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Sleep duration is emerging as an important modifiable risk factor for morbidity and mortality. We assessed the association between sleep duration and cancer incidence and mortality among Japanese adults using data from six population‐based cohorts with 271 694 participants. During a total follow‐up period of about 5.9 million person‐years, we identified 40 751 incident cancer cases and 18 323 cancer deaths. We computed study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models and pooled the estimates using random‐effects meta‐analysis. Sleep duration of ≥10 hours (vs 7 hours) was associated with increased risk of cancer incidence among women (HR 1.19, 95% CI 1.02‐1.38), but not men, and increased risk of cancer mortality among men (HR 1.18, 95% CI 1.00‐1.39) and women (HR 1.44, 95% CI 1.20‐1.73). Sleep duration of ≤5 hours (vs 7 hours) was not associated with cancer incidence and mortality. However, among postmenopausal women, sleep durations of both ≤5 and ≥10 hours (vs 7 hours) were associated with an increased risk of cancer mortality. Among Japanese adults, sleep duration of ≥10 hours is associated with increased risk of cancer incidence and mortality among women and cancer mortality among men. [ABSTRACT FROM AUTHOR]

The relationship between cadmium exposure, exposure‐related renal tubular dysfunction, and mortality have been reported, mainly in the residents of Cd‐contaminated areas in Japan. The aim of this study was to establish the cause–effect relationship between renal tubular dysfunction and cancer mortality in the general population in non‐contaminated areas. A 19‐year cohort study was conducted in 1110 men and 1703 women in 1993 or 1994, who lived in three cadmium‐non‐contaminated areas. Mortality risk ratios of urinary β2‐microglobulin (β2MG) and N‐acetyl‐β‐glucosaminidase (NAG) for all malignant neoplasms and specific cancers were estimated using the Fine and Gray competing risks regression model. Significant hazard ratios (HRs) for liver and pancreas cancer were observed for NAG (liver: HR corresponding to an increase of 1 IU/g cr, 1.10, 95%CI, 1.02–1.19, pancreas: HR, 1.10, 95%CI, 1.02–1.19) in men. In women, a negative HR was observed for NAG (lung cancer: HR 0.80, 95% CI, 0.67–0.96) and for β2MG (all malignant neoplasms: HR, 0.97, 95% CI, 0.93–1.00). The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium‐non‐contaminated areas in Japan. We evaluated the relationship between renal tubular damage and cancer mortality by conducting a 19‐year cohort study in three cadmium non‐polluted areas in Japan. Mortality risk of urinary β2MG and NAG for all malignant neoplasms and specific cancers was estimated. Significant hazard ratios for liver and pancreas cancer were observed for NAG in men. [ABSTRACT FROM AUTHOR]

We examined whether secondhand smoke exposure during childhood was associated with cancer mortality in adulthood among never smokers. In the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, we analyzed data from 45,722 Japanese lifetime nonsmokers aged 40–79 years with no history of cancer at baseline (1988–1990) who had completed a lifestyle questionnaire, including information on the number of family members who had smoked at home during their childhood (0, 1, 2, or ≥3 family members). A Cox proportional hazards model and competing-risks regression were used to calculate multivariable hazard ratios and subdistribution hazard ratios with 95% confidence intervals for overall and site-specific cancer mortality according to the number of family members who smoked during the participant's childhood, after adjusting for potentially confounding factors. During a median follow-up period of 19.2 years, a total of 2,356 cancer deaths were documented. Secondhand smoke exposure was positively associated with the risk of mortality from pancreatic cancer in adulthood; the multivariable hazard ratio for having 3 or more family members who smoked (as compared with none) was 2.32 (95% confidence interval: 1.14, 4.72). Associations were not evident for total cancer risk or risk of other types of smoking-related cancer. In this study, secondhand smoke exposure during childhood was associated with an increased risk of pancreatic cancer mortality in adulthood. