Reproductive and lifestyle factors related to breast cancer among Japanese women: An observational cohort study.

The incidence of breast cancer among Japanese women is substantially increasing. This study evaluated the effects of reproductive and lifestyle factors with respect to breast cancer overall and separately among pre- and postmenopausal women using data from the Three-Prefecture Cohort Study of Japan.A total of 33,410 women aged 40 to 79 years completed a self-administered questionnaire, which included items about menstrual and reproductive history and other lifestyle factors. The follow-up period was from 1984 to 1992 in Miyagi and 1985 to 2000 in Aichi Prefectures. We used Cox proportional hazards regression models to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) after adjusting for confounding factors.After 9.8 mean years of follow-up, 287 cases of breast cancer were recorded. In the overall analysis, later menarche (≥16 years) and parity were significantly associated with a decreased risk of breast cancer, with HRs of 0.69 (95% CI 0.48-0.99) and 0.72 (95% CI 0.52-0.99), respectively. Further, there was a significant decline in the risk of breast cancer with increasing number of birth among parous women (P for trend = .010). On the contrary, a family history of breast cancer in the mother was significantly associated with an increased risk of breast cancer (HR 3.22, 95% CI 1.52-6.84). Analyses based on menopausal status at baseline indicated that height (≥160 cm) and weight (≥65 kg) were significantly associated with an increased risk of postmenopausal breast cancer, with HRs of 1.34 (95% CI 0.72-2.50) and 3.13 (95% CI 1.75-5.60), respectively. Risk associated with BMI significantly differs by menopausal status.Our findings suggest the important role of reproductive factors in the development of breast cancer in Japanese women; however, body mass index (BMI) may have different effects on breast cancer in Japanese women compared with western women.

Coffee Consumption and All-Cause and Cardiovascular Mortality　- Three-Prefecture Cohort in Japan.

BACKGROUND: Coffee, which contains various bioactive compounds, is one of the most popular beverages. Further accumulation of evidence is needed, however, to confirm whether coffee consumption would be effective in preventing cardiovascular disease in the general Japanese population. Methods and Results: We evaluated the association between coffee consumption frequency (never, sometimes, 1-2 cups/day, 3-4 cups/day and ≥5 cups/day) and mortality from all causes, heart disease, and cerebrovascular disease, in 39,685 men and 43,124 women aged 40-79 years at baseline, in a 3-prefecture cohort study. The coffee consumption frequency was assessed on questionnaire. Cox proportional hazards regression modeling was used to assess the association between coffee consumption frequency and all-cause and cardiovascular disease mortality with adjustment for potential confounders. During 411,341 and 472,433 person-years in men and women, respectively, a total of 7,955 men and 5,725 women died. Coffee consumption frequency was inversely associated with all-cause mortality in both genders (P for trend<0.001). In addition, the risks of mortality from cerebrovascular disease in men (P for trend<0.001), and heart disease in women (P for trend=0.031) were inversely associated with coffee consumption. CONCLUSIONS: In this Japanese population, coffee drinking has a preventive effect on all-cause and on cardiovascular mortality in men and/or women.

Association between coffee consumption and all-sites cancer incidence and mortality.

The preventive effect of coffee on cancer at different sites has been reported, but the effect on all-sites cancer incidence has not been extensively investigated. We evaluated the association between frequency of coffee consumption and risk of all-sites cancer incidence and mortality among 39 685 men and 43 124 women (age 40-79 years, at baseline), in the Three-Prefecture Cohort Study. The association between frequency of coffee consumption and risk of all-sites cancer incidence and mortality was assessed by a Cox proportional hazards regression model, adjusted for potential confounders. During 411 341 person-years among men and 472 433 person-years among women, a total of 4244 men and 2601 women developed cancer at different sites and a total of 3021 men and 1635 women died of cancer at different sites. We showed an inverse association between frequency of coffee consumption and all-sites cancer incidence in both men and women. Comparing participants who consumed coffee with those who never drank coffee, the adjusted hazard ratios (95% confidential interval) for all-sites cancer incidence was 0.74 (0.62-0.88) for coffee consumption of ≥5 cups/day in men (P for trend < 0.001) and 0.76 (0.58-1.02) in women (P for trend = 0.020). Coffee consumption frequency was inversely associated with mortality from all-sites cancer. In this population, increasing coffee consumption resulted in a decreased risk of all-sites cancer incidence and mortality.

