohort of 105,444 atomic bomb survivors. Poisson regression methods were used to describe radiation-associated excess relative risks (ERR) and excess absolute rates (EAR) for the 1958-2009 period. There were 2,960 first primary colorectal cancers including 894 proximal, 871 distal and 1,046 rectal cancers. Smoking, alcohol intake and BMI were associated with subsite-specific cancer background rates. Significant linear dose-responses were found for total colon (sex-averaged ERR/Gy for 70 years old exposed at age 30 = 0.63, 95% confidence interval [CI]: 0.34; 0.98), proximal [ERR = 0.80, 95% CI: 0.32; 1.44] and distal colon cancers [ERR = 0.50, 95% CI: 0.04; 0.97], but not for rectal cancer [ERR = 0.023, 95% CI: -0.081; 0.13]. The ERRs for proximal and distal colon cancers were not significantly different (p = 0.41). The ERR decreased with attained age for total colon, but not for proximal colon cancer, and with calendar year for distal colon cancer. The ERRs and EARs did not vary by age at exposure, except for decreasing trend in EAR for proximal colon cancer. In conclusion, ionizing radiation is associated with increased risk of proximal and distal colon cancers. The ERR for proximal cancer persists over time, but that for distal colon cancer decreases. There continues to be no indication of radiation effects on rectal cancer incidence in this population.

Adult weight change and premenopausal breast cancer risk: A prospective pooled analysis of data from 628,463 women.

Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18-24 years and other breast cancer risk factors showed that weight gain from ages 18-24 to 35-44 or to 45-54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.95-0.98) and with oestrogen-receptor(ER)-positive breast cancer (HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.94-0.98). Weight gain from ages 25-34 was inversely associated with ER-positive breast cancer only and weight gain from ages 35-44 was not associated with risk. None of these weight gains were associated with ER-negative breast cancer. Weight loss was not consistently associated with overall or ER-specific risk after adjusting for initial weight. Weight increase from early-adulthood to ages 45-54 years is associated with a reduced premenopausal breast cancer risk independently of early-adulthood weight. Biological explanations are needed to account for these two separate factors.

Radiation risk of central nervous system tumors in the Life Span Study of atomic bomb survivors, 1958-2009.

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.

The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 in a pooled analysis of 16,024 men from 22 studies.

Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.

Historical Changes in Histological Diagnosis of Lung Cancer.

BACKGROUND: Histological classification of lung cancer is essential for investigations of carcinogenesis and treatment selection. We examined the temporal changes of lung cancer histological subtypes. METHODS: Lung cancer cases diagnosed in the Life Span Study cohort between 1958 and 1999 were collected from tumor registries (TR), mainly consisting of population-based cancer registries. A total of 1,025 cases were histologically reviewed according to the World Health Organization 2004 Classification by a panel of pathologists (PP). Sensitivity and specificity of diagnoses in TR were calculated, assuming that the diagnosis by PP was the gold standard. RESULTS: Sensitivity and specificity were 0.91 and 0.92 for adenocarcinoma (AD), respectively, and 0.92 and 0.94, respectively, for squamous cell carcinoma (SQ). They were similar for AD and SQ throughout the observation period. For small cell carcinoma (SM), sensitivity was low until about 1980 (0.47 in 1958-1969, and 0.61 in 1970-1979) and then became higher thereafter (0.98 in 1980-1989, and 0.95 in 1990-1999), whereas specificity was high during the whole period (range 0.99 to 1.00). Among 45 cases that were not reported as SM in TR but diagnosed as SM by PP, 16 cases were recorded as undifferentiated carcinoma in TR. CONCLUSION: Diagnosis of AD and SQ of lung cancer were generally consistent between TR records and PP review, but SMs tended to be coded as other histological types until the 1970s.

Circulating isoflavone and lignan concentrations and prostate cancer risk: a meta-analysis of individual participant data from seven prospective studies including 2,828 cases and 5,593 controls.

Phytoestrogens may influence prostate cancer development. This study aimed to examine the association between prediagnostic circulating concentrations of isoflavones (genistein, daidzein, equol) and lignans (enterolactone and enterodiol) and the risk of prostate cancer. Individual participant data were available from seven prospective studies (two studies from Japan with 241 cases and 503 controls and five studies from Europe with 2,828 cases and 5,593 controls). Because of the large difference in circulating isoflavone concentrations between Japan and Europe, analyses of the associations of isoflavone concentrations and prostate cancer risk were evaluated separately. Prostate cancer risk by study-specific fourths of circulating concentrations of each phytoestrogen was estimated using multivariable-adjusted conditional logistic regression. In men from Japan, those with high compared to low circulating equol concentrations had a lower risk of prostate cancer (multivariable-adjusted OR for upper quartile [Q4] vs. Q1 = 0.61, 95% confidence interval [CI] = 0.39-0.97), although there was no significant trend (OR per 75 percentile increase = 0.69, 95 CI = 0.46-1.05, ptrend = 0.085); Genistein and daidzein concentrations were not significantly associated with risk (ORs for Q4 vs. Q1 = 0.70, 0.45-1.10 and 0.71, 0.45-1.12, respectively). In men from Europe, circulating concentrations of genistein, daidzein and equol were not associated with risk. Circulating lignan concentrations were not associated with the risk of prostate cancer, overall or by disease aggressiveness or time to diagnosis. There was no strong evidence that prediagnostic circulating concentrations of isoflavones or lignans are associated with prostate cancer risk, although further research is warranted in populations where isoflavone intakes are high.

