Development of the Scores for Traditional and Modified Japanese Diets.

Increasing attention is being paid to the role of diet quality in the prevention and management of non-communicable diseases. We developed a scoring system for the traditional Japanese diet and its modified version considering the dietary culture in Japan, dietary guidelines for the Japanese, and updated evidence for disease prevention. The traditional Japanese diet comprises white rice, miso soup, soybean products, vegetables, mushrooms, seaweeds, fish and shellfish, high-sodium foods, and green tea. In the modified Japanese diet, unprocessed or minimally refined rice and raw vegetables, milk and dairy products, and fruits were additionally considered, while salty food was reverse-scored. The cutoff for the intake frequency of each food/food group was determined with reference to a health survey of >12,000 workers. Among the participants in the validation study, we confirmed the nutritional gradient with increasing scores in the expected direction. The scores were closely correlated with the respondents' backgrounds, including occupational factors. This simple scoring system can be used for diet quality assessments and epidemiological research.

Development, Relative Validity, and Reproducibility of a Short Food Frequency Questionnaire for the Japanese.

We have developed a short food frequency questionnaire (FFQ) for use in assessing diet quality for Japan, with special reference to the prevention of non-communicable diseases. Here, we assessed the ranking performance of this FFQ and its reproducibility. We developed a 28-item (21 food groups and 7 beverage) FFQ with consideration to both Japanese dietary culture and evidence of disease prevention. Twenty-four university faculty members participated in the validation study. They completed 3-day photographic food record and answered the FFQ on the next day of the last food record (time 1) and a week later (time 2). We calculated Spearman correlation coefficients between intakes of food groups from photographic food records and the consumption frequency from the FFQs (ranking ability) and between the consumption frequency of food groups from the FFQs (time 1 and time 2) (reproducibility). Spearman correlation coefficients between the food records and FFQ (time 1) ranged from -0.12 to 0.86 (median 0.51). These values were comparable to those in comparison with FFQ (time 2). After energy adjustment of intakes from the food records, the corresponding values were somewhat weakened for many food groups. The correlation coefficients between two FFQs ranged from 0.14 to 0.96 (median 0.79). The short FFQ showed acceptable reproducibility and ability to rank the consumption of most food groups.

The association between prenatal perfluoroalkyl substance exposure and symptoms of attention-deficit/hyperactivity disorder in 8-year-old children and the mediating role of thyroid hormones in the Hokkaido study.

BACKGROUND: Disruption of thyroid hormone (TH) levels during pregnancy contributes to attention deficit hyperactivity disorder (ADHD). Exposure to perfluoroalkyl substances (PFAS) during gestation may affect levels of maternal and neonatal TH; however, little is known about the effect of PFAS on ADHD mediated by TH. OBJECTIVES: We investigated the impact of maternal PFAS exposure on children's ADHD symptoms with the mediating effect of TH. METHODS: In a prospective birth cohort (the Hokkaido study), we included 770 mother-child pairs recruited between 2002 and 2005 for whom both prenatal maternal and cord blood samples were available. Eleven PFAS were measured in maternal serum obtained at 28-32 weeks of gestation using ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. TH and thyroid antibody, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured in maternal blood during early pregnancy (median 11 gestational weeks) and in cord blood at birth. ADHD symptoms in the children at 8 years of age were rated by their parents using the ADHD-Rating Scale (ADHD-RS). The cut-off value was set at the 80th percentile for each sex. RESULTS: Significant inverse associations were found between some PFAS in maternal serum and ADHD symptoms among first-born children. Assuming causality, we found only one significant association: maternal FT4 mediated 17.6% of the estimated effect of perfluoroundecanoic acid exposure on hyperactivity-impulsivity among first-born children. DISCUSSION: Higher PFAS levels in maternal serum during pregnancy were associated with lower risks of ADHD symptoms at 8 years of age. The association was stronger among first-born children in relation to hyperactivity-impulsivity than with regard to inattention. There was little mediating role of TH during pregnancy in the association between maternal exposure to PFAS and reduced ADHD symptoms at 8 years of age.

Prospective association of confectionery intake with depressive symptoms among Japanese workers: the Furukawa Nutrition and Health Study.