Rationale, design, and profile of the Three-Prefecture Cohort in Japan: A 15-year follow-up.

BACKGROUND: We reutilized the existing Three-Prefecture Cohort to evaluate the relationship between lifestyle factors and the incidence or mortality from non-communicable diseases. METHODS: This study was a prospective population-based observation conducted from the 1980s to 2000 in three prefectures (Miyagi, Aichi, and Osaka) in Japan. The study subjects were residents aged ≥40 years who received a questionnaire. The follow-up period was 15 years from the baseline survey in each study area. A self-administered questionnaire, which included items on participants' demographic factors and lifestyle characteristics, was administered. Vital status and date of death were collected from residence certificates by the local government, and cause of death was identified using vital statistics. Cancer incidence and the date of diagnosis were collected from local cancer registry data. RESULTS: A total of 46,421 men and 54,189 women were eligible for our analysis. The person-years of follow-up for cancer incidence were 464,664 and 567,271 for men and women, respectively, and those for death were 527,940 and 648,601 for men and women, respectively. There were 8479 cancer incidences (5106 men and 3373 women) and 20,240 total deaths (11,156 men and 9084 women). The stomach was the most common cancer incidence site for both men (25.6%) and women (18.6%). The leading cause of death was cancer among men (35.0%) and cardiovascular disease among women (41.0%). CONCLUSIONS: The Three-Prefecture Cohort Study enabled us to reveal the association of multiphasic lifestyle factors with cancer incidence and mortality. The study will also allow us to conduct a pooled analysis in combination with other large-scale cohorts.

Stroke mortality associated with environmental tobacco smoke among never-smoking Japanese women: a prospective cohort study.

OBJECTIVE: This study examined the association of exposure to environmental tobacco smoke (ETS) during adulthood with stroke and its subtypes using data from a large-scale prospective cohort study in Japan. METHODS: The study population included 36,021 never-smoking Japanese women who were enrolled between 1983 and 1985 and were followed-up for 15 years. We used Cox proportional hazard regression models to estimate hazard ratios (HRs) for stroke death associated with ETS exposure at home during adulthood. RESULTS: A total of 906 cases of stroke death were observed during 437,715 person-years of follow-up. Compared with never-smoking women without smoking family members, HRs for stroke mortality among never-smoking women living with smoking family members in all subjects, in those aged 40-79 years, and in those aged ≥ 80 years were 1.14 (95% confidence interval: 0.99-1.31), 1.24 (95% CI: 1.05-1.46), and 0.89 (95% CI: 0.66-1.19), respectively, after adjustment for possible confounders. The risk was most evident for subarachnoid hemorrhage [HR: 1.66 (95% CI: 1.02-2.70) in all subjects]. CONCLUSION: This study suggests that exposure to ETS at home during adulthood is associated with an increased risk of stroke among never-smoking Japanese women.

Consumption of seafood, serum liver enzymes, and blood levels of PFOS and PFOA in the Japanese population.

