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Abstract Atherosclerosis has been considered as the main cause of morbidity, mortality, and disability worldwide. The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning, which has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen. It was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke (AIS), transient ischemic attack, diabetes mellitus (DM), cardiovascular disease, chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were higher than those of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The results of the Japan Public Health Center-based Prospective Study indicated that this antibody marker is deemed useful as risk factors for AIS.

Background: The associations between the types/amounts of beverages consumed in daily life and measures of the glycemia status were investigated in a Japanese population-based cohort. Methods: Data from the baseline survey of the Japan Public Health Center-based Prospective Diabetes cohort were used. A cross-sectional analysis was performed in 3852 men and 6003 women who were evaluated under the fasting condition. The daily consumptions of coffee, green tea, oolong tea, black tea, soft drinks, fruit juices, or plain water were assessed using a self-reported questionnaire. Multivariable-adjusted linear regression analyses were performed using measures of the glycemia status (fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) ) as dependent variables and the types/amounts of beverages consumed as the independent variables, to calculate the differences according to the types/amounts of beverages consumed. Results: In the multivariable-adjusted models, coffee consumption of ≥240 mL/day was significantly associated with a change of the FPG level by −1.9 mg/dL in men (p = 0.013) and −1.4 mg/dL in women (p = 0.015), as compared to coffee consumption of 0 mL/day. No significant association of the FPG level was observed with any of the other types/amounts of beverages consumed. On the other hand, significant associations were found between the HbA1c levels and consumption of several types of beverages. Conclusions: High coffee consumption was associated with lower FPG levels in this Japanese population. Some unexpected associations of the HbA1c levels with the consumption of some types of beverages were observed, which need to be further investigated.

Abstract Prior studies reported the association of reproductive factors with breast cancer (BC), but the evidence is inconsistent. We conducted a pooled analysis of nine cohort studies in Japan to evaluate the impact of six reproductive factors (age at menarche/age at first birth/number of births/age at menopause/use of female hormones/breastfeeding) on BC incidence. We conducted analyses according to menopausal status at the baseline or at the diagnosis. Hazard ratio (HR) and 95% confidence interval (CI) were estimated by applying Cox proportional‐hazards model in each study. These hazard ratios were integrated using a random‐effects model. Among 187,999 women (premenopausal: 61,113, postmenopausal: 126,886), we observed 873 premenopausal and 1,456 postmenopausal cases. Among premenopausal women, use of female hormones significantly increased BC incidence (HR: 1.53 [1.04–2.25]). Although P value for trend was not significant for age at first birth and number of births (P for trend: 0.15 and 0.30, respectively), women giving first birth at ages ≥36 experienced significantly higher BC incidence than at ages 21–25 years, and women who had ≥2 births experienced significantly lower BC incidence than nulliparous women. Among postmenopausal women, more births significantly decreased BC incidence (P for trend: 0.03). Although P value for trend was not significant for age at first birth and age at menopause (P for trend: 0.30 and 0.37, respectively), women giving first birth at ages 26–35 years experienced significantly higher BC incidence than at ages 21–25 years, and women with age at menopause: ≥50 years experienced significantly higher BC incidence than age at menopause: ≤44 years. BC incidence was similar according to age at menarche or breastfeeding history among both premenopausal and postmenopausal women. In conclusion, among Japanese women, use of female hormones increased BC incidence in premenopausal women, and more births decreased BC incidence in postmenopausal women.

Abstract Little is known about the risk of cerebrovascular disease in cancer survivors. We aimed to assess the association between incident cancer and the subsequent risk of stroke using a large-scale, population-based prospective study. 74,530 Japanese aged between 40 and 69 years at baseline study were matched by the status of cancer diagnosis during follow-up using propensity score nearest-neighbor matching with allowance for replacement. A total of 2242 strokes were reported during 557,885 person-years of follow-up. Associations between incident cancer and the subsequent risk of all strokes, cerebral infarction, and intracerebral hemorrhage were assessed using a Cox proportional hazards model stratified on the propensity score-matched pairs. No significant association was observed between the status of cancer diagnosis of all types, gastric, colorectal and lung cancer, and subsequent occurrence of all strokes, cerebral infarction, and intracerebral hemorrhage. However, analysis by discrete time periods suggested an elevated risk in cancer patients for one to three months after a cancer diagnosis in all stroke (HR, 2.24; 95% CI, 1.06, 4.74) and cerebral infarction (HR, 2.62; 95% CI, 1.05, 6.53). This prospective cohort study found no association between the status of cancer diagnosis and the subsequent occurrence of all strokes and its subtypes during the entire follow-up period but suggested an increase in stroke risk during the active phase of malignancy.

Abstract This population-based cross-sectional study was performed to determine the mean corneal endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX), and their associations with myopia in Japanese adults living in Chikusei city. Of 7109 participants with available data, 5713 (2331 male and 3382 female) participants were eligible for analysis. After assessing the relationship between participant characteristics and spherical equivalent refraction (SER), the association of SER with the abnormal value of ECD (

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.

Abstract Physical activity is associated with subjective well-being. In rural communities, however, physical activity may be affected by environmental factors (e.g., nature and socioecological factors). We examined the association of two physical activities in rural life (farming activity and snow removal) with subjective well-being in terms of happiness and ikigai (a Japanese word meaning purpose in life). In this cross-sectional study, we analysed data collected from community-dwelling adults aged ≥ 40 years in the 2012–2014 survey of the Uonuma cohort study, Niigata, Japan. Happiness (n = 31,848) and ikigai (n = 31,785) were evaluated with respect to farming activity from May through November and snow removal from December through April by using an ordinal logistic regression model with adjustments for potential confounders. The analyses were conducted in 2019. Among the participants who reported some farming or snow-removal time, median farming and snow-removal time (minutes per day) was 90.0 and 64.3 for men and 85.7 and 51.4 for women, respectively. Ordinal logistic regression analysis showed that longer time farming was associated with greater happiness and ikigai in men (adjusted odds ratio for first vs. fourth quartile: happiness = 1.17, 95% confidence interval [CI] = 1.01, 1.35; ikigai = 1.29, 95% CI = 1.10, 1.50), and also in women (adjusted odds ratio for first vs. fourth quartile: happiness = 1.17, 95% CI = 1.001, 1.36; ikigai = 1.42, 95% CI = 1.20, 1.67). More snow-removal time was inversely associated with happiness and with ikigai in women only (adjusted odds ratio for first vs. fourth quartile: happiness = 0.75, 95% CI = 0.67, 0.85; ikigai = 0.78, 95% CI = 0.69, 0.88). Our findings showed that physical activity in rural life was associated with happiness and with ikigai, and gender differences were observed in their associations with more snow-removal time. These results may be useful in helping to identify people in rural communities who are vulnerable in terms of psychological well-being.