High intake of sweet foods such as cakes, cookies, chocolate and ice cream has been reported to be associated with depressive symptoms. However, prospective studies are scarce and no study has been conducted in Asian populations. We prospectively investigated the association between confectionery intake and depressive symptoms in a Japanese working population. Participants were 911 workers (812 men and 99 women; aged 19-68 years) without depressive symptoms at baseline who completed a 3-year follow-up survey. Dietary intake was assessed using a validated self-administered diet history questionnaire. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Multiple logistic regression was used to estimate the OR of depressive symptoms according to tertile of confectionery intake with adjustment for covariates. At the time of the 3-year follow-up survey, 153 (16·8 %) workers were newly identified as having depressive symptoms (CES-D score ≥ 16). Confectionery intake was significantly associated with increased odds of developing depressive symptoms. The multivariable-adjusted OR of depressive symptoms for the highest v. lowest tertile of confectionery intake was 1·72 (95 % CI 1·03, 2·86) after adjustment for covariates including dietary factors such as folate, vitamin B6, vitamin B12, n-3 PUFA, Mg, Zn and soft drink (Pfor trend = 0·012). Our results suggest that confectionery intake is associated with a higher risk of depressive symptoms in a Japanese working population predominantly comprised of men.

Diagnosis-specific Cumulative Incidence of Return-to-work, Resignation, and Death Among Long-term Sick-listed Employees: Findings From the Japan Epidemiology Collaboration on Occupational Health Study.

BACKGROUND: While it is essential to understand how long is sufficient for return-to-work when designing paid sick-leave systems, little attempt has been done to collect cause-specific information on when and how many of sickness absentees returned to work, became unemployed, or passed away. METHODS: We studied the first sick-leave episode of ≥30 consecutive days in those ≤55 years of age during 2012-2013 among employees of 11 Japanese private companies (n = 1,209), which were followed until 2017. Overall and disease-specific cumulative incidences of return-to-work, resignations, and deaths were estimated using competing risk analysis. RESULTS: During the 3.5-year period (follow-up rate: 99.9%), 1,014 returned to work, 167 became unemployed, and 27 died. Overall, return-to-work occurred within 1 year in 74.9% of all absentees and in 89.3% of those who successfully returned to work. Resignation occurred within 1 year in 8.7% of all absentees and in 62.9% of all subjects who resigned. According to ICD-10 chapters, the cumulative incidence of return-to-work ranged from 82.1% for mental disorders (F00-F99) to 95.3% for circulatory diseases (I00-I99). The cumulative incidence of return-to-work due to mental disorders ranged from 66.7% in schizophrenia (F20) to 95.8% in bipolar affective disorders (F31). Death was rarely observed except for cases of neoplasms (C00-D48), of which the cumulative incidence of death reached 14.2% by 1.5 years. CONCLUSION: Return-to-work and resignations occurred commonly within 1 year of sick leave among long-term sickness absentees in the Japanese private companies. Our findings may assist occupational physicians and employers in developing effective social protection schemes.

Smoking and Long-Term Sick Leave in a Japanese Working Population: Findings of the Japan Epidemiology Collaboration on Occupational Health Study.