OBJECTIVE: Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) have been shown to accumulate in the human body. The purpose of the present study was to examine the factors associated with the blood levels of PFOS and PFOA. METHODS: A cross-sectional study was performed on 307 men and 301 women (aged 16-76 years) living in 15 prefectures in Japan. Blood levels of PFOS and PFOA were measured by liquid chromatography-mass spectrometry. Hepatic enzymes (γ-GTP, GOT, and GPT) and ω-3 polyunsaturated fatty acids (DHA and EPA) levels in serum were also measured. Associations between the levels of PFOS and PFOA in blood and the intake frequency of 41 kinds of dishes, foods and beverages and the serum levels of liver enzymes and ω-3 polyunsaturated fatty acids were examined using rank correlations. RESULTS: Frequency of intake of boiled fish in broth, sliced raw fish and coastal fish showed significant positive correlations with PFOS concentrations in blood after adjustments for potential confounders. Serum levels of GOT, GPT, DHA and EPA showed significant positive correlations with PFOS and PFOA in blood. There was also a significant regional difference in the blood levels of PFOS and 2013PFOA, with medians being highest in the Tokai/Hokuriku/Kinki region. CONCLUSIONS: These findings suggest that the concentrations of PFOS in blood were mainly associated with fish consumption and that the levels of PFOS and PFOA were associated with the serum levels of liver enzymes in Japanese populations. Further investigations are required to clarify the reason for the regional differences in blood levels of PFOS and PFOA in Japan.

Association between blood levels of PCDDs/PCDFs/dioxin-like PCBs and history of allergic and other diseases in the Japanese population.

BACKGROUND: Previous studies reported that exposure to dioxins was associated with an increased risk of various diseases in general populations. OBJECTIVES: The aim of this study was to examine the association between levels of dioxins in blood and allergic and other diseases. METHODS: We conducted a cross-sectional study on 1,063 men and 1,201 women (aged 15-76 years), who were living throughout Japan and not occupationally exposed to dioxins, during 2002-2010. In fasting blood samples, polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like PCBs (DL-PCBs) were analyzed by isotope dilution high-resolution gas chromatography/mass spectrometry. We obtained information on life style and self-reported history of diseases using a questionnaire. Blood pressure, blood levels of hemoglobin A1c, and serum lipids were also measured. Multiple logistic regression models were used to analyze the association between dioxin levels in blood and various diseases. RESULTS: Toxic equivalents of PCDDs/PCDFs and total dioxins showed significant inverse dose-response relationships with atopic dermatitis, after adjustments for potential confounders. The highest quartile for total dioxins had an adjusted odds ratio of 0.26 (95 % confidence interval 0.08-0.70) compared to the reference group (first quartile). The odds ratios for hypertension, diabetes mellitus, hyperlipidemia, gout in men, and gynecologic diseases in women significantly increased with increasing toxic equivalents of PCDDs/PCDFs, DL-PCBs, and total dioxins in blood. CONCLUSIONS: The present findings suggest that background exposure to dioxins was associated with reduced risk of atopic dermatitis. The results also support the idea that low-level exposure to dioxins is associated with an increased risk of diabetes, hypertension, and hyperlipidemia.

An association between long-term exposure to ambient air pollution and mortality from lung cancer and respiratory diseases in Japan.

BACKGROUND: Evidence for a link between long-term exposure to air pollution and lung cancer is limited to Western populations. In this prospective cohort study, we examined this association in a Japanese population. METHODS: The study comprised 63 520 participants living in 6 areas in 3 Japanese prefectures who were enrolled between 1983 and 1985. Exposure to particulate matter less than 2.5 µm in aerodynamic diameter (PM(2.5)), sulfur dioxide (SO(2)), and nitrogen dioxide (NO(2)) was assessed using data from monitoring stations located in or nearby each area. The Cox proportional hazards model was used to calculate the hazard ratios associated with the average concentrations of these air pollutants. RESULTS: The 10-year average concentrations of PM(2.5), SO(2), and NO(2) before recruitment (1974-1983) were 16.8 to 41.9 µg/m(3), 2.4 to 19.0 ppb, and 1.2 to 33.7 ppb, respectively (inter-area range). During an average follow-up of 8.7 years, there were 6687 deaths, including 518 deaths from lung cancer. The hazard ratios for lung cancer mortality associated with a 10-unit increase in PM(2.5) (µg/m(3)), SO(2) (ppb), and NO(2) (ppb) were 1.24 (95% confidence interval: 1.12-1.37), 1.26 (1.07-1.48), and 1.17 (1.10-1.26), respectively, after adjustment for tobacco smoking and other confounding factors. In addition, a significant increase in risk was observed for male smokers and female never smokers. Respiratory diseases, particularly pneumonia, were also significantly associated with all the air pollutants. CONCLUSIONS: Long-term exposure to air pollution is associated with lung cancer and respiratory diseases in Japan.