Abstract The beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on depression are not definitively known. In a previous population-based prospective cohort study, we found a reverse J-shaped association of intake of fish and docosapentaenoic acid (DPA), the intermediate metabolite of EPA and DHA, with major depressive disorder (MDD). To examine the association further in a cross-sectional manner, in the present study we analyzed the level of plasma phospholipid n-3 PUFAs and the risk of MDD in 1,213 participants aged 64–86 years (mean 72.9 years) who completed questionnaires and underwent medical check-ups, a mental health examination, and blood collection. In multivariate logistic regression analysis, odds ratios and 95% confidence intervals were calculated for MDD according to plasma phospholipid n-3 PUFA quartiles. MDD was diagnosed in 103 individuals. There were no significant differences in any n-3 PUFAs (i.e., EPA, DHA, or DPA) between individuals with and without MDD. Multivariate logistic regression analysis showed no significant association between any individual n-3 PUFAs and MDD risk. Overall, based on the results of this cross-sectional study, there appears to be no association of plasma phospholipid n-3 PUFAs with MDD risk in the elderly Japanese population.

Background: Although the consumption of vegetables and fruits is reported to influence the risk of cataract, no prospective study of this association from Asia has yet appeared. Here, we investigated the association between vegetable and fruit intake and cataract incidence in a large-scale population-based prospective cohort study in Japan. Methods: This study included 32,387 men and 39,333 women aged 45–74 years who had no past history of cataract and had completed a dietary questionnaire of the Japan Public Health Center-based Prospective Cohort Study. The incidence of cataract was evaluated after 5-year follow-up. We used multiple logistic regression analyses to estimate the sex-specific odds ratios (ORs), with adjustment for confounding factors. Results: We identified 1,836 incident cataracts in 594 men and 1,242 women. In men, the OR for cataract was decreased with higher intake of vegetables (ORQ5 vs Q1, 0.77; 95% confidence interval [CI], 0.59–1.01; Ptrend across quartile categories = 0.03) and cruciferous vegetables (ORQ5 vs Q1, 0.74; 95% CI, 0.57–0.96; Ptrend = 0.02). In contrast, the OR for cataract was increased with higher intake of vegetables among women (ORQ5 vs Q1, 1.28; 95% CI, 1.06–1.53; Ptrend = 0.01). Green and yellow vegetable and fruit intake were not associated with cataract in either sex. Conclusions: This study suggests that vegetables may reduce the risk of cataract in men, but not in women.

Abstract Background Although preclinical studies suggest that fermented soy foods may have a protective effect against breast cancer, no prospective cohort studies have examined this association. Objective Our study examined the association between fermented and nonfermented soy food intake and breast cancer risk using a population‐based prospective cohort study in Japan. Methods We included a total of 47,614 women aged 45–74 years in an analysis of the Japan Public Health Center‐based Prospective Study (JPHC Study). A validated food frequency questionnaire (FFQ) was used for the assessment of dietary intake. Breast cancer incidence was analyzed by multivariate Cox proportional hazards regression models. Results During an average of 15.5 years of follow‐up, 825 breast cancer cases were newly identified. We found no association of intake of soy foods with breast cancer risk, regardless of fermentation, with multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for the highest quartiles of fermented and nonfermented soy food intake of 0.94 (0.67, 1.32) and 1.15 (0.85, 1.57) compared with the lowest quartile (p for trend = 0.305 and 0.393). Unlike nonfermented soy, higher intake of fermented soy foods was associated with a significant decrease in the risk of nonlocalized breast cancer. The HR and 95% CI in the highest compared to lowest intake category of fermented soy foods was 0.53 (0.28, 0.99) versus nonfermented soy foods 0.85 (0.51, 1.42) (p for trend = 0.026 and 0.797). Conclusions Our analyses showed that fermented soy foods had no association with overall breast cancer but may be associated with decreased risk of nonlocalized breast cancer.

Background: The association between meat, fish, or fatty acid intake and acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) has been investigated in a few studies, and the results were inconsistent. In addition, most studies are mainly based on the United States and European countries, in which the dietary patterns differ from that in Asia. Therefore, the risk of AML/MDS from meat, fish, or fatty acid intake in Asia requires further exploration. The aim of this study was to investigate the association between AML/MDS incidence and meat, fish, or fatty acid intake using the Japan Public Health Center–based prospective study. Methods: The present study included 93,366 participants who were eligible for analysis and followed up from the 5-year survey date until December 2012. We estimated the impact of their intake on AML/MDS incidence using a Cox proportional hazards model. Results: The study participants were followed up for 1,345,002 person-years. During the follow-up period, we identified 67 AML and 49 MDS cases. An increased intake of processed red meat was significantly associated with the incidence of AML/MDS, with a hazard ratio of 1.63 (95% confidence interval, 1.03–2.57) for the highest versus lowest tertile and a Ptrend of 0.04. Meanwhile, the intake of other foods and fatty acids was not associated with AML/MDS. Conclusion: In this Japanese population, processed red meat was associated with an increased incidence of AML/MDS.