Japanese Legacy Cohorts: The Life Span Study Atomic Bomb Survivor Cohort and Survivors' Offspring.

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.

Effect of follow-up period on minimal-significant dose in the atomic-bomb survivor studies.

It was recently suggested that earlier reports on solid-cancer mortality and incidence in the Life Span Study of atomic-bomb survivors contain still-useful information about low-dose risk that should not be ignored, because longer follow-up may lead to attenuated estimates of low-dose risk due to longer time since exposure. Here it is demonstrated, through the use of all follow-up data and risk models stratified on period of follow-up (as opposed to sub-setting the data by follow-up period), that the appearance of risk attenuation over time may be the result of less-precise risk estimation-in particular, imprecise estimation of effect-modification parameters-in the earlier periods. Longer follow-up, in addition to allowing more-precise estimation of risk due to larger numbers of radiation-related cases, provides more-precise adjustment for background mortality or incidence and more-accurate assessment of risk modification by age at exposure and attained age. It is concluded that the latest follow-up data are most appropriate for inferring low-dose risk. Furthermore, if researchers are interested in effects of time since exposure, the most-recent follow-up data should be considered rather than the results of earlier reports.

Effect of evacuation on liver function after the Fukushima Daiichi Nuclear Power Plant accident: The Fukushima Health Management Survey.

BACKGROUND: The Great East Japan Earthquake and subsequent Fukushima Daiichi Nuclear Power Plant accident caused residents to switch from their normal lives to lives focused on evacuation. We evaluated liver function before and after this disaster to elucidate the effects of evacuation on liver function. METHODS: This study was a longitudinal survey of 26,006 Japanese men and women living near the Fukushima Daiichi Nuclear Power Plant. This study was undertaken using data from annual health checkups conducted for persons aged 40-90 years between 2008 and 2010. Follow-up examinations were conducted from June 2011 to the end of March 2013, with a mean follow up of 1.6 years. Changes in liver function before and after the disaster were compared among evacuees and non-evacuees. We also assessed groups according to alcohol drinking status. RESULTS: The prevalence of liver dysfunction significantly increased in all participants from 16.4% before to 19.2% after the disaster. The incidence of liver dysfunction was significantly higher in evacuees than in non-evacuees. Multivariate logistic regression analysis showed that evacuation was significantly associated with liver dysfunction among residents. CONCLUSIONS: This is the first study to show that evacuation due to the Fukushima Daiichi nuclear power plant disaster was associated with an increase in liver dysfunction.

The impact of evacuation on the incidence of chronic kidney disease after the Great East Japan Earthquake: The Fukushima Health Management Survey.

BACKGROUND: About 146,000 people were forced into long-term evacuation due to the nuclear power plant accident caused by the Great East Japan Earthquake in 2011. Disaster is known to induce hypertension in survivors for a certain period, but it is unclear whether prolonged disaster stress influences chronic kidney disease (CKD). We conducted an observational cohort study to elucidate the effects of evacuation stress on CKD incidence. METHODS: Participants were individuals living in communities near the Fukushima nuclear power plant, aged 40-74 years without CKD as of their 2011 general health checkup (non-evacuees: n = 9780, evacuees: n = 4712). We followed new-onset CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria] using general annual health checkup data from 2012 to 2014. Association between evacuation and CKD incidence was analyzed using the Cox proportional hazard model. RESULTS: Mean age of the participants at baseline was 65 years, 46.7% were men, and baseline eGFR was 75.7 ml/min/1.73 m2. During the mean follow-up period of 2.46 years, CKD incidence rate was 80.8/1000 and 100.2/1000 person-years in non-evacuees and evacuees, respectively. Evacuation was a significant risk factor of CKD incidence after adjusting for age, gender, obesity, hypertension, diabetes, dyslipidemia, smoking, and baseline eGFR [hazard ratio (HR): 1.45; 95% confidence interval (CI) 1.35-1.56]. Evacuation was significantly associated with the incidence of eGFR <60 ml/min/1.73 m2 (HR: 1.48; 95% CI 1.37-1.60), but not with the incidence of proteinuria (HR: 1.21; 95% CI 0.93-1.56). CONCLUSION: Evacuation was a risk factor associated with CKD incidence after the disaster.