Correlations of fish intake and plasma docosahexaenoic acid levels with each congener of PCDDs/PCDFs/dioxin-like PCBs in blood from the Japanese population.

PURPOSE: The purpose of the present study was to investigate the factors associated with blood levels of each congener of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (DL-PCBs) in the Japanese population. METHODS: A cross-sectional study was performed on 1,656 subjects (755 men and 901 women) aged 15-73 years, who were living in 90 different areas of 30 prefectures in Japan. Blood levels of 29 PCDD, PCDF, and DL-PCB congeners were determined by high-resolution gas chromatography/mass spectrometry. In addition, a questionnaire survey on life style, including dietary habit, was carried out. RESULTS: The median total toxicity equivalent (TEQ) was 17 pgTEQ/g lipid. After adjustment for age, sex, body mass index, smoking habit, and consumption of other food groups, six PCDDs/PCDFs with 4-6 substituted chlorine atoms and 10 DL-PCBs, but not HeptaCDD/F or OctaCDD, showed significant positive correlations with the frequency of intake of fish and shellfish. Furthermore, significant positive relationships were also found between plasma levels of docosahexaenoic acid (DHA), a biomarker of fish intake, and 10 PCDDs/PCDFs with 4-6 chlorine atoms and 10 DL-PCBs. The partial correlation coefficients with plasma DHA were significantly higher for DL-PCBs than for PCDDs/PCDFs, and partial correlation coefficients for PCDDs/PCDFs significantly decreased with increasing number of chlorine atoms (Spearman r = -0.80, P = 0.001). CONCLUSIONS: Blood levels of PCDDs/PCDFs with 4-6 chlorine atoms and DL-PCBs were positively associated with fish intake in the Japanese population. These results may be explained by the higher degree of bioaccumulation of these congeners in fish and shellfish in the ecosystem, and the high consumption of fish among the Japanese population.

Projected cancer mortality among Japanese males under different smoking prevalence scenarios: evidence for tobacco control goal setting.

OBJECTIVE: Male smoking prevalence is still high in Japan, and quantitative information for tobacco control is scarce. The aim of the present study was to project cancer mortality among Japanese males under different future scenarios of smoking prevalence. METHODS: The target population comprised Japanese males aged 40-79 years in 2007, whose smoking prevalence was 35%. On the basis of the pooled data from three large-scale cohort studies in Japan, the effects of age, years of smoking and years after smoking cessation on the time to all-cancer or lung cancer death were estimated by an accelerated failure time model. The parameter estimates were used to project the annual number of deaths from all cancers and lung cancer by running simulations for different future scenarios of smoking prevalence. Each scenario was evaluated by the cumulative number of avoided deaths when compared with the status quo and by the percent change (from the baseline year) in age-standardized rate of mortality. RESULTS: Reducing the smoking prevalence from 35% in 2007 to 0% in 2017 was estimated to avoid 333 900 all-cancer deaths and 171 100 lung cancer deaths in 20 years. Even when we shortened the projection period to 10 years, these numbers of avoided deaths would be 81 100 and 38 800, respectively. The age-standardized rate of all-cancer mortality was estimated to decrease by 9.6% in 10 years and 18.1% in 20 years. CONCLUSIONS: Reducing the prevalence of smoking among males would be effective in reducing the cancer burden even within 10 years in countries with a high male smoking prevalence.

Dietary patterns and blood levels of PCDDs, PCDFs, and dioxin-like PCBs in 1656 Japanese individuals.