The relationship between the expression of microRNAs (miRNAs) in blood and a variety of diseases has been investigated. MiRNA-based liquid biopsy has attracted much attention, and cancer-specific miRNAs have been reported. However, the results of analyses of the expression of these miRNAs vary among studies. The reproduction of results regarding miRNA expression levels could be difficult if there are differences in the data acquisition process. Previous studies have shown that the anticoagulant type used during plasma preparation and sample storage conditions could contribute to differences in measured miRNA levels. Thus, the impact of these preanalytical conditions on comprehensive miRNA expression profiles was examined. First, the miRNA expression profiles of samples obtained from healthy volunteers were analyzed using next-generation sequencing. Based on an analysis of the library concentration, human genome identification rate, ratio of unique sequences and expression profiles, the optimal preanalytical conditions for obtaining highly reproducible miRNA expression profiles were established. The optimal preanalytical conditions were as follows: ethylenediaminetetraacetic acid (EDTA) as the anticoagulant, whole-blood storage at room temperature within 6 hours, and plasma storage at 4°C or -20°C within 30 days. Next, plasma samples were collected from 60 cancer patients (3 facilities × 20 patients/facility), and miRNA expression profiles were analyzed. There were no significant differences in measurements except in the expression of erythrocyte-derived hsa-miR-451a. However, the variation in hsa-miR-451a levels was smaller among facilities than among individuals. This finding suggests that samples obtained from the same facility could show significantly different degrees of hemolysis across individuals. We found that the standardization of anticoagulant use and storage conditions contributed to reducing the variation in sample quality across facilities. The findings from this study could be useful in developing protocols for collecting samples from multiple facilities for cancer screening tests.

Abstract Aims/Introduction The aim of the current study was to prospectively evaluate the association between passive smoking from a spouse and the risk of diabetes among never‐smoking Japanese women. Passive smoking at a workplace (or public facilities) was assessed as a secondary measure. Materials and Methods In the Japan Public Health Center‐based Prospective Study (baseline 1990 or 1993), we followed 25,391 never‐smoking women aged 40–69 years and without diabetes. Passive smoking was defined as having a husband who was a self‐reported smoker, and the exposure at a workplace (or public facilities) was self‐reported by women. The development of diabetes was identified in questionnaires administered at the 5‐year and 10‐year surveys. A pooled logistic regression model was used to assess the association between passive smoking and the development of diabetes with adjustment for age and possible confounders. Results Compared with women whose husbands had never smoked, women whose husband smoked ≥40 cigarettes/day had significantly higher odds of developing diabetes in an age‐adjusted model, but the association was attenuated in a multivariable model (odds ratio 1.34, 95% confidence interval 0.96–1.87). There was a dose–response trend between the number of cigarettes smoked by a husband and the odds of developing diabetes (P = 0.02). Women reporting daily passive smoking at a workplace (or public facilities) had higher odds of developing diabetes than women reporting no such exposure (odds ratio 1.23, 95% confidence interval 0.995–1.53). Conclusions Our results indicated a higher risk of diabetes among never‐smoking Japanese women with higher exposure to passive smoking from a spouse.

Background: Few studies examining the impact for women of employment status on health have considered domestic duties and responsibilities as well as household socioeconomic conditions. Moreover, to our knowledge, no studies have explored the influence of work-family conflict on the association between employment status and health. This research aimed to investigate the cross-sectional associations between employment status (regular employee, non-regular employee, or self-employed) with self-rated health among Japanese middle-aged working women. Methods: Self-report data were obtained from 21,450 working women aged 40–59 years enrolled in the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study) in 2011–2016. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for poor self-rated health (‘poor’ or ‘not very good’) by employment status. Sub-group analyses by household income and marital status, as well as mediation analysis for work-family conflict, were also conducted. Results: Adjusted ORs for the poor self-rated health of non-regular employees and self-employed workers were 0.90 (95% CI, 0.83–0.98) and 0.84 (95% CI, 0.75–0.94), respectively, compared with regular employees. The identified association of non-regular employment was explained by work-family conflict. Subgroup analysis indicated no statistically significant modifying effects by household income and marital status. Conclusion: Among middle-aged working Japanese women, employment status was associated with self-rated health; non-regular employees and self-employed workers were less likely to report poor self-rated health, compared with regular employees. Lowered OR of poor self-rated health among non-regular employees may be explained by their reduced work-family conflict.

Background: The association of alcohol drinking with bladder cancer risk remains unclear in East Asian populations. Aldehyde dehydrogenase 2 (ALDH2) enzyme oxidizes alcohol-metabolized carcinogenic acetaldehyde into acetate. It is well known that the inactive ALDH2 carriers, specific to East Asian populations, have an increased risk of several cancer types because of increased exposure to acetaldehyde after alcohol consumption. The aim of this study was to examine the association between alcohol drinking and bladder cancer risk using data from ten population-based prospective cohort studies in Japan, where approximately 40% of the population has inactive ALDH2 enzyme. Methods: We analyzed 340,497 Japanese participants with average follow-up of 13.4 years. The association between alcohol drinking and bladder cancer risk was evaluated using Cox regression models within each study, and random-effects models were used to estimate pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Results: During 4,729,071 person-years, 936 men and 325 women were newly diagnosed with bladder cancer. Our results showed no evidence of significant association between alcohol drinking and bladder cancer risk even among men who consumed alcohol of ≥69 g/week, with HR of 1.02 (95% CI, 0.79–1.33). The null result was observed consistently among women. Conclusions: Our findings do not support an association between alcohol drinking and bladder cancer risk in the Japanese, at least without consideration of the polymorphisms of alcohol-metabolizing enzymes.

Previous genome-wide association studies have identified risk loci for pancreatic cancer but were centered on individuals of European ancestry. Here the authors identify GP2 gene variants associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

Background: Some Okinawan vegetables have been reported to have anti-diabetic activity; however, no prospective cohort study has clarified whether consumption of Okinawan vegetables is associated with a risk of type 2 diabetes. This study aimed to determine the association between consumption of Okinawan vegetables and risk of type 2 diabetes through a large-scale, population-based, prospective study in Japan. Methods: We examined 10,732 participants (4,714 men and 6,018 women) aged 45–74 years who resided in Okinawa. Participants were asked to answer a 147-item food frequency questionnaire. We calculated the overall amount of Okinawan vegetables consumed and the amount of seven specific kinds of Okinawan vegetables consumed. The odds ratios (ORs) for self-reported type 2 diabetes during 5 years of follow-up were estimated via multivariate logistic regression analysis. Results: During the 5-year period, 216 new cases (123 men and 93 women) of type 2 diabetes were reported. Comparing the highest tertile to the lowest tertile of intake, the overall amount of Okinawan vegetables consumed was not associated with risk of type 2 diabetes in men (OR 1.22; 95% confidence interval [CI], 0.74–2.01, P-trend = 0.53) or in women (OR 0.96; 95% CI, 0.57–1.62, P-trend = 0.89). The consumption of seven specific kinds of Okinawan vegetables was also not associated with the risk of type 2 diabetes. Conclusions: The consumption of total Okinawan vegetables was not associated with the risk of type 2 diabetes.