BACKGROUND: Few studies have investigated the association between tobacco smoking and sick leave (SL) in Japan. METHODS: We followed 70 896 workers aged 20-59 years (60 133 males, 10 763 females) between April 2012 and March 2017. A Cox proportional hazards model was used to investigate the associations between smoking (smoking status and intensity) and long-term SL (ie, SL lasting ≥30 consecutive days). Cause-specific analyses were also conducted. RESULTS: A total of 1777 people took long-term SL during a follow-up of 307 749 person years. Compared with never-smokers, current smokers were at a higher risk of long-term SL (hazard ratio [HR] = 1.32; 95% confidence interval [CI] = 1.19 to 1.48). Cause-specific analyses revealed that current smoking was associated with a higher risk of SL due to all physical disorders (HR = 1.44, 95% CI = 1.22 to 1.69), cancer (HR = 1.49, 95% CI = 1.10 to 2.01), cardiovascular disease (CVD; HR = 2.16, 95% CI = 1.31 to 3.55), and injuries/external causes (HR = 1.83, 95% CI = 1.31 to 2.58). Former smokers were at a higher risk of SL due to cancer at a borderline significance level (HR = 1.38, 95% CI = 0.99 to 1.92). Low-intensity smoking (ie, 1-10 cigarettes smoked per day) was associated with all-cause SL, SL due to CVD, and SL due to injuries/external causes compared with never-smokers. CONCLUSION: In a large cohort of working-age Japanese, smoking was associated with a greater risk of long-term SL. Greater effort is needed to mitigate disease burden associated with smoking at workplace in Japan. IMPLICATIONS: Our study contributes to the literature on the association between smoking and SL in several ways. First, the study was conducted among a Japanese working population. While the association has been extensively studied in Western setting, few attempts have been made elsewhere. Second, cause-specific analyses were undertaken in our study. Third, we paid attention to the effect of low-intensity smoking on SL given that there is growing evidence of an elevated health risk associated with low-intensity smoking.

Prospective association of soft drink consumption with depressive symptoms.

OBJECTIVE: Consumption of soft drinks has become a serious public health issue worldwide. However, prospective evidence is limited regarding the relationship between soft drink consumption and depression, especially in Asia. The aim of this study was to investigate the prospective association between soft drink consumption and the development of depressive symptoms. METHODS: We evaluated an occupational cohort of 935 adults in Japan (2012-2016), who were free from depressive symptoms at baseline and attended a 3-y follow-up assessment. Soft drink consumption was assessed using a self-administered diet history questionnaire. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multivariate logistic regression analysis controlling for sociodemographic, lifestyle, dietary, and occupational covariates. RESULTS: Over the 3-y study period, 16.9% (158 cases) of the study participants reported depressive symptoms. Higher soft drink consumption was associated with higher odds of depressive symptoms. The multivariable-adjusted OR was 1.91 (95% CI, 1.11-3.29; Ptrend = 0.015) when comparing soft drink consumption of ≥4 cups/wk with consumption of <1 cup/wk. CONCLUSION: The present results suggested that greater consumption of soft drinks would increase the likelihood of exhibiting depressive symptoms.

Effect of prenatal exposure to per- and polyfluoroalkyl substances on childhood allergies and common infectious diseases in children up to age 7 years: The Hokkaido study on environment and children's health.

Per- and polyfluoroalkyl substances (PFAS) are widely used bio-accumulative chemicals in many industrial and household products. Experimental studies reported that exposure to PFAS results in immunotoxicity. We have previously reported that prenatal exposure to PFAS decreased the risk of allergies, while it increased the risk of infectious diseases at ages 2 and 4 years. However, it remains unclear whether the adverse effects of PFAS on allergies and infectious diseases continue until a reliable age of diagnosing allergies. This study aimed at investigating the effects of prenatal exposure to PFAS on the prevalence of allergies and infectious diseases in children up to age 7, from the Hokkaido Study. Among mother-child pairs enrolled in the Hokkaido study and followed up until the age of 7 years, 2689 participants with maternal PFAS, 1st trimester of pregnancy and 7-year-old questionnaire survey data were included in this study. Eleven PFAS in the 3rd-trimester plasma were measured using ultra-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry. Wheeze, rhino-conjunctivitis, and eczema were defined using the International Study of Asthma and Allergies on Childhood (ISAAC) questionnaire. History childhood infectious diseases diagnosed by a doctor was assessed by a mother-reported questionnaire at child's age 7. The relative risk of childhood allergies was calculated by generalized estimating equation models. The odds ratio of an episode of infectious diseases was calculated by logistic regression analysis, adjusted for potential confounders. The prevalence of various allergies and infectious diseases was: wheeze, 11.9%; rhino-conjunctivitis, 11.3%; eczema, 21.0%; chickenpox, 61.5%; otitis media, 55.7%; pneumonia, 30.6%; and respiratory syncytial virus infection, 16.8%. Prenatal exposure to perfluorooctanoic acid, perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) was inversely associated with rhino-conjunctivitis, while that for perfluorooctanoate (PFOA), perfluorooctane sulfonate, PFUnDA, perfluorododecanoic acid (PFDoDA), and perfluorotridecanoic acid was inversely associated with eczema. For infectious diseases, PFDA and PFDoDA were associated with increased risk of pneumonia and PFOA was associated with increased risk of RSV infection among children not having any siblings (only-one-child). Our results corroborate the hypothesis on immunosuppressive and immunomodulating effects of PFAS on allergies and infectious diseases in children. These effects observed previously at 2 and 4 years continued until the age of 7 years. However, additional studies assessing inflammatory biomarkers along with ISAAC questionnaires, doctor-diagnosed allergies, and longer follow-ups are necessary to better assess the effects of exposure to chemicals on human immune outcomes.