The association between dietary patterns and blood dioxin levels has not been fully investigated. The present study population consisted of 755 men and 901 women (aged 15-73years) living in 90 different areas of 30 prefectures of Japan. Dietary habits were assessed by inquiring about the consumption frequency of 28 foods, food groups and beverages. In addition, the blood levels of 29 polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzo-furans (PCDFs), and dioxin-like polychlorinated biphenyl (DL-PCBs) congeners were determined by high-resolution gas chromatography/mass spectrometry. The median total toxicity equivalent (TEQ) in the blood, which was calculated on the basis of the toxicity equivalency factors of WHO (2005), was 16 pg TEQg(-1) lipid. Principal component analysis identified five dietary patterns: Healthy diet (high intake of vegetables and fruits); Meat/High fat intake (high intake of meat, meat products, and eggs); Seafood and Alcohol (high intake of fish, shellfish, and alcoholic beverages); Miscellaneous; and Milk products and Alcohol intake (high intake of milk, Milk products, and alcoholic beverages). After adjusting for sex, age, body mass index, and smoking habits, the Seafood and Alcohol pattern scores were significantly related to higher blood levels of total TEQ and PCDDs/PCDFs/DL-PCBs, and the Milk products and Alcohol pattern scores were correlated with higher blood levels of DL-PCBs. More detailed analysis showed that the intake frequencies for alcoholic beverages and seafood were independently and positively associated with total TEQ and the TEQ of PCDFs and DL-PCBs. The association between alcoholic beverage intake and PCDDs was also significant. Analysis of dietary patterns may be useful for identifying the dietary characteristics of individuals with a high dioxin body burden.

The effects of smoking and smoking cessation on mortality from cardiovascular disease among Japanese: pooled analysis of three large-scale cohort studies in Japan.

OBJECTIVES: To estimate the gender-specific risk of mortality from cardiovascular disease according to smoking status and time since smoking cessation among former smokers in Japan. DESIGN: Prospective study. SETTING: 140,026 males and 156,810 females aged 40-79 years who participated in one of three cohort studies conducted in Japan between 1980 and 1990. OUTCOME: The gender-specific hazard ratios (HRs) for cardiovascular disease mortality were calculated after adjustment for age and cohort. RESULTS: The age-adjusted and cohort-adjusted HRs for current smokers compared with lifelong non-smokers were 1.51 (95% CI 1.38 to 1.64) for total cardiovascular diseases, 2.19 (95% CI 1.79 to 2.67) for coronary heart disease and 1.24 (95% CI 1.10 to 1.41) for total stroke in males, and were 1.85 (95% CI 1.65 to 2.06), 2.84 (95% CI 2.24 to 3.60) and 1.70 (95% CI 1.44 to 2.01), respectively, in females. The age-adjusted and cohort-adjusted HRs for former smokers compared with current smokers according to the time period since smoking cessation decreased by approximately 5 years after smoking cessation and reached the same level as lifelong non-smokers approximately 10 years after smoking cessation among both males and females. CONCLUSIONS: The present study confirmed the association between smoking and mortality from cardiovascular disease in both males and females. Smoking cessation is a crucial preventive measure against death from cardiovascular disease.

A longitudinal study of trends in blood dioxins and dioxin-like compounds levels in residents from two locations in Japan during 2002-2006.

To investigate the recent changes in background exposure to dioxin-related compounds, the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (dl-PCBs) in the blood of individual residents in Japan were repeatedly examined. Twenty-six subjects (mean age, 52.7 +/- 1.8) from District A and 23 subjects (mean age, 56.1 +/- 1.2) from District B were longitudinally analyzed from 2002 to 2006. District A is a rural area in Osaka prefecture, and District B is an urban area in Saitama prefecture. For the longitudinal analysis of these concentrations, we used the generalized estimating equation (GEE). The PCDD + PCDF concentrations decreased significantly between 2002 and 2006 (p < 0.0001), but the concentrations of dl-PCBs declined to a smaller degree over the 5-year period. A time x body mass index (BMI) interaction suggests that the reduction rate of blood PCDDs + PCDFs and dl-PCB concentrations in subjects with a BMI greater than the 75th percentile is lower than that of subjects with a BMI less than the 75th percentile from 2002 to 2004 over the 5-year period. From other reports on the dietary intake of PCDDs, PCDFs, and dl-PCBs in Japan, the total amount of daily dioxin intake decreased, but the percentage of dl-PCBs increased yearly in the first half of the 2000s. The reason for the difference in the 5-year change in blood concentrations between PCDDs +PCDFs and dl-PCBs may be explained by the yearly change in the dietary dioxin intake.

