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Background: We aimed to evaluate the validity of self-administered questionnaire surveys and face-to-face interview surveys for the detection of Helicobacter pylori eradication therapy. Methods: Participants were a cohort, aged 40–74 years, living in three different locations of Japan, who took part in the baseline survey (2011–2012) of the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT). Five years after the baseline survey, a questionnaire and interview survey were independently conducted to determine the history of Helicobacter pylori eradication treatment over the 5-year period. Prescription of Helicobacter pylori eradication medications in national insurance claims data from the baseline survey to the 5-year survey was used as a reference standard. Results: In total, 15,760 questionnaire surveys and 8,006 interview surveys were included in the analysis. There were 3,471 respondents to the questionnaire and 2,398 respondents to the interview who reported having received Helicobacter pylori eradication treatment within the past 5 years. Comparison of the questionnaire survey to national insurance claims data showed a sensitivity of 95.1% (2,213/2,328), specificity of 90.6% (12,174/13,432), positive predictive value of 63.8% (2,213/3,471), negative predictive value of 99.1% (12,174/12,289), and Cohen’s Kappa value of 0.71. Respective values of the interview survey were 94.4% (1,694/1,795), 88.7% (5,507/6,211), 70.6% (1,694/2,398), 98.2% (5,507/5,608), and 0.74. Conclusion: Both the questionnaire and the interview showed high sensitivity, high specificity, and good agreement with the insurance claim prescriptions data. Some participants may have received eradication treatment without going through the public insurance claim database, resulting in a low positive predictive value.

Background: The Japanese database of food composition was revised in 2020, during which both the number of food items and the number of food items measured for sugars, amino acids, and fatty acids were increased. We evaluated the validity of estimated intakes of sugars, amino acids and fatty acids using a long food frequency questionnaire (long-FFQ) among middle-aged and elderly Japanese. Methods: From 2012 to 2013, 240 men and women aged 40–74 years from five areas in the JPHC-NEXT protocol were asked to respond to the long-FFQ and provide a 12-day weighed food record (WFR) as reference. The long-FFQ, which included 172 food and beverage items and 11 seasonings, was compared with a 3-day WFR, completed during each distinct season, and validity was assessed using Spearman’s correlation coefficients. Results: Percentage differences based on the long-FFQ with the 12-day WFR in men and women varied from −84.4% to 419.6%, and from −75.8% to 623.1% for sugars, −17.5% to 3.8% and −5.8% to 19.6% for amino acids, and −58.5% to 78.8% and −43.4% to 129.3% for fatty acids, respectively. Median values of correlation coefficients for the long-FFQ in men and women were 0.52 and 0.42 for sugars, 0.38 and 0.37 for amino acids, and 0.42 and 0.42 for fatty acids, respectively. Conclusion: The long-FFQ provided reasonable validity in estimating the intakes of sugars, amino acids, and fatty acids in middle-aged and elderly Japanese. Although caution is warranted for some nutrients, these results may be used in future epidemiological studies.

Background: An association between birth weight and cardiovascular disease (CVD) in adulthood has been observed in many countries; however, only a few studies have been conducted in Asian populations. Methods: We used data from the baseline survey (2011–2016) of the Japan Public Health Center-based Prospective Study for the Next Generation Cohort, which included 114,105 participants aged 40–74 years. Adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were calculated from the prevalence of present and past histories of CVD and other lifestyle-related diseases, including hypertension, diabetes, hyperlipidemia, and gout, by birth weight, using Poisson regression. Results: The prevalence of CVD increased with lower birth weight, with the highest prevalence among those with birth weight under 1,500 grams (males 4.6%; females 1.7%) and the lowest one among those with birth weight at or over 4,000 g (males 3.7%: females 0.8%). Among 88,653 participants (41,156 males and 47,497 females) with complete data on possible confounders, birth weight under 1,500 g was associated with a higher prevalence of CVD (aPR 1.76; 95% CI, 1.37–2.26), hypertension (aPR 1.29; 95% CI, 1.17–1.42), and diabetes (aPR 1.53; 95% CI, 1.26–1.86) when a birth weight of 3,000–3,999 grams was used as the reference. Weaker associations were observed for birth weight of 1,500–2,499 grams and 2,500–2,999 grams, while no significant associations were observed for birth weight at or over 4,000 grams. The association between birth weight and the prevalence of hyperlipidemia was less profound, and no significant association was observed between birth weight and gout. Conclusion: Lower birth weight was associated with a higher prevalence of CVD, hypertension, and diabetes in the Japanese population.

Background: Associations of major risk factors for stroke with total and each type of stroke, as well as subtypes of ischemic stroke, and their population attributable fractions had not been examined comprehensively. Methods: Participants of the Japan Public Health Center-based prospective (JPHC) Study Cohort II without histories of cardiovascular disease and cancer (n = 14,797) were followed from 1993 through 2012. Associations of current smoking, hypertension, diabetes, overweight (body mass index ≥25 kg/m2), non-high-density lipoprotein cholesterol (non-HDLC) categories, low HDLC (

Abstract Accurate measurement of sodium intake in the diet is challenging, and epidemiological studies can be hampered by the attenuation of associations due to measurement error in sodium intake. A prediction formula for habitual 24-h urine sodium excretion and sodium-to-potassium ratio might lead to more reliable conclusions. Five 24-h urinary samples and two Food Frequency Questionnaires (FFQs) were conducted among 244 Japanese participants aged 35–80 years. We conducted multivariate linear regression analysis with urinary excretion as dependent variables and eating behaviour and food frequency as independent variables. Empirical weights of sodium excretion and sodium-to-potassium ratio were extracted. Preliminary validity was also assessed by randomly dividing the subjects into development and validation groups based on the correlation coefficient between estimates by the prediction formula and urinary excretion. Taste preference, soy sauce use at the table, frequency of pickled vegetables intake and number of bowls of miso soup were extracted as determinants of sodium excretion. Correlation coefficients between the estimates and urinary excretion for men and women were 0.42 and 0.43, respectively, for sodium and 0.49 and 0.50, respectively, for sodium-to-potassium ratio. This prediction formula may provide more accurate estimation of sodium intake and sodium-to-potassium ratio than the food composition approach.