Cross-Sectional Study on the Association between Dietary Non-Enzymatic Antioxidant Capacity and Serum Liver Enzymes: The Furukawa Nutrition and Health Study.

We examined the association of dietary non-enzymatic antioxidant capacity (NEAC) in overall diet, and separately from foods and beverages, with serum liver enzymes in a Japanese working population. This cross-sectional study was conducted among 1791 employees aged 18-69 years, who underwent a comprehensive health checkup in 2012-2013. A brief validated self-administered diet-history questionnaire was used for dietary assessment, and dietary NEAC intake was determined from databases of NEAC values, obtained using ferric reducing-antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. The dietary NEAC intake was calculated by multiplying the estimated NEAC values by the amounts consumed and summing the resulting values. A multiple-regression analysis was performed to explore the association between dietary NEAC intake and the serum levels of liver enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT)), after adjustment for confounding factors. No significant associations were found between overall dietary NEAC intake and AST (FRAP, p for trend = 0.97; ORAC, p = 0.72), ALT (FRAP, p = 0.73; ORAC, p = 0.92), and GGT (FRAP, p = 0.96; ORAC, p = 0.19) levels. Food-derived, but not beverage-derived, NEAC intake was inversely associated with serum GGT levels (FRAP, p for trend = 0.001; ORAC, p = 0.02), particularly among older participants and those with high serum ferritin concentrations. The results imply that overall dietary NEAC intake is not associated with liver dysfunction, and that the NEAC values from foods may be inversely associated with serum GGT levels.

Prospective Association between Whole Grain Consumption and Hypertension: The Furukawa Nutrition and Health Study.

Hypertension has become a major public health issue worldwide. Whole grains contain higher levels and a broader range of nutrients with potential health benefits and may decrease the risk of hypertension. However, no prospective studies have investigated this association in the high-income Asia Pacific region, which has the lowest whole grain intake worldwide. Thus, we examined the prospective association between whole grain consumption and the development of hypertension in Japan. Participants included 944 working Japanese adults aged 19-68 years who had no hypertension at baseline and completed a 3-year follow-up survey. Whole grain consumption was assessed via a self-administered dietary questionnaire. Multivariate logistic regression analysis was carried out to examine the association between whole grain consumption and hypertension, adjusting for potential confounding factors, such as sociodemographic, lifestyle, dietary, and occupational characteristics. After 3 years, 9.4% (86 cases) of the study participants had developed hypertension. More frequent whole grain consumption, classified as an intake frequency of "sometimes or always", was associated with lower odds of hypertension (multivariate-adjusted odds ratio: 0.36; 95% confidence interval: 0.16-0.83; p for trend = 0.04) compared with no consumption. Consuming more whole grains may decrease the risk of developing hypertension.

Prospective study on the association between dietary non-enzymatic antioxidant capacity and depressive symptoms.