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to examine the association between hypertension grades and the risk of total and site-specific cancer mortality among Japanese men and women., Methods: In the Japan Collaborative Cohort Study, 27,332 participants aged 40-79 years were enrolled and followed up with their mortality until 2009. According to the measured blood pressure (BP) at baseline, we classified the participants into four BP categories based on 2018 European guidelines. The Cox proportional hazard models were used to calculate the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) of total and site-specific cancer mortality according to the hypertension category., Results: During the 18.5 years of median follow-up, 1,927 cancer deaths were documented. Grade 1 (systolic blood pressure [SBP] 140-159 mmHg or diastolic blood pressure [DBP] 90-99 mmHg) and grade 2-3 hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg) were associated with an increased risk of total cancer mortality; the multivariable HRs were 1.17 (1.04-1.32) for grade 1, and 1.27 (1.09-1.47) for grade 2-3 hypertension compared to optimal and normal BP (SBP < 130 mmHg and DBP < 85 mmHg). Linear and positive associations were observed between SBP and DBP 10 mmHg increment and the risk of total cancer mortality; HRs were 1.06 (1.03-1.08) for SBP and 1.07 (1.02-1.11) for DBP of 10 mmHg increment. The excess risk was primarily found for esophageal, liver, and pancreatic cancer; the respective multivariable HRs of grade 2-3 hypertension vs optimal and normal BP were 2.57 (1.10-6.04) for esophageal, 1.67 (1.01-2.77) for liver, and 1.95 (1.17-3.23) for pancreatic cancer., Conclusion: Hypertension was associated with the increased risk of total cancer mortality, primarily of esophageal, liver, and pancreatic cancer., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The aim of the present study was to evaluate the effect of environmental cadmium (Cd) exposure indicated by urinary Cd (U-Cd) on cancer mortality in the general Japanese population. A 19-year cohort study was conducted in 1107 men and 1697 women who lived in three Cd non-polluted areas in Japan. Mortality risk ratio and 95% confidence interval (95%CI) for continuous U-Cd were estimated for all malignant neoplasms and specific cancers using a Fine and Gray competing risks regression model. The all-cause, including cancer and non-cancer mortality rates per 1000 person-years were 29.8 and 13.9 in men and women, respectively. By using Fine and Gray's method, continuous U-Cd adjusted for creatinine (+1 μg/g cre) was significantly related to mortalities for all malignant neoplasms (risk ratio = 1.06, 95%CI: 1.02-1.11) and pancreas (risk ratio = 1.13, 95%CI: 1.03-1.24) in women. In the present study, U-Cd was significantly associated with increased cancer mortality in the general Japanese population, indicating that environmental Cd exposure adversely affects the life prognosis in Cd non-polluted areas in Japan. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the effect of postprandial hyperglycemia at clinic visits on all-cause and cancer mortality independent of glycated hemoglobin (HbA1c) levels in a real-world setting in Japanese patients with type 2 diabetes. We also investigated age at death.Methods: This historical cohort study included 1582 patients with type 2 diabetes who first visited our clinic from 1995 to 1998 and continued visiting for at least 1 year. The patients were followed up through 2017. Blood glucose levels at 2 h ± 30 min post-breakfast (2h-PBBG) were measured in 926 patients during the first year. The first measurements of 2h-PBBG levels were used as a measure of postprandial hyperglycemia.Results: A total of 233 patients died. The average age at death (men/women) was 75.6/80.8 years. A total of 139 patients who had 2h-PBBG levels measured died, including 46 deaths from cancer. Multivariate Cox regression analysis showed that 2h-PBBG levels significantly predicted all-cause and cancer mortality independent of HbA1c levels.Conclusions: Postprandial hyperglycemia at clinic visits may be associated with all-cause and cancer mortality in patients with type 2 diabetes independent of HbA1c levels. As this is a small observational study, further studies are warranted to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: High lipoprotein (a) level is an established cardiovascular risk, but its association with non-cardiovascular diseases, especially cancer, is controversial. Serum lipoprotein (a) levels vary widely by genetic backgrounds and are largely determined by the genetic variations of apolipoprotein (a) gene, LPA. In this study, we investigate the association between SNPs in LPA region and cancer incidence and mortality in Japanese., Methods: A genetic cohort study