Background: This study aimed to develop models to predict the 5-year incidence of type 2 diabetes mellitus (T2DM) in a Japanese population and validate them externally in an independent Japanese population. Methods: Data from 10,986 participants (aged 46–75 years) in the development cohort of the Japan Public Health Center-based Prospective Diabetes Study and 11,345 participants (aged 46–75 years) in the validation cohort of the Japan Epidemiology Collaboration on Occupational Health Study were used to develop and validate the risk scores in logistic regression models. Results: We considered non-invasive (sex, body mass index, family history of diabetes mellitus, and diastolic blood pressure) and invasive (glycated hemoglobin [HbA1c] and fasting plasma glucose [FPG]) predictors to predict the 5-year probability of incident diabetes. The area under the receiver operating characteristic curve was 0.643 for the non-invasive risk model, 0.786 for the invasive risk model with HbA1c but not FPG, and 0.845 for the invasive risk model with HbA1c and FPG. The optimism for the performance of all models was small by internal validation. In the internal-external cross-validation, these models tended to show similar discriminative ability across different areas. The discriminative ability of each model was confirmed using external validation datasets. The invasive risk model with only HbA1c was well-calibrated in the validation cohort. Conclusion: Our invasive risk models are expected to discriminate between high- and low-risk individuals with T2DM in a Japanese population.

Objective This population-based, cross-sectional study was performed to investigate the relationship between a history of glaucoma and subjective happiness.Methods and analysis We conducted a cross-sectional questionnaire-based survey of 92 397 Japanese men and women aged 40–74 who participated in the Japan Public Health Center-based Prospective Study for the Next Generation study. A multivariable logistic regression model was used to estimate the ORs of glaucoma associated with subjective happiness and their two-sided 95% CIs.Results Among 40 727 men and 51 670 women, 1733 participants (635 men, 1098 women) had a history of glaucoma. The odds of unhappiness in male participants with a history of glaucoma were higher (OR 1.26; 95% CI 1.05 to 1.51) than in female participants (OR 1.05; 95% CI 0.90 to 1.23). In a subgroup analysis stratified by age, among participants with a history of glaucoma, males in the younger group (40–59 years) showed the most robust association with unhappiness (OR 1.40; 95% CI 1.04 to 1.88).Conclusions These findings suggest that a history of glaucoma is related with subjective unhappiness, especially in men.

Background: Many epidemiological studies have investigated dietary intake of antioxidant vitamins in relation to prostate cancer risk in Western countries, but the results are inconsistent. However, few studies have reported this relationship in Asian countries. Methods: We investigated the association between intake of vitamins, including lycopene, α-carotene, β-carotene, vitamin C, vitamin E, with prostate cancer risk in the Japan Public Health Center-based Prospective (JPHC) study. 40,720 men without history of cancer finished the food frequency questionnaire (FFQ) and were included in the study. Hazard ratios (HRs) and 95% confidence intervals (CIs) of prostate cancer risk were calculated according to the quintiles of energy-adjusted intake of vitamins using Cox models. Results: After an average of 15.2 years (617,599 person-years in total) of follow-up, 1,386 cases of prostate cancer were identified, including 944 localized cases and 340 advanced cases. No associations were observed in consumption of antioxidant vitamins, including α-carotene, β-carotene, vitamin C, and vitamin E, and prostate cancer risk. Although higher lycopene intake was associated with increased risk of prostate cancer (highest vs lowest quintile, HR 1.24; 95% CI, 1.04–1.47; P for trend = 0.01), there was a null association of lycopene intake with risk of prostate cancer detected by subjective symptoms (HR 1.12; 95% CI, 0.79–1.58; P for trend = 0.11). Conclusion: Our study suggested no association between antioxidant intake of vitamins and prostate cancer risk.

Abstract Several studies have investigated the association between the use of anti-cholesterol drugs and cancer risks, of which results have been inconsistent. This study included 67,768 participants from the Japan Public Health Center-based Prospective Study. The data on anti-cholesterol drug use was collected using three questionnaires of the survey conducted every five years. We divided the participants into three groups according to the duration of the anti-cholesterol drug use. Multivariable-adjusted Cox proportional hazard regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). During the 893,009 person-years of follow-up from the 10-year follow-up survey, 8,775 participants (5,387 men and 3,388 women) were newly diagnosed with cancers. The duration of anti-cholesterol drug use was significantly associated with a decreased risk of liver cancer (HR:0.26, 95% CI 0.11–0.64 in > 5 y group) and with an increased risk of pancreatic cancer (HR:1.59, 95% CI 1.03–2.47 in > 5 y group). Moreover, a different trend was observed between men and women in the association with the risk of lung cancer. This study suggested that long-term use of anti-cholesterol drugs may have associations with a decreased incidence of liver cancer and with an increased incidence of pancreatic cancers.

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 Background The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. Methods This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. Results Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66–1.13] compared to 0.60 [0.49–0.73], 0.46 [0.38–0.56] and 0.62 [0.51–0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14–1.84] compared to 1.25 [0.99–1.58], 1.06 [0.85–1.32] and 0.86 [0.69–1.08]) and alcohol consumption (1.22 [1.01–1.48] compared to 1.10 [0.90–1.33], 1.15 [0.96–1.38], and 1.07 [0.91–1.26]). Conclusion We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.

Abstract Background Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. Methods A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow‐up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random‐effects meta‐analyses. Results Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06–1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07–1.60 vs 1.12, 1.01–1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02–1.28 vs 1.17, 0.77–1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02–1.46 vs 1.00, 0.62–1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77–5.86), and decreased with time (nonlinear p

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

Abstract Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values

Background: The association between hobby engagement and risk of dementia reported from a short-term follow-up study for individuals aged ≥65 years may be susceptible to reverse causation. We examined the association between hobby engagement in age of 40–69 years and risk of dementia in a long-term follow-up study among Japanese, including individuals in mid-life, when the majority of individuals have normal cognitive function. Methods: A total of 22,377 individuals aged 40–69 years completed a self-administered questionnaire in 1993–1994. The participants answered whether they had hobbies according to the three following responses: having no hobbies, having a hobby, and having many hobbies. Follow-up for incident disabling dementia was conducted with long-term care insurance data from 2006 to 2016. Results: During a median of 11.0 years of follow-up, 3,095 participants developed disabling dementia. Adjusting for the demographic, behavioral, and psychosocial factors, the multivariable hazard ratios of incident disabling dementia compared with “having no hobbies” were 0.82 (95% confidence interval [CI], 0.75–0.89) for “having a hobby” and 0.78 (95% CI, 0.67–0.91) for “having many hobbies”. The inverse association was similarly observed in both middle (40–64 years) and older ages (65–69 years). For disabling dementia subtypes, hobby engagement was inversely associated with the risk of dementia without a history of stroke (probably non-vascular type dementia), but not with that of post-stroke dementia (probably vascular type dementia). Conclusion: Hobby engagement in both mid-life and late life was associated with a lower risk of disabling dementia without a history of stroke.