BACKGROUND & AIMS: Oxidative stress has been suggested to play an important role in the pathophysiology of depression, and a diet high in antioxidants may improve mood. However, studies addressing this issue are scarce. The aim of this cohort study was to investigate the prospective association between dietary non-enzymatic antioxidant capacity (NEAC) in overall diet and depressive symptoms in Japanese employees. Additionally, we examined the association separated by dietary NEAC sources. METHOD: Participants were 911 workers without depressive symptoms at baseline and participated in 3-y follow-up survey. Dietary NEAC was determined from a database of NEAC measurements obtained by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC). Dietary NEAC was calculated by multiplying the estimated NEAC values with the consumed amount and summing up those values. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Logistic regression was used to estimate odds ratios of depressive symptoms according to overall NEAC and separately from foods and beverages. RESULTS: At 3-y follow-up, 153 (16.8%) workers were newly identified as having depressive symptom. No significant associations were found between higher level of overall dietary NEAC and decreased risk of depressive symptoms after adjustment for potential confounders (overall: FRAP, P for trend = 0.19 and ORAC, P for trend = 0.20). Likewise, neither higher dietary NEAC from foods nor beverages were related with lower depressive symptoms. CONCLUSION: Our findings did not support an inverse association between dietary NEAC and the risk of depressive symptoms in Japanese workers.

Prenatal exposure to 11 perfluoroalkyl substances and fetal growth: A large-scale, prospective birth cohort study.

BACKGROUND: Prenatal maternal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) has been reportedly associated with decreased birth weight. Although a majority of epidemiological studies concerning perfluoroalkyl substances (PFAS) have focused on PFOS and PFOA, epidemiological studies of PFAS with longer carbon chains are scarce. In this study, we investigated whether prenatal maternal exposure to 11 PFAS, in particular those with longer carbon chains, is associated with fetal growth. METHODS: The study included 1985 mother-infant pairs (inclusive of preterm and post-term infants), who enrolled in a large-scale, prospective birth cohort study in any of the 37 hospitals in Hokkaido, Japan between 2003 and 2009. The concentration of 11 PFAS was measured in maternal plasma collected during the third trimester of pregnancy, using ultra-performance liquid chromatography in combination with triple quadrupole mass spectrometry. Associations between the measured PFAS values and weight, length, and head circumference of all newborns at birth were examined using multiple regression analyses with adjustment for potential confounders based on data collected from medical records, questionnaires, and those for maternal plasma samples. RESULTS: Of the 11 PFAS analyzed, prenatal perfluorononanoic acid (PFNA) [per log10-unit: regression coefficient (ß) = -96.2 g, 95% confidence intervals (95% CI), -165.3 to -27.1] and perfluorodecanoic acid (PFDA) (ß = -72.2 g, 95% CI, -138.1 to -6.3) concentrations were inversely associated with birth weight. Furthermore, PFNA concentrations were inversely associated with birth length (per Log10 unit: ß = -0.48 cm, 95% CI; - 0.86 to -0.11). Maternal perfluorotridecanoic acid (PFTrDA) exposure showed a significant inverse association with birth weight only for female infants (per Log10 unit: ß = -99.8 g, 95% CI, - 193.7 to -6.0) (P for interaction = 0.04). CONCLUSIONS: Our findings suggest that prenatal, maternal exposure to PFAS with longer carbon chains tends to be inversely associated with birth size of newborn infants, which may indicate that these commercially used compounds have an adverse effect on fetal growth.

Association between anthropometric indices of obesity and risk of cardiovascular disease in Japanese men.

OBJECTIVES: We aimed to compare the association of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with risk of cardiovascular disease (CVD) among middle-aged working Japanese men. METHODS: A nested case-control study was performed among middle-aged male employees who underwent periodic health checkup. A total of 241 CVD cases were identified and matched individually on age, gender, and worksite with 1205 controls. Data on BMI, WC, WHtR, smoking, hypertension, diabetes, and dyslipidemia collected at 4 years before the event/index date were retrieved. Associations between BMI, WC, WHtR, and CVD risk were assessed by using conditional logistic regression models. RESULTS: The strength of the association of BMI, WC, and WHtR with CVD risk was similar. The smoking-adjusted odds ratio (95% confidence interval) for CVD was 1.60 (1.38-1.85), 1.53 (1.33-1.78), and 1.56 (1.35-1.81) for a 1 SD unit increase in BMI, WC, and WHtR respectively. After further adjustment for hypertension, diabetes, and dyslipidemia, these associations were attenuated but remained statistically significant. CONCLUSIONS: Measures of general (BMI) and abdominal (WC and WHtR) obesity were similarly associated with CVD in middle-aged Japanese men.