Efficacy of oral tegafur-uracil (UFT) as adjuvant therapy as compared with classical cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in early breast cancer: a pooled analysis of two randomized controlled trials (N.SAS-BC 01 trial and CUBC trial).

Two randomized clinical studies comparing the efficacy of oral UFT (2 years) with that of classical cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (six courses) have been conducted in patients with resected early breast cancer. We have performed a pooled analysis of these two randomized studies. A pooled analysis was performed using individual patient data from the two trials. Hazard ratios (HRs) were determined with a Cox model stratified by study and adjusted for clinical characteristics. We preplanned to verify the following two hypotheses: UFT is non-inferior to CMF in all patients (hypothesis 1) or in ER-positive patients (hypothesis 2) with respect to relapse-free survival (RFS). Non-inferiority of UFT versus CMF was established if the upper limit of the two-sided confidence interval (CI) of the HR for RFS did not exceed 1.30. Hochberg multiplicity adjustment for the significance level was performed. A total of 1,057 patients were analyzed (CMF, n = 528; UFT, n = 529). Median follow-up time was 5.6 years. The HR for RFS was 1.04 (95% CI, 0.78-1.40) in all patients and 0.79 (97.5% CI, 0.49-1.27) in ER-positive patients. UFT was shown to be non-inferior to CMF in ER-positive patients. An exploratory subgroup analysis showed that RFS was better with UFT than with CMF in ER-positive patients who were 50 years or older (HR, 0.58; 95% CI, 0.34-1.01). UFT is non-inferior to CMF in terms of inhibiting recurrence of ER-positive, early breast cancer.

Prevalence of metabolic syndrome associated with body burden levels of dioxin and related compounds among Japan's general population.

BACKGROUND: Environmental exposure to some persistent organic pollutants has been reported to be associated with a metabolic syndrome in the U.S. population. OBJECTIVES: We evaluated the associations of body burden levels of dioxins and related compounds with the prevalence of metabolic syndrome among the general population in Japan. METHODS: We conducted a cross-sectional study with 1,374 participants not occupationally exposed to these pollutants, living throughout Japan during 2002-2006. In fasting blood samples, we measured biochemical factors and determined lipid-adjusted concentrations of 10 polychlorinated dibenzo-p-dioxins (PCDDs), 7 polychlorinated dibenzofurans (PCDFs), and 12 dioxin-like poly-chlorinated biphenyls (DL-PCBs) all of which have toxic equivalency factors. We also performed a questionnaire survey. RESULTS: The toxic equivalents (TEQs) of PCDDs, PCDFs, and DL-PCBs and total TEQs had significant adjusted associations with metabolic syndrome, whether or not we excluded diabetic subjects. By analyzing each component of metabolic syndrome separately, the DL-PCB TEQs and total TEQs were associated with all components, and the odds ratios (ORs) in the highest quartile of DL-PCB TEQs in four of the five components were higher than those for PCDDs or PCDFs. We also found congener-specific associations with metabolic syndrome; in particular, the highest quartiles of PCB-126 and PCB-105 had adjusted ORs of 9.1 and 7.3, respectively. CONCLUSIONS: These results suggest that body burden levels of dioxins and related compounds, particularly those of DL-PCBs, are associated with metabolic syndrome. Of the components, high blood pressure, elevated triglycerides, and glucose intolerance were most closely associated with these pollutants.

Population attributable fraction of mortality associated with tobacco smoking in Japan: a pooled analysis of three large-scale cohort studies.