Abstract Residents of Chikusei City, aged 40–74 years, underwent systemic and ophthalmological screening, and participants with diabetes were included in this analysis. Dietary intake was assessed using a food frequency questionnaire and calculated as a percentage of the total energy. The presence of diabetic retinopathy (DR) was defined as Early Treatment Diabetic Retinopathy Study levels ≥ 20 in either eye. The association between dietary fatty acid intake and DR has been examined in a cross-sectional study. Among the 647 diabetic participants, 100 had DR. The mean total fat and saturated fatty acid (SFA) intakes were 22.0% and 7.3% of the total energy intake, respectively. After adjusting for potential confounders, the highest quartiles of total fat and SFA intake were positively associated with the presence of DR compared with the lowest quartiles (odds ratios (95% confidence intervals), 2.61 (1.07–6.39), p for trend = 0.025, and 2.40 (1.12–5.17), p for trend = 0.013, respectively). No significant associations were found between DR prevalence and monounsaturated or unsaturated fatty acid intake. These results suggest that a high intake of fat and SFA may affect the development of DR, even in individuals whose total fat intake is generally much lower than that of Westerners.

Background: Recent innovations in information and communication technology have made it possible to assess diet using web-based methods; however, their applicability in the general population remains unclear. Hence, we aimed to examine the applicability of a web-based 24-hour dietary recall (24HR) tool to large-scale epidemiological studies by determining the sampling rate and characteristics of randomly selected participants from a Japanese cohort study. Methods: In total, 5,013 individuals were recruited from a cohort of 21,537 individuals, and 975 agreed to participate in this study. The participants selected either self-administered web-based dietary 24HR (self-administered 24HR) or interviewer-administered telephone-based 24HR (interviewer-administered 24HR) as the method for the dietary assessment and answered questions regarding the acceptability of the system. Results: The response rate of the 975 participants was 19.4%, corresponding to approximately 4.5% of the total study sample. About half of them chose the self-administered 24HR (46.9%). The median time required for the self-administered and interviewer-administered 24HR was 25 and 27 minutes, respectively. In the self-administered 24HR, older people, regardless of sex, tended to require a longer time, and approximately 60% of the participants rated the ease of use of the system as “somewhat difficult” or “difficult.” Conclusion: Characteristics of the participants in this study were not systemically different from those of the entire study sample. Improvements in the approach to entering cooking details and the dish name selection may be necessary for better acceptability in order to be accepted as a self-administered dietary recall tool.

Background: The number of people with cognitive impairment, including dementia, in the world is steadily increasing. Although the consumption of isoflavones and soy is associated with a reduced risk of cardiovascular disease, it might also be associated with cognitive impairment. The low number of studies investigating the association between soy/isoflavone intake and cognitive function warrant additional research. Methods: The Japan Public Health Center-based prospective (JPHC) Study is a large population-based cohort. Midlife dietary intake of soy and the isoflavone genistein was assessed on two occasions: in the years 1995 and 2000. In 2014–2015, 1,299 participants from Nagano prefecture completed a mental health screening. Of these, a total of 1,036 participants were included in analyses. Logistic regression was used to determine Odds Ratios (OR) and 95% Confidence Intervals (CI) for the association between midlife energy-adjusted genistein and soy food intake and cognitive impairment. Results: There were 392 cases of cognitive impairment (346 cases of MCI and 46 cases of dementia). Compared to the lowest dietary quartile of energy-adjusted genistein intake, the highest quartile was significantly associated with cognitive impairment (OR = 1.51; 95% CI, 1.02–2.24; P for trend = 0.03) in the final multivariable analysis. Conclusion: High midlife intake of the isoflavone genistein is associated with late-life cognitive impairment.

Abstract Objective: To assess dietary behaviours and related lifestyles according to the presence or absence of skipping breakfast. Design: We analysed the cross-sectional data from a baseline survey of a large-scale population-based cohort study in Japan conducted in 2011–2016. Participants provided information on dietary behaviours and lifestyles through a self-administered questionnaire. Skipping breakfast was defined as not eating breakfast at least once a week and was classified according to the frequency of skipping breakfast as 1–2, 3–4 or ≥5 times/week. Setting: Sixteen municipalities in seven prefectural areas across Japan under the Japan Public Health Centre-based prospective study for the Next Generation. Participants: 112 785 residents (51 952 males and 60 833 females) aged 40–74 years. Results: After adjustment for age, socio-demographic status, drinking status and smoking status, individuals who skipped breakfast at least once a week, compared with those who ate breakfast every day, were more likely to have adverse dietary behaviours such as frequent eating out (multivariable OR = 2·08, 95 % CI (1·96, 2·21) in males and 2·15, 95 % CI (1·99, 2·33) in females), frequent eating instant foods (1·89, 95 % CI (1·77, 2·01) in males and 1·72, 95 % CI (1·56, 1·89) in females). They had late bedtime (1·85, 95 % CI (1·75, 1·95) in males and 1·98, 95 % CI (1·86, 2·11) in females) and living alone (2·37, 95 % CI (2·17, 2·58) in males and 2·02, 95 % CI (1·83, 2·21) in females), using the logistic regression model. Conclusions: Both adult males and females who skipped breakfast were likely to eat out, to have a dietary habit of eating instant foods and have lifestyles such as late bedtime and living alone than those who ate breakfast.