Five-year cumulative incidence of overweight and obesity, and longitudinal change in body mass index in Japanese workers: The Japan Epidemiology Collaboration on Occupational Health Study.

OBJECTIVE: The present study aimed to estimate cumulative incidence of overweight and obesity and describe 5-year longitudinal changes in body mass index (BMI) in a large occupational cohort in Japan. METHODS: Participants were 55 229 Japanese employees, who were aged 20-59 years and attended at all subsequent annual health check-ups between 2009 and 2014. Mixed model analysis was performed to examine the effects of age and cohort by gender on BMI change, with age as a random variable. Cumulative incidence of overweight (23.0≤ BMI <27.5 kg/m2 ) and obesity (BMI ≥27.5 kg/m2 ) was calculated. Logistic regression analysis was used to estimate odds ratios for the incidence of overweight and obesity according to age group. RESULTS: The incidence of overweight and obesity was approximately double in men (28.3% and 6.7%, respectively) compared to women (14.3% and 3.9%, respectively).The incidence of obesity decreased with age in men, but did not differ according to age in women (P for trend: .02 and .89, respectively). Among overweight participants, the incidence of obesity was higher in women (18.9%) than men (14.5%) and decreased with advancing age (P for trend: <.001 in men and .003 in women). Mean BMI was higher in men than women in all age groups throughout the period. Younger cohorts tended to have a higher BMI change compared with older cohorts. CONCLUSIONS: In this Japanese occupational cohort, transition from overweight to obesity is higher in women than men, and the more recent cohorts had a higher change in mean BMI than the older cohorts.

Obesity and risk of hearing loss: A prospective cohort study.

BACKGROUND & AIMS: The existing yet limited prospective studies reported conflicting results about obesity and hearing loss. We investigated the prospective association between obesity and hearing loss in a large-scale Japanese working population, as well as the association between metabolic phenotype and hearing loss. METHODS: The study included 48,549 employees aged 20-64 years and free of hearing loss at baseline. Pure-tone audiometric testing was performed annually to identify hearing loss at 1 and 4 kHz. Cox proportional hazards regression was used to investigate the risk of hearing loss associated with body mass index (BMI) and metabolic phenotype (based on a BMI of ≥25.0/<25.0 kg/m2 and presence/absence of ≥2 components of metabolic syndrome, except waist circumference). Baseline and updated information were obtained from annual health checkups. RESULTS: With a median follow-up of 7 years, 1595 and 3625 individuals developed unilateral hearing loss at 1 and 4 kHz, respectively. The adjusted hazard ratios (HR) for hearing loss at 1 kHz were 1.21 (1.08, 1.36) and 1.66 (1.33, 2.08) for those with BMI 25.0-29.9 kg/m2 and BMI ≥30.0 kg/m2, respectively, compared to individuals with BMI <25.0 kg/m2. For hearing loss at 4 kHz, the corresponding HRs were 1.14 (1.05, 1.23) and 1.29 (1.09, 1.52). Compared with metabolically healthy non-obese individuals, the adjusted HRs for hearing loss at 1 kHz were 1.19 (1.03, 1.39), 1.27 (1.01, 1.61), and 1.48 (1.25, 1.76) for unhealthy non-obese, healthy obese, and unhealthy obese individuals, respectively. For hearing loss at 4 kHz, the corresponding HRs were 1.13 (1.04, 1.25), 1.21 (1.04, 1.41), and 1.26 (1.12, 1.41). CONCLUSIONS: Overweight and obesity are associated with an increased risk of hearing loss, and metabolically unhealthy obesity may confer additional risk.

Meat subtypes and colorectal cancer risk: A pooled analysis of 6 cohort studies in Japan.