BACKGROUND: Quantitative measures of the burden of tobacco smoking in Asian countries are limited. We estimated the population attributable fraction (PAF) of mortality associated with smoking in Japan, using pooled data from three large-scale cohort studies. METHODS: In total, 296,836 participants (140,026 males and 156,810 females) aged 40-79 years underwent baseline surveys during the 1980s and early 1990s. The average follow-up period was 9.6 years. PAFs for all-cause mortality and individual tobacco-related diseases were estimated from smoking prevalence and relative risks. RESULTS: The prevalence of current and former smokers was 54.4% and 25.1% for males, and 8.1% and 2.4% for females. The PAF of all-cause mortality was 27.8% [95% confidence interval (CI): 25.2-30.4] for males and 6.7% (95% CI: 5.9-7.5) for females. The PAF of all-cause mortality calculated by summing the disease-specific PAFs was 19.1% (95% CI: 16.0-22.2) for males and 3.6% (95% CI: 3.0-4.2) for females. The estimated number of deaths attributable to smoking in Japan in 2005 was 163,000 for males and 33,000 for females based on the former set of PAFs, and 112,000 for males and 19,000 for females based on the latter set. The leading causes of smoking-attributable deaths were cancer (61% for males and 31% for females), ischemic heart diseases and stroke (23% for males and 51% for females), and chronic obstructive pulmonary diseases and pneumonia (11% for males and 13% for females). CONCLUSION: The health burden due to smoking remains heavy among Japanese males. Considering the high prevalence of male current smokers and increasing prevalence of young female current smokers, effective tobacco controls and quantitative assessments of the health burden of smoking need to be continuously implemented in Japan.

Dietary intake of PCDDs/PCDFs and coplanar PCBs among the Japanese population estimated by duplicate portion analysis: a low proportion of adults exceed the tolerable daily intake.

Dietary intake of dioxins was estimated by duplicate portion analysis of consecutive 3-day food samples among 86 men and 288 women (aged 17-72 years), who were living in 75 different areas of 25 prefectures in Japan. The mean (median) intake of PCDDs+PCDFs, coplanar PCBs (co-PCBs), and total dioxins, expressed on the basis of toxicity equivalents (TEQ), was 0.46 (0.34), 0.59 (0.39), and 1.06 (0.79)pg/kg body weight/day, respectively. Dietary intake was highest in fishing areas, followed by farming and urban areas. In multiple regression analysis, TEQs of PCDDs+PCDFs, co-PCBs, and total dioxins were positively associated with age and intake amount of fish and shellfish, and milk and dairy products, and negatively associated with survey year. There were significant positive correlations between dietary intake and blood levels for TEQs of PCDDs+PCDFs, co-PCBs, and total dioxins (Pearson r=0.35-0.36). The proportion of those whose dietary intake exceeded the tolerable daily intake (TDI), set by the World Health Organization (4pg TEQ/kg/day) and European Union (2pg TEQ/kg/day), was estimated at 2.1% and 10.4%, respectively. However, these proportions were considered to be overestimated because of the effect of day-to-day within-person variation. Therefore, the ratio of within- and between-person variance was estimated by applying random effects one-way analysis of variance to repeated measurements for another group of 35 persons. When the effect of within-person variation of dietary intake was accounted for, the proportion of subjects whose long-term intake exceeded the TDI of WHO and EU decreased to 0.06% and 2.9%, respectively.

Associations of environmental exposure to dioxins with prevalent diabetes among general inhabitants in Japan.