Abstract Observational studies suggest that abnormal glucose metabolism and insulin resistance contribute to colorectal cancer; however, the causal association remains unknown, particularly in Asian populations. A two-sample Mendelian randomisation analysis was performed to determine the causal association between genetic variants associated with elevated fasting glucose, haemoglobin A1c (HbA1c), and fasting C-peptide and colorectal cancer risk. In the single nucleotide polymorphism (SNP)-exposure analysis, we meta-analysed study-level genome-wide associations of fasting glucose (~ 17,289 individuals), HbA1c (~ 52,802 individuals), and fasting C-peptide (1,666 individuals) levels from the Japanese Consortium of Genetic Epidemiology studies. The odds ratios of colorectal cancer were 1.01 (95% confidence interval [CI], 0.99–1.04, P = 0.34) for fasting glucose (per 1 mg/dL increment), 1.02 (95% CI, 0.60–1.73, P = 0.95) for HbA1c (per 1% increment), and 1.47 (95% CI, 0.97–2.24, P = 0.06) for fasting C-peptide (per 1 log increment). Sensitivity analyses, including Mendelian randomisation-Egger and weighted-median approaches, revealed no significant association between glycaemic characteristics and colorectal cancer (P > 0.20). In this study, genetically predicted glycaemic characteristics were not significantly related to colorectal cancer risk. The potential association between insulin resistance and colorectal cancer should be validated in further studies.

Background: Validation studies of diabetes definitions using nationwide healthcare databases are scarce. We evaluated the validity of diabetes definitions using disease codes and antidiabetic drug prescriptions in the Japanese Diagnosis Procedure Combination (DPC) data via medical chart review. Methods: We randomly selected 500 records among 15,334 patients who participated in the Japan Public Health Center-Based Prospective Study for the Next Generation in Yokote City and who had visited a general hospital in Akita between October 2011 and August 2018. Of the 500 patients, 98 were linked to DPC data; however, only 72 had sufficient information in the medical chart. Gold standard confirmation was performed by board-certified diabetologists. DPC-based diabetes definitions were based on the International Classification of Diseases, 10th Revision codes and antidiabetic prescriptions. Sensitivity, specificity, and the positive and negative predictive values (PPV and NPV, respectively) of DPC-based diabetes definitions were evaluated. Results: Of 72 patients, 23 were diagnosed with diabetes using chart review; 19 had a diabetes code, and 13 had both a diabetes code and antidiabetic prescriptions. The sensitivity, specificity, PPV, and NPV were 89.5% (95% confidence interval [CI], 66.9–98.7%), 96.2% (95% CI, 87.0–99.5%), 89.5% (95% CI, 66.9–98.7%), and 96.2% (95% CI, 87.0–99.5%), respectively, for (i) diabetes codes alone; 89.5% (95% CI, 66.9–98.7%), 94.3% (95% CI, 84.3–98.8%), 85.0% (95% CI, 62.1–96.8%), and 96.2% (95% CI, 86.8–99.5%) for (ii) diabetes codes and/or prescriptions; 68.4% (95% CI, 43.4–87.4%), 100% (95% CI, 93.3–100%), 100% (95% CI, 75.3–100%), and 89.8% (95% CI, 79.2–96.2%) for (iii) both diabetes codes and prescriptions. Conclusion: Our results suggest that DPC data can accurately identify diabetes among inpatients using (i) diabetes codes alone or (ii) diabetes codes and/or prescriptions.

Abstract INTRODUCTION Insufficient evidence exists on the sex‐specific associations of body mass index (BMI) and weight change through midlife with dementia incidence, especially in Asian populations. METHODS For 37,414 Japanese residents aged 40 to 59 years, BMIs at baseline (year 1990 or 1993) and 10‐year follow‐ups were obtained. Weight changes between baseline and 10‐year follow‐ups were determined. Disabling dementia incidence from 2006 to 2016 was ascertained using long‐term care insurance (LTCI) certifications. Hazard ratios (HRs) were computed. RESULTS Increased dementia risk was observed with obesity at baseline and with underweight at 10‐year follow‐ups. Weight loss after baseline was at greater risk than weight gain. No sex difference was observed. DISCUSSION In both sexes, obesity in midlife increased the risk of developing dementia with increasing impacts of weight loss after midlife. A healthy body weight throughout adulthood is beneficial for dementia prevention. Highlights Obesity in midlife is a risk factor for incident dementia. Weight loss is a bigger risk factor than weight gain in later midlife. Association of BMI and weight change in midlife with dementia does not vary by sex.

Background: The place of death and related factor, such as diseases, symptoms, family burden, and cost, has been examined, but social background and lifestyle were not considered in most studies. Here, we assessed factors that are associated with the place of death using the largest cohort study in Japan. Methods: A total of 17,781 deaths from the cohort study were assessed. The study database was created from the Japan Public Health Center-based Prospective Study (JPHC Study), in which demographic data were collected from Japanese Vital Statistics. Adjusted odds ratios for home death were calculated using logistic regression. Results: Multivariate analysis adjusted for various factors showed that unmarried status (odds ratio [OR] 2.4; 95% confidence interval [CI], 2.0–2.9), unemployed male (OR 1.3; 95% CI, 1.1–1.5), and high drinking level in male (OR 1.3; 95% CI, 1.1–1.6) were associated with home death. Regarding the cause of death, cardiovascular disease (OR 3.3; 95% CI, 2.9–3.8), cerebrovascular disease (OR 1.9; 95% CI, 1.6–2.2), and external factors (OR 4.1; 95% CI, 3.5–4.8) were significantly associated with home death, compared with cancer. The risk of death at home was significantly higher among unmarried subjects stratified by cause of death (cardiovascular disease: OR 3.2; 95% CI, 2.2–4.7; cerebrovascular disease: OR :5.1; 95% CI, 2.9–9.1; respiratory disease: OR 3.4; 95% CI, 1.6–7.6; and external factors: OR 2.3; 95% CI, 1.4–3.7), but for cancer, the risk of death at home tended to be higher among married participants. Conclusion: This study found that various factors are associated with home death using the largest cohort study in Japan. There is a high possibility of home deaths in people with fewer social connections and in those with diseases leading to sudden death.