Background: Evidence for primary prevention of chronic kidney disease (CKD) is insufficient. The population-based prospective Uonuma CKD cohort study aims to explore associations of lifestyle and other risk factors with CKD. We report here the study design and baseline profiles. Methods: All 67,322 residents aged ≥40 years in Minamiuonuma City, Uonuma City, and Yuzawa Town, Niigata Prefecture, Japan and 11,406 participants who attended local health-check examinations were targeted for baseline questionnaire and biochemical sampling, respectively. Information was gathered from 43,217 (64.2%) questionnaires and 8,052 (70.6%) biochemical samples; 6,945 participants consented to both questionnaire and biochemical sampling at baseline, conducted between fiscal years 2012 and 2015. Participants provided information regarding sociodemographic, lifestyle, and self-reported outcomes. Urine albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were measured. The primary outcome is CKD based on self-report and biochemical/clinical diagnosis. Results: Mean age of questionnaire respondents was 63.3 (standard deviation [SD], 12.5) years for men and 64.3 (SD, 13.3) years for women. Among participants who submitted urine samples, median ACR was 10.0 (interquartile range [IQR], 5.0–24.0) mg/g for men and 13.0 (IQR, 7.7–27.0) mg/g for women, and median eGFR was 73.6 mL/min/1.73 m2 (IQR, 63.5–84.5) for men and 73.5 mL/min/1.73 m2 (IQR, 64.4–83.5) for women. ACR 30 mg/g or more was found in 1,741 participants (21.7%) and eGFR

In breast cancer, genome-wide associations studies (GWAS) have highlighted loci associated with disease risk. Here, the authors perform a meta-analysis of GWAS data from Asian populations, discovering 31 potential new risk loci, 10 of which are validated in an independent disease cohort.

Abstract Background Due to concerns of carcinogenicity, it is necessary to assess long-term acrylamide exposure in individuals. Whether the available methods of estimating acrylamide intake can indicate long-term exposure remains unknown. We examined variations in the estimated dietary acrylamide intake of the Japanese population. Methods The study included 240 participants aged 40–74 years who were a part of the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT). Twelve-day dietary records (DRs) were collected over a one-year period, and food frequency questionnaires (FFQs) were collected twice during the year. Dietary acrylamide intake was estimated from an acrylamide content database. Within-individual variations and between-individual variations were calculated using the random effects model. A linear regression analysis was performed to identify foods with large between-individual variations. Results The ratios of within-individual variance to between-individual variation were 3.2 for men and 4.3 for women. Days of DRs required to estimate the usual individual intake within 20% of the true mean intake with 95% confidence were 60 days for men and 66 days for women. Coffee/cocoa, potato, and green tea contributed to between-individual variations, in that order, and seven foods contributed to 93% of the between-individual variation. Conclusions Estimating the acrylamide intake using DRs requires an extended data collection period to estimate the intragroup ranking and habitual intake of individuals. Long-term exposure assessments should be based on methods with less potential for measurement errors, such as the use of biomarkers.

Background: Lifestyle and life-environment factors have undergone drastic changes in Japan over the last few decades. Further, many molecular epidemiologic studies have reported that genetic, epigenetic, and other biomarker information may be useful in predicting individual disease risk. Methods: The Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT) was launched in 2011 to identify risk factors for lifestyle-related disease, elucidate factors that extend healthy life expectancy, and contribute toward personalized healthcare based on our more than 20 years’ experience with the JPHC Study. From 2011 through 2016, a baseline survey was conducted at 16 municipalities in seven prefectures across the country. A self-administered questionnaire was distributed to all registered residents aged 40–74, which mainly asked about lifestyle factors, such as socio-demographic situation, personal medical history, smoking, alcohol and dietary habits. We obtained informed consent from each participant to participate in this long follow-up study of at least 20 years, including consent to the potential use of their residence registry, medical records, medical fee receipts, care insurance etc., and to the provision of biospecimens (blood and urine), including genomic analysis. Results: As of December 31, 2016, we have established a population-based cohort of 115,385 persons (Response rate 44.1%), among whom 55,278 (47.9% of participants) have provided blood and urine samples. The participation rate was slightly higher among females and in the older age group. Conclusion: We have established a large-scale population-based cohort for next-generation epidemiological study in Japan.

Background: Few studies have investigated the effects of Okinawan vegetable consumption on the risk of incident stroke and coronary heart disease. This study aimed to examine associations of vegetable, fruit, and Okinawan vegetable consumption with risk of incident stroke and coronary heart disease in the Japanese population of Okinawa. Methods: The study design was a prospective cohort study. During 1995–1998, a validated food frequency questionnaire was administered in two study areas to 16,498 participants aged 45–74 years. In 217,467 person-years of follow-up until the end of 2012, a total of 839 stroke cases and 197 coronary heart disease cases were identified. Results: No statistically significant association between total Okinawan vegetable consumption and risk of stroke and coronary heart disease was obtained: the multivariable adjusted hazard ratios for the highest versus lowest tertile of consumption were 1.09 (95% confidence interval, 0.93–1.29; P for trend = 0.289) in model 2. Total vegetable and fruit and specific Okinawan vegetable consumption were also not statistically significantly associated with risk of cardiovascular outcomes. Conclusions: This study demonstrated that consumption of total vegetable and fruit, total Okinawan vegetables, and specific Okinawan vegetables in Japanese residents of Okinawa was not associated with risk of incident stroke and coronary heart disease.