Red meat and processed meat have been suggested to increase risk of colorectal cancer (CRC), especially colon cancer. However, it remains unclear whether these associations differ according to meat subtypes or colon subsites. The present study addressed this issue by undertaking a pooled analysis of large population-based cohort studies in Japan: 5 studies comprising 232 403 participants (5694 CRC cases) for analysis based on frequency of meat intake, and 2 studies comprising 123 635 participants (3550 CRC cases) for analysis based on intake quantity. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazards model and then pooled using the random effect model. Comparing the highest vs lowest quartile, beef intake was associated with an increased risk of colon cancer in women (pooled HR 1.20; 95% CI, 1.01-1.44) and distal colon cancer (DCC) risk in men (pooled HR 1.30; 95% CI, 1.05-1.61). Frequent intake of pork was associated with an increased risk of distal colon cancer in women (pooled HR 1.44; 95% CI, 1.10-1.87) for "3 times/wk or more" vs "less than 1 time/wk". Frequent intake of processed red meat was associated with an increased risk of colon cancer in women (pooled HR 1.39; 95% CI, 0.97-2.00; P trend = .04) for "almost every day" vs "less than 1 time/wk". No association was observed for chicken consumption. The present findings support that intake of beef, pork (women only), and processed red meat (women only) might be associated with a higher risk of colon (distal colon) cancer in Japanese.

Higher Dietary Non-enzymatic Antioxidant Capacity Is Associated with Decreased Risk of All-Cause and Cardiovascular Disease Mortality in Japanese Adults.

BACKGROUND: Few studies have assessed associations of non-enzymatic antioxidant capacity (NEAC) in the overall diet with all-cause or specific mortality, and their results have been inconsistent. OBJECTIVES: The present study investigated the association between dietary NEAC and all-cause or cause-specific mortality. METHODS: The study was a large-scale population-based prospective cohort study in Japan consisting of 42,520 men and 50,207 women aged 44-76 y, who had no history of cancer, stroke, ischemic heart disease, or chronic liver disease. We evaluated FFQ-based dietary NEAC with use of published databases in which the NEACs of individual foods were analyzed by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Dietary NEAC was calculated by multiplying the estimated NEAC with the consumed amount and summing up those values for all foods, and was categorized in quartiles. We identified death and cause of death with use of residential registry and death certificates. HRs and 95% Cls for death from the second survey, which was conducted from April 1995 to December 2014 were estimated with Cox proportional hazards regression analysis. RESULTS: After 1,498,308 person-years of follow-up, 12,978 total deaths occurred. The multivariable-adjusted HRs (95% Cls) for all-cause mortality for the highest compared with the lowest quartile of FRAP and ORAC were 0.85 (0.80, 0.89) and 0.84 (0.79, 0.89), respectively. Dietary NEACs were inversely associated with mortality from cardiovascular disease (CVD), but not from cancer. The multivariable-adjusted HRs (95% Cls) for CVD for the highest compared with the lowest quartile of FRAP and ORAC were 0.83 (0.75, 0.92) and 0.79 (0.70, 0.89), respectively. CONCLUSIONS: Higher dietary NEACs from FRAP and ORAC were associated with lower risk of all-cause mortality and mortality from CVD in Japanese adults.

Association between perfluoroalkyl substance exposure and thyroid hormone/thyroid antibody levels in maternal and cord blood: The Hokkaido Study.

BACKGROUND: Thyroid antibodies (TAs) are the most common cause of hypothyroidism during gestation. Although previous studies found that prenatal exposure to perfluoroalkyl substances (PFASs) disrupts thyroid hormones (THs) in humans, their effects on TAs during the perinatal period have not been investigated. OBJECTIVE: To explore the associations between prenatal exposure to eleven different PFASs from two different groups (carboxylates and sulfonates) and the expression of THs and TAs in maternal and cord blood while considering maternal TA status. METHODS: In a prospective birth cohort (the Hokkaido Study), we included 701 mother­neonate pairs recruited in 2002-2005 for whom both prenatal maternal and cord blood samples were available. Eleven PFASs were measured in maternal plasma obtained at 28-32 weeks of gestation using ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. THs and TAs including thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured in maternal blood during early pregnancy (median 11 gestational weeks), and in cord blood at birth. RESULTS: The median levels of TgAb and TPOAb in maternal serum were 15.0 and 6.0 IU/mL, respectively. The median TgAb level in neonates was 38.0 IU/mL, and TPOAb were detected in only 12.3% of samples. Maternal FT3 level was positively associated with PFAS levels in both TA-positive and TA-negative mothers. Maternal perfluorooctanoate was inversely associated with maternal TPOAb. Among boys, some maternal PFASs were associated with higher TSH and lower FT3 levels in maternal TA-negative group, while perfluorodecanoic acid was associated with lower TSH in maternal TA-positive group. Among girls, some PFAS of mothers showed associations with lower TSH and higher FT3 in maternal TA-negative group, while perfluorododecanoic acid was associated with lower FT4 in maternal TA-positive. Maternal PFASs showed associations with boy's TgAb inversely in maternal TA-negative group and with girl's TgAb positively in maternal TA-positive group. CONCLUSIONS: Our results suggest thyroid disrupting effects of PFAS exposure and susceptibility vary depending on maternal TA levels.