The aim of this study was to evaluate the associations of environmental exposure to dioxins with diabetes among general inhabitants in Japan. A cross-sectional study was performed on 1374 participants, who were not occupationally exposed to dioxins, aged 15-73 years, living widely in 75 different residential areas of 25 prefectures in Japan through 2002-2006. Seven polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), 12 dioxin-like polychlorinated biphenyls (PCBs), which are assigned a toxic equivalency factor, and biochemical factors were determined in fasting blood. A questionnaire survey on life-style including past history of diseases and treatments was also performed. We examined the associations of the accumulated toxic equivalents (TEQs) of PCDDs+PCDFs, dioxin-like PCBs and total dioxins with prevalent diabetes. Simple and partial correlation analyses revealed that HbA1c correlated with the accumulated TEQs of PCDDs+PCDFs, dioxin-like PCBs and total dioxins. In logistic regression analyses, the third and the highest quartiles of dioxin-like PCBs had adjusted odds ratios (ORs) of 3.07 (95% CI 1.16-8.81) and 6.82 (95% CI 2.59-20.1) compared to the reference (first plus second quartiles). On the other hand, the highest but not the third quartiles of PCDDs+PCDFs and total dioxins had significantly higher adjusted ORs compared to the respective references. These associations persisted when the subjects with poor liver or poor renal function were removed from the analysis. This recent representative data from general inhabitants in Japan showed associations of environmental exposure to dioxins, especially dioxin-like PCBs, with diabetes.

PCDDs/PCDFs and dioxin-like PCBs: recent body burden levels and their determinants among general inhabitants in Japan.

OBJECTIVE: The objective was to grasp the recent body burden levels of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (DL-PCBs) and to investigate their determinants among general inhabitants in Japan. METHODS: This study was performed on 1374 participants aged 15-73 years, who were not occupational exposure to PCDDs/PCDFs and DL-PCBs, living widely in 75 different residential areas of 25 prefectures in Japan. Seven PCDDs, ten PCDFs, twelve DL-PCBs, which are assigned a toxicity equivalent factor, and biochemical factors were determined in fasting blood. A questionnaire survey on life-style was also performed. RESULTS: The median of total toxicity equivalent (TEQ) was 20pgTEQ/g lipid. The TEQs of PCDDs/PCDFs, DL-PCBs and total TEQ increased with age. The intake frequency of fish-and-shellfish was positively associated with the TEQ of DL-PCBs in both sexes. Current smoking was negatively related to the TEQ of DL-PCBs in male subjects but not in female subjects. Feeding status was significantly related to the TEQs of PCDDs/PCDFs, DL-PCBs and total TEQ, being lowest in breast feeding and highest in never and bottle feeding. According to the results of subgroup analysis, parity was not associated with the TEQs. CONCLUSIONS: The fish-and-shellfish consumption may contribute to the accumulation of DL-PCBs, and smoking may induce some biological action for the elimination of DL-PCBs from the human body. Breast feeding is considered to be one of the major excretory pathways of PCDDs/PCDFs and DL-PCBs in women, while parity may not largely contribute to the elimination of these pollutants.

Reduced life expectancy due to smoking in large-scale cohort studies in Japan.

BACKGROUND: To show the reduction in life expectancy due to smoking and the recovery of normal life expectancy by smoking cessation is useful for tobacco control health policy. METHODS: This study included 140,026 males and 156,810 females aged 40-79 years, who were participants of large-scale cohort studies in Japan (Japan Health Center-based Prospective Study [JPHC]-I, JPHC-II, Three-Prefecture Study, and Japan Collaborative Cohort [JACC] Study), which commenced around 1990. The mean follow-up period (+/-standard deviation) was 9.6 +/- 2.3 years, during which 16,282 men and 9,418 women died. For persons aged 40-79 years grouped according to each defined smoking status in the baseline questionnaire, sex- and age-specific death rates at attained ages were calculated. The age-specific death rate was calculated by dividing the number of persons who died at the age by the number of persons who were followed-up at the attained age. From these death rates, current life tables were constructed according to the smoking status, and survival curves were plotted. RESULTS: The life expectancy of male smokers, ex-smokers, and never-smokers at age 40 years was 38.5, 40.8, and 42.4 years respectively. In women, the corresponding life expectancies were 42.4, 42.1, and 46.1 years. In both sexes, the age by which half of the current smokers had died was approximately 4 years younger than that for never-smokers. The life expectancies of male ex-smokers who quit smoking before ages 40, 50, 60, and 70 years were 4.8, 3.7, 1.6, and 0.5 years longer than those of smokers, respectively. CONCLUSION: Smoking considerably reduced the life expectancy, and earlier smoking cessation resulted in a better survival than that seen with continued smoking.