was conducted utilizing the data from 9923 participants in the Japan Public Health Center-based Prospective Study (JPHC Study). Twenty-five SNPs in the LPAL2-LPA region were selected from the genome-wide genotyped data. Cox regression analysis adjusted for the covariates and competing risks of death from other causes, were used to estimate the relative risk (hazard ratios (HR) with 95% confidence intervals (CI)) of overall and site-specific cancer incidence and mortality, for each SNP., Results: No significant association was found between SNPs in the LPAL2-LPA region and cancer incidence or mortality (overall/site-specific cancer). In men, however, HRs for stomach cancer incidence of 18SNPs were estimated higher than 1.5 (e.g., 2.15 for rs13202636, model free, 95%CI: 1.28-3.62) and those for stomach cancer mortality of 2SNPs (rs9365171, rs1367211) were estimated 2.13 (recessive, 95%CI:1.04-4.37) and 1.61 (additive, 95%CI: 1.00-2.59). Additionally, the minor allele for SNP rs3798220 showed increased death risk from colorectal cancer (CRC) in men (HR: 3.29, 95% CI:1.59 - 6.81) and decreased CRC incidence risk in women (HR: 0.46, 95%CI: 0.22-0.94). Minor allele carrier of any of 4SNPs could have risk of prostate cancer incidence (e.g., rs9365171 dominant, HR: 1.71, 95%CI: 1.06-2.77)., Conclusions: None of the 25 SNPs in the LPAL2-LPA region was found to be significantly associated with cancer incidence or mortality. Considering the possible association between SNPs in LPAL2-LPA region and colorectal, prostate and stomach cancer incidence or mortality, further analysis using different cohorts is warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Smoking is well known to be a major risk factor for cancer, and to decrease the levels of aryl hydrocarbon receptor repressor (AHRR) DNA methylation. AHRR is a key regulator for AHR signaling, which is involved in chemical metabolism and cancer development. Therefore, smoking-induced AHRR DNA hypomethylation may be associated with cancer development. However, it has not been reported that association between AHHR DNA methylation and cancer mortality in Asian population. Hence, we examined whether AHRR DNA methylation levels were associated with cancer mortality in a Japanese population., Methods: This study was conducted with 812 participants (aged 38-80 years) who received a health check-up in 1990, and did not have a clinical histories. We followed up the participants until the end of 2019 (median: 27.8 years), and 100 participants died from cancer. The AHRR DNA methylation levels in peripheral blood mononuclear cells (PBMCs) were measured by the pyrosequencing method. We calculated the hazard ratio (HR) and 95% confidence interval (CI) for cancer mortality according to the baseline levels of AHRR DNA methylation., Results: We found that AHRR DNA hypomethylation was associated with a higher risk of all cancer mortality, especially smoking related cancers and lung cancer. (all cancer: HR, 1.28, 95% CI, 1.09-1.51; smoking-related cancers: HR, 1.35, 95% CI, 1.12-1.62; lung cancer: HR, 1.68, 95% CI, 1.24-2.26)., Conclusions: Smoking-induced AHRR DNA hypomethylation in PBMCs was associated with the risk of cancer mortality in Japanese population; therefore, hypomethylation of AHRR may be a useful biomarker of cancer mortality risk., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Dietary factors such as fruit and vegetables are thought to reduce the risk of cancer incidence and mortality. We investigated the effect of a diet rich in fruit and vegetables against the long-term effects of radiation exposure on the risk of cancer. A cohort of 36,228 atomic-bomb survivors of Hiroshima and Nagasaki, for whom radiation dose estimates were currently available, had their diet assessed in 1980. They were followed for a period of 20 years for cancer mortality. The joint-effect of fruit and vegetables intake and radiation exposure on risk of cancer death was examined, in additive (sum of effects of diet alone and radiation alone) and multiplicative (product of effects of diet alone and radiation alone) models. In the additive model, a daily intake of fruit and vegetables significantly reduced the risk of cancer deaths by 13%, compared to an intake of once or less per week. Radiation exposure of 1 Sievert (Sv) increased significantly the risk of cancer death by 48–49%. The additive joint-effects showed a lower risk of cancer among those exposed to 1 Sv who had a diet rich in vegetables (49%-13%=36%) or fruit (48%-13%=35%). The multiplicative model gave similar results. The cancer risk reduction by vegetables in exposed persons went from 52% (effect of radiation alone) to 32% (product of effect of vegetables and radiation), and cancer risk reduction by fruit was 52% (radiation alone) to 34% (product of effect of fruit and radiation). There was no significant evidence to reject either the additive or the multiplicative model. A daily intake of fruit and vegetables was beneficial to the persons exposed to radiation in reducing their risks of cancer death. [Copyright &y& Elsevier]