Relationship between dietary non-enzymatic antioxidant capacity and type 2 diabetes risk in the Japan Public Health Center-based Prospective Study.

OBJECTIVE: Intake of antioxidants may reduce the risk for type 2 diabetes (T2D) by reducing oxidative stress. However, it is unclear whether dietary non-enzymatic antioxidant capacity (NEAC), which represents the cumulative action of dietary antioxidants and their synergistic effects in foods, is associated with decreased T2D risk. The aim of this study was to investigate the associations between dietary NEAC and T2D. METHODS: The study included 64 660 adults (27 809 men and 36 851 women), 44 to 76 y of age without history of T2D in the Japan Public Health Center-based Prospective Study. Dietary NEAC was estimated using databases of NEAC measurements compiled from results for three different assays: ferric reducing-antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and total radical-trapping antioxidant parameter (TRAP). A multiple logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of self-reported physician-diagnosed T2D over 5 y with adjustment for potential confounders. RESULTS: In all, 1191 cases of newly diagnosed T2D were reported. Dietary NEACs were not significantly associated with T2D. The multivariate-adjusted ORs were 1.04 (95% CI, 0.88-1.23; Ptrend = 0.56) for FRAP, 1.11 (95% CI, 0.93-1.32; Ptrend = 0.26) for ORAC, and 0.99 (95% CI, 0.84-1.18; Ptrend = 0.84) for TRAP. Similar associations were observed in men and women (Pinteraction = 0.46 for FRAP, 0.35 for ORAC, and 0.63 for TRAP). In stratified analyses of major prooxidant factors, no notable associations with smoking and obesity status were observed. CONCLUSIONS: This finding suggests that dietary NEAC may not be appreciably associated with T2D in Japanese adults.

Leisure-time physical activity and DNA damage among Japanese workers.

BACKGROUND: It remains unclear whether daily physical activity is associated with DNA damage. This cross-sectional study examined the association between leisure-time physical activity and urinary 8-hydroxydeoxyguanosine (8-OH-dG), a biomarker of oxidative DNA damage, or urinary 7-methylguanine (m7Gua), a biomarker of methylating DNA damage. METHODS: Participants included 501 workers (294 men and 207 women), aged 20-65 years, from municipal offices in Japan. Urinary 8-OH-dG and m7Gua were measured using column-switching HPLC. Physical activity was evaluated using a self-reported questionnaire. The associations between leisure-time physical activity and urinary DNA damage markers were assessed by multiple linear regression analysis, with stratification by occupational physical activity. RESULTS: After adjusting for covariates, leisure-time physical activity showed a suggestive inverse correlation with urinary 8-OH-dG levels (P for trend = 0.06), and a significant inverse association with urinary m7Gua levels (P for trend = 0.03). In analysis stratified by occupation, inverse correlations were observed in sedentary workers (walking < 30 min/day at work: P for trend = 0.06 and = 0.03 for urinary 8-OH-dG and m7Gua, respectively), but not in physically active workers (walking ≥ 30 min/day at work). In analysis for each intensity of leisure-time physical activity, light-intensity exercise was associated with lower levels of urinary 8-OH-dG (P for trend = 0.03), whereas moderate-to-high-intensity exercise was associated with lower levels of urinary m7Gua (P for trend = 0.02). CONCLUSIONS: Our results suggest that high levels of leisure-time physical activity are associated with decreased levels of DNA damage in individuals with low physical activity at work.