Abstract Cigarette smoking and alcohol drinking are two major risk factors for esophageal cancer. Not all, but several of case‐control studies have indicated interaction between the two factors; however, no prospective study has validated this phenomenon to date. Therefore, the interaction between smoking and alcohol drinking is still open‐ended question. To answer this, we conducted a pooled analysis using large‐scale population‐based cohort studies in Japan. Male subjects from eight cohort studies were included. Cigarette smoking and alcohol drinking were both categorized categorically (never/ever), and in the three consumption levels of pack years and ethanol consumption/day. Effects of smoking and drinking in each study were estimated by Cox regression models. The study‐specific results were combined through meta‐analysis to obtain summary effects of hazard ratios (HRs) and measures of interactions at both additive and multiplicative scales. Population attributable fractions (PAFs) from smoking and drinking were obtained using distributions of exposures and fully adjusted HRs. In 162 826 male subjects, 954 esophageal cancer incidences were identified. HRs of ever smoking, ever drinking, and their combination were 2.92 (1.59‐5.36), 2.73 (1.78‐4.18), and 8.86 (4.82‐16.30), respectively. Interaction between cigarette smoking and alcohol drinking was significantly positive on the additive scale, but not significant on the multiplicative scale. The joint effect of smoking and drinking in three levels of evaluation showed a similar significant super‐additive interaction. PAFs from smoking, drinking, and their combination were 55.4%, 61.2%, and 81.4%, respectively. Cigarette smoking and alcohol drinking had a significant positive additive interaction for esophageal cancer risk.

Background. Gastric cancer (GC) is the fifth most common type of cancer and the fourth most common cause of cancer-related mortality. Although the risk of GC and peptic ulcer disease (PUD) is known to be increased by H. pylori infection, evidence regarding the direct relationship between PUD and GC across ethnicities is inconclusive. Therefore, we investigated the association between PUD and GC in the Stomach cancer Pooling (StoP) consortium. Methods. History of peptic ulcer disease was collected using a structured questionnaire in 11 studies in the StoP consortium, including 4106 GC cases and 6922 controls. The two-stage individual-participant data meta-analysis approach was adopted to generate a priori. Unconditional logistic regression and Firth’s penalized maximum likelihood estimator were used to calculate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between gastric ulcer (GU)/duodenal ulcer (DU) and risk of GC. Results. History of GU and DU was thoroughly reported and used in association analysis, respectively, by 487 cases (12.5%) and 276 controls (4.1%), and 253 cases (7.8%) and 318 controls (6.0%). We found that GU was associated with an increased risk of GC (OR = 3.04, 95% CI: 2.07–4.49). No association between DU and GC risk was observed (OR = 1.03, 95% CI: 0.77–1.39). Conclusions. In the pooled analysis of 11 case–control studies in a large consortium (i.e., the Stomach cancer Pooling (StoP) consortium), we found a positive association between GU and risk of GC and no association between DU and GC risk.

Background: Dietary components are known to affect chronic low-grade inflammation status. The dietary inflammatory index (DII®) was developed to measure the potential impact of a diet on an individual's inflammatory status, and it has been validated mainly in Western countries.Objective: This study aimed to examine the validity of the energy-adjusted DII (E-DIITM) using high-sensitivity C-reactive protein (hs-CRP) concentration in Japanese men and women.Methods: In total, 6,474 volunteers from a cancer-screening program (3,825 men and 2,649 women) completed a food frequency questionnaire (FFQ) and their hs-CRP concentrations were evaluated. E-DII scores were calculated on the basis of 30 food parameters derived from the FFQ. Higher E-DII scores reflect a greater pro-inflammatory potential of the diet. The associations between E-DII quartiles and hs-CRP concentration were assessed using regression models adjusted for age, body mass index, smoking status, and amount of physical activity.Results: Mean E-DII in men and women was + 0.62 ± 1.93 and −1.01 ± 2.25, respectively. The proportion of men and women who had hs-CRP concentration >3 mg/L was 4.7 and 3.1%, respectively. A significant positive association was observed between E-DII score and hs-CRP concentration in men; geometric mean of hs-CRP concentration in the lowest and highest E-DII quartiles was 0.56 mg/L and 0.67 mg/L (Ptrend < 0.01), respectively. The odds ratio (95% confidence interval) of having an elevated hs-CRP concentration (>3 mg/L) was 1.72 (1.10–2.67) in the highest E-DII quartile (Ptrend = 0.03) in men. However, no association was observed between E-DII score and hs-CRP concentration in women, except in those not taking prescription medications.Conclusions: DII was associated with inflammation status in Japanese men, but the association was limited in Japanese women.

Background: While tall stature has been linked to an increase in the risk of colorectal cancer (CRC), its association with cancer in the colorectum and its subsites remains unclear among Asians. Methods: We conducted a pooled analysis of 10 population-based cohort studies among adults in Japan. Each study estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC incidence associated with adult height were estimated using Cox proportional hazards regression with adjustment of the same set of covariates were then pooled to estimate summary HRs incidence using random-effect models. Results: We identified 9,470 CRC incidences among 390,063 participants during 5,672,930 person-years of follow-up. Men and women with tall stature had a higher risk of CRC and colon cancer. HRs for CRC, colon cancer, and distal colon cancer for the highest versus lowest height categories were 1.23 (95% CI, 1.07-1.40), 1.22 (95% CI, 1.09-1.36), and 1.27 (95% CI, 1.08-1.49), respectively, in men and 1.21 (95% CI, 1.09-1.35), 1.23 (95% CI, 1.08-1.40), and 1.35 (95% CI, 1.003-1.81), respectively, in women. The association with proximal colon cancer and rectal cancer was less evident in both sexes. Conclusion: This pooled analysis confirms the link between tall stature and a higher risk of CRC and colon cancer (especially distal colon) among the Japanese and adds evidence to support the use of adult height to identify those at a higher risk of CRC. [ABSTRACT FROM AUTHOR]

Thousands of genetic loci are known to associate with human height, but these are mainly based on studies in European ancestry populations. Here, Akiyama et al. construct a genotype reference panel for the Japanese population followed by GWAS and report 573 height associated variants in 191,787 Japanese.

More than 170 genetic loci have been linked to prostate cancer risk, primarily based on genome-wide association studies (GWAS) in European population. Here, the authors performed a GWAS on a Japanese cohort of prostate cancer patients, finding 12 new susceptibility loci, and identifying a polygenic risk for Japanese prostate cancer.