Abstract Background The repeated global pandemic of the new virus has led to interest in the possibility of severe pneumonia among cancer patients and survivors. Here, we aimed to assess the association between incident cancer and risk of death from pneumonia in Japanese in a large population‐based cohort study. Methods We used the data from The Japan Public Health Center‐based Prospective Study (JPHC Study), which enrolled subjects aged 40 to 69 between 1990 and 1994 and followed their cancer incidence and mortality until 2013. After identifying 103,757 eligible subjects for analysis and imputing missing data on covariates by the chained equations approach, we conducted propensity score‐matched analysis for 1:4 matching, leaving 14,520 cases diagnosed with cancer and 48,947 controls without cancer during the study period for final analysis. A Cox proportional hazards regression model was used to estimate the hazard ratio (HR) and corresponding confidence interval (CI) for the risk of death from pneumonia with comparison of cancer cases and cancer‐free controls. Results Compared to cancer‐free individuals, risk of death from pneumonia was significantly higher among those who had any diagnosed cancer (HR, 1.41; 95%CI, 1.08–1.84); those within 1 year of diagnosis (HR, 23.0; 95% CI, 2.98–177.3); within 1 to

Abstract Exposure to certain chemicals in the environment may contribute to the risk of developing cancer. Although cancer risk from environmental chemical exposure among general populations is considered low compared to that in occupational settings, many people may nevertheless be chronically exposed to relatively low levels of environmental chemicals which vary by such various factors as residential area, lifestyle, and dietary habits. It is therefore necessary to assess population-specific exposure levels and examine their association with cancer risk. Here, we reviewed epidemiological evidence on cancer risk and exposure to dichlorodiphenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFASs), cadmium, arsenic, and acrylamide. Japanese are widely exposed to these chemicals, mainly through the diet, and an association with increased cancer risk is suspected. Epidemiological evidence from Japanese studies to date does not support a positive association between blood concentrations of DDT, HCH, PCBs, and PFASs and risk of breast or prostate cancer. We established assessment methods for dietary intake of cadmium, arsenic, and acrylamide using a food frequency questionnaire. Overall, dietary intakes of cadmium, arsenic, and acrylamide were not significantly associated with increased risk of total cancer and major cancer sites in the Japan Public Health Center-based Prospective Study. However, statistically significant positive associations were observed between dietary cadmium intake and risk of estrogen receptor-positive breast cancer among postmenopausal women, and dietary arsenic intake and risk of lung cancer among male smokers. In addition, studies using biomarkers as exposure assessment revealed statistically significant positive associations between urinary cadmium concentration and risk of breast cancer, and between ratio of hemoglobin adducts of acrylamide and glycidamide and risk of breast cancer. Epidemiological studies of general populations in Japan are limited and further evidence is required. In particular, studies of the association of organochlorine and organofluorine compounds with risk of cancer sites other than breast and prostate cancer are warranted, as are large prospective studies of the association between biomarkers of exposure and risk of cancer.

Abstract The objective of this study was to identify the prevalence of family history of cancer using cohorts participating in the Japanese National Center Cohort Collaborative for Advancing Population Health (NC-CCAPH). We pooled data from seven eligible cohorts of the Collaborative with available data on family history of cancer. Prevalence of family history of cancer and corresponding 95% confidence intervals are presented for all cancers and selected site-specific cancers for the total population and stratified by sex, age, and birth cohort. Prevalence of family history of cancer increased with age ranging from 10.51% in the 15 to 39 year age category to 47.11% in 70-year-olds. Overall prevalence increased in birth cohorts from ≤ 1929 until 1960 and decreased for the next two decades. Gastric cancer (11.97%) was the most common site recorded for family members, followed by colorectal and lung (5.75%), prostate (4.37%), breast (3.43%) and liver (3.05%) cancer. Women consistently had a higher prevalence of family history of cancer (34.32%) versus men (28.75%). Almost one in three participants had a family history of cancer in this Japanese consortium study highlighting the importance of early and targeted cancer screening services.

Abstract The association between vitamin D and total and colorectal cancer risk was inconsistent in observational studies. We conducted Mendelian randomization approach in which the effect of confounding might be reduced. 110 single nucleotide polymorphisms (SNPs) associated with 25-hydroxyvitamin D concentrations were systematically selected according to the “GWAS Catalog” from all ethnic populations. For the SNP-vitamin D concentration association, 3978 individuals from two Japanese cohorts were included. Regarding SNP-total and colorectal cancer association, 4543 cancer cases and 14,224 controls and 7936 colorectal cancer cases and 38,042 controls, respectively were included from the Japanese Consortium of Genetic Epidemiology and other studies in Japan. There was no significant association between the genetically predicted plasma 25-hydroxyvitamin D concentration and total or colorectal cancer in any of the MR analyses. Odds ratios per doubling in vitamin D concentration were 0.83 (95% confidence interval [CI] 0.63–1.09) for total cancer and 1.00 (95% CI 0.80–1.24) for colorectal cancer in inverse variance weighted method, 0.83 (95% CI 0.57–1.19) for total cancer and 1.01 (95% CI 0.75–1.37) for colorectal cancer in MR-Egger method. Consistent with previous MR analyses among European ancestries, there was no significant association identified between 25-hydroxyvitamin D levels and total or colorectal cancer among Asians.

Background: Few cohort studies have used multiple surveys of screening attendance to simultaneously evaluate the effectiveness of fecal occult blood test (FOBT) and colonoscopy. Methods: We analyzed data of 30,381 middle-aged Japanese adults from a population-based prospective cohort study. Information on FOBT and colonoscopy was obtained from three questionnaire surveys (every 5 years). We classified the subjects into three groups: the FOBT (15,649 subjects), screening colonoscopy (2,407 subjects), and unscreened (12,325 subjects) groups. We used the unscreened group as the reference group to compare the mortality and incidence of colorectal cancer (CRC). Results: During the 14-year follow-up, 64, 12, and 104 CRC deaths were identified in the FOBT, screening colonoscopy, and unscreened groups, respectively. The risk of CRC death reduced with increasing the number of FOBTs (P for trend = 0.02) and was reduced by 44% in the subjects screened twice or thrice using FOBT (hazard ratio [HR] 0.56; 95% confidence interval [CI], 0.33–0.94). Significant decreases were seen for the incidence of CRC but not seen for the incidence of non-advanced CRC in the FOBT group. Concerning the screening colonoscopy, subjects screened at the start of follow-up showed a 69% reduced risk of CRC death (HR 0.31; 95% CI, 0.10–0.9996). Significant decreases were also seen for the incidence of CRC and non-advanced CRC in the subjects screened at the start of follow-up. Conclusion: FOBT, depending on the number of FOBTs, and colonoscopy, depending on recency, reduced the risk of death due to CRC and the incidence of CRC.