PURPOSE: In southeast Okayama Prefecture, Japan, there have been reports of a high prevalence of silicosis among refractory brick production workers. Recently, a high mortality rate of lung cancer among the local residents has been observed. Therefore, a population based case-control study was conducted concerning the relationship between silica, silicosis, and lung cancer using multiple cancer controls.METHODS: Cases and controls were restricted to male subjects and information was obtained from death certificates from 1986 to 1993 in the area. Three categories of deceased control groups were selected: a series of deaths from liver cancer, colon cancer, and cancers of other organs, which was assumed not to be related to silica exposure. Age and smoking habits were adjusted by stratified analysis using the Mantel-Haenszel odds ratio estimates. Unconditional logistic regression analysis was also conducted to control potential confounding factors; such as age and smoking habits.RESULTS: The age-, smoking-adjusted odds ratios were 1.94 (0.94–4.43) for the colon cancer control group, 2.13 (1.19–3.85) for the other cancer control group related to silica exposure, and 2.94 (1.30–8.90) and 2.69 (1.43–5.37) related to silicosis, respectively. The direct weighted average using the estimates for colon and the other cancer controls was 2.06 (1.29–3.29) for silica exposure, and 2.77 (1.60–4.77) for silicosis. Histological or cytological types of lung cancer cases were obtained from 64.1% of the subjects (118/184). As for the histologic type of lung cancer, small cell carcinoma was higher among those who had been silica-exposed workers than the unexposed lung cancer cases and the data from the general Japanese population. On chest x-ray findings, elevated lung cancer mortality compared with cancers other than lung cancer was demonstrated among patients without large opacities.CONCLUSIONS: Silica exposure increased the lung cancer mortality in the area. A high lung cancer mortality rate in the area could be explained by silica exposure and silicosis prevalence in this area. [Copyright &y& Elsevier]

Background: Evidence is limited regarding the association between low-carbohydrate diet (LCD) score and mortality among Asians, a population that consumes a large amount of carbohydrates., Objective: The present study examined the association between low-carbohydrate diet (LCD) score (based on percentage of energy as carbohydrate, fat, and protein) and the risk of total and cause-specific mortality among Asians., Design: This study was a prospective cohort study in Japan with follow-up for a median of 16.9 years involving 43008 men and 50646 women aged 45-75 years. Association of LCD score, LCD score based on animal sources of protein and fat, and LCD score based on plant sources of protein and fat with risk of mortality was assessed using Cox proportional hazards model., Results: A U-shaped association was observed between LCD score and total mortality: the multivariable-adjusted hazard ratios (HRs) (95% CI) of total mortality for lowest through highest scores were 1.00, 0.95 (0.91, 1.01), 0.93 (0.88, 0.98), 0.93 (0.88, 0.98), and 1.01 (0.95, 1.07) (P-non-linearity <0.01). A similar association was found for mortality from cardiovascular disease (CVD) and heart disease. LCD score based on carbohydrate, animal protein, and animal fat also showed a U-shaped association for total mortality (P-non-linearity <0.01). In contrast, LCD score based on carbohydrate, plant protein, and plant fat was linearly associated with lower total (HR, 0.89; 95% CI: 0.83, 0.94 for highest versus lowest quintile), CVD [0.82 (0.73, 0.92)], heart disease [0.83 (0.71, 0.98)], and cerebrovascular disease [0.75 (0.62, 0.91) mortality., Conclusions: Both LCD with high animal protein and fat and high-carbohydrate diet with low animal protein and fat were associated with higher risk of mortality. Meanwhile, LCD high in plant-based sources of protein and fat was associated with a lower risk of total and CVD