Background: The association of body mass index (BMI) with risks of ischemic stroke subtypes have not been established. Methods: Cumulative average BMI was calculated using self-reported body weight and height obtained from baseline (Cohort I in 1990, and Cohort II from 1993–1994) and 5- and 10-year questionnaire surveys of Japan Public Health Center-based prospective (JPHC) study. A total of 42,343 men and 46,413 women aged 40–69 years were followed-up for the incidence of lacunar, large-artery occlusive, and cardioembolic strokes. A sub-distribution hazard model was used to estimate sub-distribution hazard ratios (SHRs) and the 95% confidence intervals (CIs). Results: During a median of 20.0 years of follow-up, we documented 809 and 481 lacunar, 395 and 218 large-artery occlusive, and 568 and 298 cardioembolic strokes in men and women, respectively. After adjustment for baseline age, updated smoking, alcohol consumption, leisure-time physical activity, and histories of hypertension, dyslipidemia, and diabetes mellitus, cumulative average BMI was positively linearly associated with lacunar (trend P = 0.007), large-artery occlusive (trend P = 0.002), and cardioembolic (trend P < 0.001) strokes in men, and with lacunar (trend P < 0.001) and large-artery occlusive (trend P = 0.003) strokes in women. There were approximately two-fold excess risk of cardioembolic stroke in both sexes and of lacunar and large-artery occlusive strokes in women for cumulative average BMI ≥30 kg/m2 compared to BMI 23–

Background: Smoking and alcohol are established risk factors for several types of cancer, but the effects on biliary cancers, comprising biliary tract cancer (BTC) and intrahepatic bile duct cancer (IHBDC), have been inconclusive. Methods: In this population-based prospective cohort study in Japan, we investigated the association of smoking and alcohol consumption with the risks of BTC and its subtypes and IHBDC incidence in men and women. Furthermore, the association of smoking stratified by drinking status was investigated. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model. Results: A total of 48,367 men and 54,776 women aged 40–69 years were enrolled from 1990 through 1994 and followed up for 846,417 person-years in men and 1,021,330 person-years in women until 2012, during which 246 BTC and 80 IHBDC male cases and 227 BTC and 60 IHBDC female cases were identified. In men, smoking was significantly associated with an increased risk of IHBDC (HR 2.25; 95% CI, 1.19–4.25 for current smokers with ≥30 pack-years compared with non-smokers), and the risk was enhanced among regular drinkers compared with non/occasional-drinkers (HR 3.48; 95% CI, 1.41–8.61). A non-significant increase of IHBDC risk associated with alcohol was observed. Neither smoking nor alcohol consumption was associated with BTC risk. In women, the association of smoking and alcohol consumption with IHBDC and BTC was unclear because current smokers and regular drinkers were very few. Conclusion: Our findings suggest that smoking increases IHBDC risk in men, especially among regular drinkers.

Abstract Background Acid-base imbalance might promote the progression of chronic kidney disease (CKD), but whether nutrient-derived dietary acid load increases the risk of albuminuria or even high normoalbuminuria is unclear. Methods A Japanese cohort comprising 3250 men and 3434 women aged 40–97 years with urine albumin-to-creatinine ratio (ACR)

Abstract Aims/Introduction Menstrual and reproductive factors, including age at menarche, parity and breast‐feeding, have been linked to type 2 diabetes risk. We prospectively investigated the association between these factors and type 2 diabetes risk in a large Japanese cohort. Materials and Methods Participants were 37,511 women aged 45–75 years who participated in the baseline (1990–1993), second (1995–1998) and third surveys (2000–2003) of the Japan Public Health Center‐based Prospective Study, and who had no history of diabetes at the second survey. Menstrual and reproductive history was ascertained using questionnaires at the baseline and second surveys. Odds ratios of self‐reported, physician‐diagnosed type 2 diabetes over the 5‐year period from the second survey were estimated using logistic regression. Results At the third survey, 513 new cases of type 2 diabetes were self‐reported. The odds ratios of type 2 diabetes tended to increase with the number of parity, after adjustment for covariates other than body mass index (P for trend = 0.029). The multivariable‐adjusted odds ratios of type 2 diabetes for women with three or more births was 1.56 (95% confidence interval 0.96–2.53) compared with those who were nulliparous. The association between parity and type 2 diabetes risk was attenuated after additional adjustment for body mass index (P for trend = 0.12). No factors other than parity were significantly associated with type 2 diabetes risk. Conclusions Higher parity might be associated with an increased risk of type 2 diabetes among Japanese women, partly through increasing bodyweight.

Background: To update the findings of relative risk associated with smoking for all-cause mortality and that for lung cancer by considering longitudinal changes in smoking status during follow-up. Methods: Data from the JPHC study of 98,747 middle-aged Japanese adults, which started in 1990–1993, were analyzed. The information on smoking status was obtained from three questionnaire surveys (baseline, the 5th year, and the 10th year after the start of follow-up). A Poisson regression model was used to investigate the impact of smoking on mortality from all causes and lung cancer using two approaches. Model 1 used information only from baseline, while model 2 used the updated smoking status from all three surveys. Results: During the 15-year follow-up, 10,702 all-cause deaths (including 870 lung cancer cases) were identified. We compared the results obtained from two models. The relative risks associated with former smokers versus never smokers were 1.42 (95% confidence interval [CI], 1.31–1.54) among men and 1.46 (95% CI, 1.23–1.73) among women for all-cause mortality and 2.98 (95% CI, 2.09–4.24) among men and 1.83 (95% CI, 0.92–3.64) among women for lung cancer mortality, as determined using model 2. All of these were higher than the relative risks obtained from model 1. In addition, former smokers who had quit smoking due to disease during follow-up had a higher mortality risk than continuous smokers did in this study. Conclusions: The relative risks of all-cause mortality and mortality due to lung cancer among former smokers be higher than previously documented based on updated smoking status data from repeated surveys.

Background: Inconsistent findings have been reported regarding the relationship between dietary iron intake and the risk of gastric cancer (GC). Methods: We pooled data from 11 case-control studies from the Stomach Cancer Pooling (StoP) Project. Total dietary iron intake was derived from food frequency questionnaires combined with national nutritional tables. We derived the odds ratios (ORs) and 95% confidence intervals (CIs) for quartiles of dietary iron through multivariable unconditional logistic regression models. Secondary analyses stratified by sex, smoking status, caloric intake, anatomical subsite and histological type were performed. Results: Among 4658 cases and 12247 controls, dietary iron intake was inversely associated with GC (per quartile OR 0.88; 95% CI: 0.83–0.93). Results were similar between cardia (OR = 0.85, 95% CI = 0.77–0.94) and non-cardia GC (OR = 0.87, 95% CI = 0.81–0.94), and for diffuse (OR = 0.79, 95% CI = 0.69–0.89) and intestinal type (OR = 0.88, 95% CI = 0.79–0.98). Iron intake exerted an independent effect from that of smoking and salt intake. Additional adjustment by meat and fruit/vegetable intake did not alter the results. Conclusions: Dietary iron is inversely related to GC, with no difference by subsite or histological type. While the results should be interpreted with caution, they provide evidence against a direct effect of iron in gastric carcinogenesis.