Abstract The number of long-term survivors after a cancer diagnosis is increasing. Few investigations have compared survivors’ diets to their original pre-diagnosis dietary pattern or with the patterns of cancer-free controls. We examined the dietary changes in survivors for five years (i.e. before to after diagnosis) in cancer survivors, comparing them with cancer-free controls in a prospective cohort study in Japan. Using 1995–1998 for the baseline and 2000–2003 for the follow-up survey, a validated food frequency questionnaire was administered to 33,643 men and 39,549 women aged 45–74 years. During the follow-up period, 886 men and 646 women had developed cancer. Participants that had not been diagnosed with cancer served as controls. There was a greater decrease in the calorie intake (median change: − 168 kcal/d [Interquartile range: − 640, 278]) in male cancer survivors compared to controls (− 33 kcal/d [− 453, 380], P

Background: Helicobacter pylori (H. pylori) is an established causative factor of gastric cancer. Although the expansion of insurance coverage has led to an increase in the number of patients treated for H. pylori, the population impact of eradication treatment for H. pylori has been scarcely investigated. This study aimed to clarify the long-term responses of H. pylori antibody titer after eradication treatment using large scale cross-sectional data from the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study). Methods: A total of 55,282 Japanese participants aged 40 to 74 years residing in 16 areas provided blood samples from 2011 through 2016. From these, treated (n = 6,276) and untreated subjects who were seropositive for H. pylori or had serological atrophy (n = 22,420) formed the study population (n = 28,696). Seropositivity was defined as an anti-H. pylori IgG titer of ≥10 U/mL. Antibody level was compared among subjects according to self-reported treatment history as untreated, and treated for less than 1 year (

Because of within-individual variation, surveys to estimate an individual’s usual food intake must be conducted over many days, in general. Here, using non-invasive biomarkers, we examined the number of measurements required to screen for the usual intake of fruit and vegetables, in addition to sodium, potassium, and the sodium-to-potassium (Na/K) ratio. Participants were 202 subjects aged 40–74 years from five areas of Japan who completed weighed food records (WFR) and five 24-hour urinary collections (24-h UCs) between 2012 and 2013. The number of 24-h UCs required to screen for intake that deviated from guidelines estimated by the WFR and their accuracies were assessed by the area under the curve (AUC) in a receiver-operating characteristics (ROC) analysis. The single urinary excretion of sodium, potassium, and the Na/K ratio showed moderate performance (AUC value: >0.7) in discriminating deviations from their criteria by respective intake based on the WFR. Urinary potassium excretion also showed moderate performance (AUC value: >0.7) in estimating the intake of vegetables but could not be used to estimate fruit intake even after five collections. The non-invasive measurement of biomarkers in a single 24-h UC showed moderate performance in screening the usual intake of vegetables, as measured based on the 12-day WFR, as well as of sodium, potassium, and the Na/K ratio.

Abstract The study aimed to evaluate the association between green tea and coffee consumption and the risk of kidney cancer using data from a large prospective cohort study in Japan (the Japan Public Health Center-based Prospective Study: JPHC Study). A total of 102,463 participants aged 40–69 were followed during 1,916,421 person-years (mean follow-up period, 19 years). A total of 286 cases of kidney cancer (199 in men, 87 in women) were identified. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) while adjusting for potential confounders. No statistically significant association between green tea intake and kidney cancer risk was found in the total population. Among women who consumed more than five cups of green tea per day, a statistically significant decreased risk was shown with a HR of 0.45 (95% CI: 0.23–0.89), compared to women who rarely consumed green tea. For coffee consumption, the association of kidney cancer risk was not statistically significant. This large prospective cohort study indicated green tea intake may be inversely associated with kidney cancer risk in Japanese adults, particularly in Japanese women.

Abstract Although a positive link between hypertension and intraocular pressure (IOP) has been suggested, the individual effects of systolic and diastolic blood pressure (SBP and DBP, respectively) on IOP remain unclear, particularly among Japanese populations. Here, we conducted a large-scale, cross-sectional study to determine individual and combined effects of SBP/DBP and hypertension on IOP. In total, 6783 Japanese people aged over 40 years underwent systemic and ophthalmological examinations, including measurements of blood pressure and IOP, conducted using non-contact tonometers. After adjusting for a priori known confounding factors, SBP and DBP levels were found to be positively correlated with IOP levels. The multivariable-adjusted odds ratio when comparing the hypertensive and normotensive groups for the prevalence of ocular hypertension was 1.88 (95% confidence interval, 1.14–3.08). When analysing the combined effects of SBP and DBP on ocular hypertension, SBP elevation had a greater effect on ocular hypertension than DBP increase. In conclusion, SBP and DBP levels and the prevalence of systemic hypertension were found to be positively associated with IOP levels and the prevalence of ocular hypertension in an ophthalmologically healthy Japanese population. Our findings suggest that systemic blood pressure control may be key for controlling IOP.

Abstract Circadian misalignments have been linked to adverse cardiometabolic outcomes. However, the association between irregular daily routine and the risk of cardiovascular disease (CVD) remains unknown. We examined this association in a prospective study in Japan. The study included 78,115 Japanese participants aged 45–74 years. The self-reported daily routine was evaluated using the question, ‘Is your daily routine or activity schedule regular?’ The response (yes/no) was obtained as a binary variable. Cox proportional hazard regression analysis was used to estimate the hazard ratios and 95% confidence intervals for the association between an irregular daily routine and CVD incidence risk. Among the participants, 23.7% reported an irregular daily routine. During the mean follow-up period of 13.3 years, we observed 4641 CVD events. An irregular daily routine was significantly associated with increased risks of CVD and total stroke in women, but not in men. This positive association between an irregular daily routine and the risk of CVD was weak in the high vegetable and fruit consuming population. An irregular daily routine is positively associated with the risk of incident CVD, especially in women. These associations may be weak in populations that consume a diet rich in vegetables and fruits.