mortality., Competing Interests: Conflict of interest None reported., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Short and long sleep durations are associated with mortality outcomes. The association between sleep duration and mortality outcomes may differ according to sex and age., Methods: Participants of the Japan Public Health Center-based prospective study (JPHC Study) were aged 40-69 years and had completed a detailed questionnaire on lifestyle factors. Sex- and age-stratified analyses on the association between habitual sleep duration and mortality from all-causes, cardiovascular diseases (CVD), cancer and other causes included 46,152 men and 53,708 women without a history of CVD or cancer. Cox proportional hazards regression models, adjusted for potential confounders, were used to determine hazard ratios and 95% confidence intervals., Results: Mean follow-up time was 19.9 years for men and 21.0 years for women. In the multivariable sex-stratified models, some categories of sleep durations ≥8 hours were positively associated with mortality from all-causes, CVD, and other causes in men and women compared with 7 hours. The sex- and age-stratified analyses did not reveal any major differences in the association between sleep duration and mortality outcomes in groups younger and older than 50 years of age. The only exception was the significant interaction between sleep duration and age in women for mortality from other causes., Conclusions: Sleep durations ≥8 hours are associated with mortality outcomes in men and women. Age may be an effect modifier for the association between sleep duration and mortality from other causes in women.

We examined associations between dietary diversity and all-cause and cause-specific mortality in 386 men and 413 women (age range, 60-79 years at baseline) who took part in the National Institute for Longevity Sciences-Longitudinal Study of Aging study from 1997 to 2000. Dietary intake was assessed using three-day dietary records and photographs. The Quantitative Index for Dietary Diversity was used to determine the dietary diversity among thirteen food groups. Dietary diversity score and each food intake were examined by sex-stratified tertiles, and hazard ratios (HR) were calculated to compare the risk for all-cause and cause-specific deaths across tertiles, after controlling for age, sex, body mass index, alcohol intake, smoking status, education, physical activity, and disease history. During a mean follow-up of 15.7 years, 289 subjects (36.2%) died. Compared to the subjects in the lowest tertile, the multivariate-adjusted HR for all-cause and cancer mortality was 0.69 (95% confidence interval (CI): 0.51-0.94) and 0.57 (95% CI: 0.33-0.98), respectively (trend p < 0.05), in subjects in the highest tertile of dietary diversity. There were no significant associations between dietary diversity score and death from cardiovascular or cerebrovascular disease. Eating a variety of foods might contribute to longevity in older Japanese community dwellers.

Background: The effect of smoking on mortality in working-age adults remains unclear. Accordingly, we compared the effects of cigarette smoking and smoking cessation on total and cause-specific mortality in a Japanese working population. Methods and Results: This study included 79,114 Japanese workers aged 20-85 years who participated in the Japan Epidemiology Collaboration on Occupational Health Study. Deaths and causes of death were identified from death certificates, sick leave documents, family confirmation, and other sources. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated via Cox proportional hazards regression. During a maximum 6-year follow-up, there were 252 deaths in total. Multivariable-adjusted HRs (95% CIs) for total mortality, cardiovascular disease (CVD) mortality, and tobacco-related cancer mortality were 1.49 (1.10-2.01), 1.79 (0.99-3.24), and 1.80 (1.02-3.19), respectively, in current vs. never smokers. Among current smokers, the risks of total, tobacco-related cancer, and CVD mortality increased with increasing cigarette consumption (P trend <0.05 for all). Compared with never smokers, former smokers who quit <5 and ≥5 years before baseline had HRs (95% CIs) for total mortality of 1.80 (1.00-3.25) and 1.02 (0.57-1.82), respectively., Conclusions: In this cohort of workers, cigarette smoking was associated with increased risk of death from all and specific causes (including CVD and tobacco-related cancer), although these risks diminished 5 years after smoking cessation.