Using Food Frequency Questionnaires (FFQs) to compare dietary references for screening has been in high demand. However, FFQs have been widely used for ranking individuals in a population based on their dietary intake. We determined the validity of sodium (salt equivalent) intake, potassium intake, and sodium-to-potassium (Na/K) ratio obtained using the FFQ for identifying individuals who deviated from the dietary reference intakes (DRIs) measured using multiple 24-h urinary excretion measurements or 12-day weighed food records (WFR). This study included 235 middle-aged subjects. The correlation coefficients (CCs) between the FFQ and WFR estimates were mostly moderate (0.24–0.54); the CCs between the FFQ and 24-h urinary excretion measurements were low or moderate (0.26–0.38). Values of area under the receiver-operating curve (AUC) at the point of DRIs for salt equivalent or potassium were >0.7 with the WFR as the reference standard and 0.60–0.76 with the 24-h urinary excretion as the reference standard. Using both standard measures, the AUC for the Na/K ratio was

Background: Acrylamide, a probable carcinogen to humans, forms during high temperature cooking. Dietary exposure to acrylamide among the Japanese population is unknown. We aimed to establish and validate a method to assess acrylamide exposure among the Japanese population using a food frequency questionnaire (FFQ) from the Japan Public Health Center-based prospective study. Methods: Validation studies for the FFQ were conducted in 1994 (Cohort I, n = 215) and 1996 (Cohort II, n = 350). The 28-day dietary records (DRs) were collected over 1 year. The FFQ was distributed before and after DR collection. Data for acrylamide exposure were based on reported measurements in Japan, and calculations considered the cooking process for specific vegetables in a home setting. Spearman’s rank correlation and weighted kappa coefficients were calculated from energy-adjusted data. Results: Mean acrylamide intake levels estimated from DRs for Cohorts I and II were 6.78 (standard deviation [SD], 3.89) µg/day and 7.25 (SD, 3.33) µg/day, and corresponding levels estimated from the FFQ were 7.03 (SD, 4.30) µg/day and 7.14 (SD, 3.38) µg/day, respectively. Deattenuated correlation coefficients for men and women were 0.54 and 0.48 in Cohort I and 0.40 and 0.37 in Cohort II, respectively. Weighted kappa coefficients were over 0.80 in all cases. The main contributing food groups from DRs were beverages, confectioneries, vegetables, potatoes and starches, and cereals. Conclusions: High kappa values validate the use of FFQ in epidemiological studies. The marked contribution of cooked vegetables indicates the importance of considering household cooking methods in assessing acrylamide intake levels in the Japanese population.

Background: High dietary non-enzymatic antioxidant capacity (NEAC) has been inversely related to the incidence of degenerative diseases. However, few studies have investigated the validity and reproducibility of dietary NEAC estimated from a food frequency questionnaire (FFQ). We assessed the validity and reproducibility of FFQ-based dietary NEAC against a dietary record (DR). Methods: Participants were 244 men and 253 women who completed a 28-day DR and FFQs. NEAC for each food item was estimated according to available databases of antioxidant capacity, as measured by ferric reducing-antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and total radical-trapping antioxidant parameter (TRAP). Using Spearman’s rank correlation coefficients (CCs), we assessed the validity for dietary NEACs from a 28-day DR and a FFQ, and the reproducibility for them from two FFQs administered at a 1-year interval. Additionally, joint classification and the Bland-Altman method were applied to assess agreement between the two methods. Results: Regarding validation, deattenuated CCs for the energy-adjusted overall dietary NEACs between FFQ and DR for FRAP, ORAC, and TRAP were 0.52, 0.54, and 0.52, respectively, for all subjects. Extreme miscategorization rates by joint classification analysis were 2% for FRAP and ORAC and 1% for TRAP. Regarding reproducibility, CCs between the energy-adjusted dietary NEACs from two FFQs were 0.64 for FRAP and 0.65 for ORAC and TRAP. Conclusion: The validity and reproducibility of dietary NEAC of total food from the FFQ were moderate. Estimations of dietary NEAC using FFQ would be useful in studying disease relationships by categorizing habitual dietary NEAC.

We examine the validity and reproducibility of a food frequency questionnaire (FFQ) in a subsample of participants in the Japan Public Health Center-based Prospective Cohort Study using a database of polyphenol-containing foods commonly consumed in the Japanese population. Participants of the validation study were recruited from two different cohorts. In Cohort I, 215 participants completed a 28-d dietary record (DR) and the FFQ, and in Cohort II, 350 participants completed DRs and the FFQ. The total polyphenol intake estimated from the 28-d DR and FFQ were log-transformed and adjusted for energy intake by the residual method. Spearman correlation coefficients (CCs) between estimates from the FFQ and 28-d DR as well as two FFQs administered at a 1-year interval were computed. Median intakes of dietary polyphenols calculated from the DRs were 1172 mg/d for men and 1024 mg/d for women in Cohort I, and 1061 mg/d for men and 942 mg/d for women in Cohort II. The de-attenuated CCs for polyphenol intake between the DR and FFQ were 0⋅47 for men and 0⋅37 for women in Cohort I and 0⋅44 for men and 0⋅50 for women in Cohort II. Non-alcoholic beverages were the main contributor to total polyphenol intake in both men and women, accounting for 50 % of total polyphenol intake regardless of cohort and gender, followed by alcoholic beverages and seasoning and spices in men, and seasoning and spices, fruits and other vegetables in women. The present study showed that this FFQ had moderate validity and reproducibility and is suitable for use in future epidemiological studies.