Abstract We evaluated the association between vegetable and fruit consumption – particularly flavonoid-rich fruits – in mid-life and major depressive disorder (MDD) in later life. We also evaluated the association of nutrients in fruits and vegetables with MDD. Vegetable and fruit consumption and nutrient intake for 1204 individuals were averaged from data obtained in 1995 and 2000. MDD was diagnosed by certified psychiatrists in 2014–2015. Logistic regression was used to examine the odds of MDD according to quintile of vegetable and fruit consumption and quartile of nutrient intake. We fitted two regression models, using hierarchical adjustment for age, sex, employment status, alcohol consumption, current smoking, and physical activity. Bias-corrected and accelerated bootstrap confidence intervals were used to obtain accurate information. In fully adjusted models, the highest quintile of total fruit consumption excluding juice and flavonoid-rich fruit consumption showed decreased odds of MDD compared with the lowest quintile (OR = 0.34, 95% CI = 0.15–0.77; OR = 0.44, 95% CI = 0.20–0.97, respectively). No significant association was found for total vegetables and fruits, total vegetables, or total fruits. No significant association was found for any nutrient. This study provides novel information on the association between MDD and flavonoid-rich fruits.

Abstract This study investigates the longitudinal association between living arrangements and psychiatrists’ diagnosis of depression in the general population. In 1990, 1254 Japanese men and women aged 40–59 years were enroled and completed questionnaires on the living arrangement in the Japan Public Health Center-based Prospective Study (JPHC Study) and participated in a mental health screening (2014–2015). The study diagnosed a major depressive disorder (MDD) assessed by well-trained certified psychiatrists through medical examinations. During the follow-up, a total of 105 participants (36 men and 69 women) aged 64–84 years were diagnosed with MDD by psychiatrists. Living with a child (ren) was associated with a reduced risk of MDD for men but not for women; the respective multivariable ORs (95% CIs) were 0.42 (0.19–0.96) and 0.59 (0.32–1.09). These associations remained unchanged after adjusting for living with spouse and parent(s). In conclusion, living with a child (ren) was associated with a reduced risk of MDD in men, suggesting the role of a child (ren) in the prevention of MDD.

Background: Although prevalence of low birth weight has increased in the last 3 decades in Japan, no studies in Japanese women have investigated whether birth weight is associated with the risk of pregnancy complications, such as pregnancy-induced hypertension (PIH) and gestational diabetes mellitus (GDM). Methods: We used data from the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT), a population-based cohort study in Japan that launched in 2011. In the main analysis, we included 46,365 women who had been pregnant at least once, for whom information on birth weight and events during their pregnancy was obtained using a self-administered questionnaire. Women were divided into five categories according to their birth weight, and the relationship between birth weight and risk of PIH and GDM was examined using multilevel logistic regression analyses with place of residence as a random effect. Results: Compared to women born with birth weight of 3,000–3,999 grams, the risk of PIH was significantly higher among women born

IntroductionAutoantibodies against inflammatory cytokines may be used for the prevention of atherosclerosis. Preclinical studies consider colony-stimulating factor 2 (CSF2) as an essential cytokine with a causal relationship to atherosclerosis and cancer. We examined the serum anti-CSF2 antibody levels in patients with atherosclerosis or solid cancer.MethodsWe measured the serum anti-CSF2 antibody levels via amplified luminescent proximity homogeneous assay-linked immunosorbent assay based on the recognition of recombinant glutathione S-transferase-fused CSF2 protein or a CSF2-derived peptide as the antigen.ResultsThe serum anti-CSF2 antibody (s-CSF2-Ab) levels were significantly higher in patients with acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD) compared with healthy donors (HDs). In addition, the s-CSF2-Ab levels were associated with intima-media thickness and hypertension. The analyzes of samples obtained from a Japan Public Health Center-based prospective study suggested the utility of s-CSF2-Ab as a risk factor for AIS. Furthermore, the s-CSF2-Ab levels were higher in patients with esophageal, colorectal, gastric, and lung cancer than in HDs but not in those with mammary cancer. In addition, the s-CSF2-Ab levels were associated with unfavorable postoperative prognosis in colorectal cancer (CRC). In CRC, the s-CSF2-Ab levels were more closely associated with poor prognosis in patients with p53-Ab-negative CRC despite the lack of significant association of the anti-p53 antibody (p53-Ab) levels with the overall survival.ConclusionS-CSF2-Ab was useful for the diagnosis of atherosclerosis-related AIS, AMI, DM, and CKD and could discriminate poor prognosis, especially in p53-Ab-negative CRC.

Abstract Background Many epidemiological studies have reported the association between exposure to particulate matter and mortality, but long-term prospective studies from Asian populations are sparse. Furthermore, associations at low levels of air pollution are not well clarified. Here, we evaluated associations between long-term exposure to particulate matter

The association between sleep and stress and cancer is underinvestigated. We evaluated these factors in association with gastric cancer (GC). Five case-control studies from the Stomach Cancer Pooling (StoP) Project were included. We calculated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for sleep duration and stress level in association with GC through multiple logistic regression models adjusted for several lifestyle factors. The analysis included 1293 cases and 4439 controls, 215 cardia and 919 noncardia GC, and 353 diffuse and 619 intestinal types. Sleep duration of ≥9 h was associated with GC (OR =1.57, 95% CI = 1.23–2.00) compared to 8 h. This was confirmed when stratifying by subsite (noncardia OR = 1.59, 95% CI = 1.22–2.08, and cardia OR = 1.63, 95% CI = 0.97–2.72) and histological type (diffuse OR = 1.65, 95% CI = 1.14–2.40 and intestinal OR = 1.24, 95% CI = 0.91–1.67). Stress was associated with GC (OR = 1.33, 95% CI = 1.18–1.50, continuous). This relationship was selectively related to noncardia GC (OR = 1.28, 95% 1.12–1.46, continuous). The risk of diffuse (OR = 1.32, 95% CI = 1.11–1.58) and intestinal type (OR = 1.23, 95% CI = 1.07–1.42) were higher when stress was reported. Results for the association between increasing level of stress and GC were heterogeneous by smoking and socioeconomic status (p for heterogeneity = 0.02 and