The Japan Public Health Center-based prospective study- physical activity questionnaire (JPHC-PAQ) was originally developed and validated for total physical activity (total PA). However, it is uncertain whether JPHC-PAQ could also estimate intensity-specific physical activity. The present study aims to evaluate the validity and reliability of intensity-specific physical activity by the JPHC-PAQ against 24-hour activity records (24 h-R). One-hundred and ten participants were chosen from those who had enrolled in the JPHC cohort. Time spent for total PA and intensity-specific physical activity, i.e. moderate (MPA), vigorous (VPA) and moderate-to-vigorous physical activity (MVPA) was estimated by JPHC-PAQ. In addition, the volume of PA was calculated by time of each activity multiplied by intensity of activity. For validity assessment, estimated physical activities were compared with 24 h-R. For reliability evaluation, a retest was conducted 3–6 months after the first survey was answered. Moderately strong correlation between JPHC-PAQ and 24 h-R was observed for total PA estimations (Spearman’s rho = 0.672). In addition, moderate correlations were found for MPA (activity time: rho = 0.345, activity volume: rho = 0.300) and MVPA (activity time: rho = 0.563, activity volume: rho = 0.672). Whereas, little association was found for VPA time and volume. As for reliability, moderately strong correlation was found for both total and intensity-specific physical activity in the test–retest (rho = 0.482–0.745). In addition to total PA, the JPHC-PAQ showed acceptable validity and reliability for intensity-specific physical activity, especially in estimating MVPA and MPA.

Although their functional outcomes remain largely unknown, single nucleotide polymorphisms (SNPs) in the fat mass and obesity-associated gene (FTO) may interact with adipokines, especially leptin and adiponectin, to modify the risk of colorectal cancer. We conducted a prospective study of 375 colorectal cancer cases and 750 matched controls to examine the effects of SNPs in the FTO, either alone or in interaction with pre-diagnostic plasma adipokine levels. Using a conditional logistic regression model, we obtained odds ratios (ORs) and their 95% confidence intervals (CIs) of colorectal cancer. Seven SNPs in strong linkage disequilibrium demonstrated a similarly positive association with colorectal cancer, and most evidently for rs1558902, rs8050136, rs3751812, and rs9939609 (Ptrend = 0.02). Of interest, we observed a statistically significant interaction of rs8050136 with plasma total adiponectin levels (Pinteraction = 0.03). Compared to non-carriers in the lowest quintile of plasma total adiponectin, A allele carriers in the same quintile showed a considerably elevated risk of colorectal cancer, with a body mass index-adjusted OR of 2.54 (95% CI, 1.36-4.75). This investigation of the interaction between SNPs in the FTO and pre-diagnostic plasma adipokine levels has revealed the importance of both genetic and hormonal factors associated with adiposity in colorectal carcinogenesis.

PurposeWe examined the association between meat intake and mortality due to all-cause and major causes of death using a population-based cohort study in Japan.Methods87,507 Japanese aged between 45 and 74 years old at 5-year follow-up study were followed for 14.0 years on average. Associations between meat intake and mortality risk were assessed using a Cox proportional hazards model.ResultsA heavy intake of total meat was associated with a higher risk of all-cause mortality relative to the lowest quartile intake in men (Q4: HR,1.18; 95%CIs, 1.06-1.31). A higher intake of total meat was associated with a lower risk of stroke mortality in women (Q2: HR, 0.70; 95%CIs, 0.51-0.94, Q3: HR, 0.68; 95%CIs, 0.50-0.95, Q4: HR, 0.66; 95%CIs, 0.44-0.99). A heavy intake of red meat was also associated with all-cause mortality (Q4: HR, 1.13; 95%CIs, 1.02-1.26) and heart disease mortality (Q4: HR, 1.51; 95%CIs, 1.11-2.06) in men but not in women. Heavy intake of chicken was inversely associated with cancer mortality in men.ConclusionsHeavy intakes of total and red meat were associated with an increase in all-cause and heart disease mortality in men, while total meat intake was associated with a lower risk of stroke mortality in women.

Abstract Background Age-related musculoskeletal diseases are becoming increasingly burdensome in terms of both individual quality of life and medical cost. We intended to establish a large population-based cohort study to determine environmental, lifestyle, and genetic risk factors of musculoskeletal and other age-related diseases, and to clarify the association between vitamin D status and such diseases. Methods We targeted 34,802 residents aged 40–74 years living in areas of northern Niigata Prefecture, including Sekikawa Village, Awashimaura Village, and Murakami City (Murakami region). The baseline questionnaire survey, conducted between 2011 and 2013, queried respondents on their lifestyle and environmental factors (predictors), and self-reported outcomes. Plasma 25-hydroxyvitamin D (25[OH]D) concentration, an indicator of vitamin D status, was determined with the Liaison® 25OH Vitamin D Total Assay. The primary outcome of this study was osteoporotic fracture; other outcomes included age-related diseases including knee osteoarthritis, perception of chronic pain, dementia, and long-term care insurance use. Mean ages of men and women were 59.2 (SD = 9.3, N = 6907) and 59.0 (SD = 9.3, N = 7457) years, respectively. From the blood samples provided by 3710 men and 4787 women, mean 25(OH)D concentrations were 56.5 (SD = 18.4) nmol/L (22.6 ng/mL) and 45.4 (SD = 16.5) nmol/L (18.2 ng/mL), respectively. Discussion Follow-up surveys are planned every 5 years for 15 years, and incident cases of our targeted diseases will be followed at hospitals and clinics in and nearby the cohort area. We anticipate that we will be able to clarify the association between vitamin D status and multiple disease outcomes in a Japanese population.

Abstract Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer incidence in Western countries. However, few epidemiological studies have assessed the association between anthropometric factors, such as BMI, height, or weight, and thyroid cancer incidence in Asian populations. Using the population‐based Japan Public Health Center‐based prospective study database, we investigated the relationship between anthropometric factors and thyroid cancer incidence. Data on anthropometric factors were collected through a self‐administered questionnaire at baseline. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards model, and the exposure level was categorized into quintiles. A total of 49,062 men and 53,661 women enrolled between 1990 and 1994 were included in our analyses, and 191 cases (37 in men and 154 in women) of thyroid cancer were identified, with 1,695,702 person‐years of follow‐up until 2010. Compared with the male group with height ≤160 cm, HRs of the male groups with height 165–168 cm and ≥169 cm were 3.92 (95% CI; 1.33–11.55, P = 0.013) and 4.24 (95% CI; 1.32–13.61, P = 0.015), respectively, and the HR per 5‐cm increase in height was 1.12 (95% CI 1.06–1.18, P