Abstract Globally, sugary drinks are widely consumed, however, few epidemiologic studies have investigated the association between sugary drink consumption and risk of kidney and bladder cancer. We examined the association of sugary drinks with risk of kidney and bladder cancer in 73,024 participants from the Japan Public Health Center-based Prospective Study who reported no history of cancer. Sugary drink consumption was assessed using a validated food frequency questionnaire at study baseline (1995–1999). Individuals were followed to December 31, 2013. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs). During 1,069,815 person years of follow-up, 169 kidney cancer and 297 bladder cancer cases were documented. After adjusting for potential confounders, no greater risk of kidney and bladder cancer was observed. However, sugary drink consumption was positively associated with the risk of kidney cancer (HR for 100 ml/day increase in consumption was 1.11 [95% CI 1.01–1.22]) and bladder cancer (HR for 100 ml/d increase in consumption was 1.11 [95% CI 1.01–1.22]) among women after exclusion of cases diagnosed in the first three years of follow-up. In this large prospective cohort, consumption of sugary drinks was significantly associated with a small increase in hazard ratio for kidney and bladder cancer among women after exclusion of cases diagnosed within the first three years.

Abstract Background Income inequality has dramatically increased worldwide, and there is a need to re-evaluate the association between socio-economic status (SES) and depression. Relative contributions of household income and education to depression, as well as their interactions, have not been fully evaluated. This study aimed to examine the association between SES and depressive symptoms in Japanese adults, focusing on interactions between education and household income levels. Methods This cross-sectional study used data from baseline surveys of two cohort studies. Participants were 38,499 community-dwelling people aged 40–74 years who participated in baseline surveys of the Murakami cohort study (2011–2012) and Uonuma cohort study (2012–2015) conducted in Niigata Prefecture, Japan. Information regarding marital status, education level, household income, occupation, activities of daily living (ADL), and history of cancer, myocardial infarction, stroke, and diabetes was obtained using a self-administered questionnaire. Depressive symptoms were examined using the Center for Epidemiologic Studies Depression Scale (CES-D). Logistic regression analysis was used to obtain odds ratios (ORs). Covariates included age, sex, marital status, education, household income, occupation, ADL, and disease history. Results Individuals with higher education levels had lower ORs (adjusted P for trend = 0.0007) for depressive symptoms, independently of household income level. The OR of the university-or-higher group was significantly lower than that of the junior high school group (adjusted OR = 0.79). Individuals with lower household income levels had higher ORs (adjusted P for trend

Abstract Background B vitamins and methionine are essential substrates in the one-carbon metabolism pathway involved in DNA synthesis and methylation. They may have essential roles in cancer development. We aimed to evaluate the associations of dietary intakes of vitamin B12, vitamin B6, folate, and methionine with the risk of esophageal cancer (EC) using data from the Japan Public Health Center-based Prospective Study. Methods We included 87,053 Japanese individuals who completed a food frequency questionnaire and were followed up from 1995–1998 to 2013 and 2015. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by Cox proportional-hazard regression across quintiles of dietary intakes of B vitamins and methionine. Results After 1,456,678 person-years of follow-up, 427 EC cases were documented. The multivariable HR (95% CI) of incident EC in the highest versus lowest quintile of dietary intake of vitamin B12 was 1.75 (1.13–2.71; p-trend=0.01). Stratification analysis based on alcohol consumption showed that higher dietary intakes of vitamin B12 and methionine were associated with an increased risk of EC among never-drinkers; HRs (95% CIs) were 2.82 (1.18–6.74; p-trend=0.009; p-interaction=0.18) and 3.45 (1.32–9.06; p-trend=0.003; p-interaction 0.02) for vitamin B12 and methionine, respectively. Meanwhile, there was no association between vitamin B12 and methionine intake with the risk of EC among drinkers. There were no associations between dietary intake of folate or vitamin B6 and the risk of EC. Conclusion Dietary intake of vitamin B12 was positively associated with the risk of EC in the Japanese population.

Abstract General population-based cohort studies provide solid evidence on mass Helicobacter pylori (HP) eradication effects. Self-reported questionnaires are occasionally used in such studies to ascertain the HP eradication history. However, reports on the reliability of these questionnaires are lacking. This general population-based cohort study included 899 individuals with HP infection at the baseline survey who were reported to have eradicated it at the 5-year follow-up survey. Of these, the medical records of 280 patients were available for investigation, and the HP eradication status of 93 individuals was ascertained. Their medical records were reviewed, and the reliability of the self-reported questionnaire responses was assessed. Of the 91 individuals who successfully eradicated HP based on the medical records, 90 (98.9%) answered the self-reported questionnaire correctly, with an unweighted kappa value of 0.661 (p

Abstract Background Ischemic stroke, including transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI), is a serious health problem in the aging society. Thus, this study aimed to identify TIA and aCI biomarkers. Methods In 19 patients with TIA, candidate antigens recognized by serum IgG autoantibodies were screened using a human aortic endothelial cell cDNA library. Through amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), serum antibody levels against the candidate antigens were examined in healthy donor (HD), TIA, and aCI cohorts (n = 285, 92, and 529). The plasma antibody levels in the Japan Public Health Center-based Prospective Cohort Study (1991–1993) were also examined. Results The candidate antigens were aldolase A (ALDOA) and fumarate hydratase (FH). In AlphaLISA, patients with TIA or aCI had higher anti-ALDOA antibody (ALDOA-Ab) and anti-FH antibody (FH-Ab) levels than the HDs (P

Abstract Heterocyclic aromatic amines (HAAs), which are formed from the reaction of creatine or creatinine, amino acids, and sugars in meat and fish cooked at high temperatures, have been shown to be mutagenic in bacterial assays and carcinogenic in animal models. Following advances in the dietary assessment of HAA intake in epidemiological studies - including development of a validated meat-cooking module and a specialized food composition database - a number of epidemiological studies have specifically examined the association of HAA intake and cancer risk, most of which were conducted in Western countries. Given that dietary habits and cooking methods differ across countries, however, epidemiological investigation of dietary HAA intake requires a population-specific assessment method. Here, we developed a practical method for assessing dietary HAA intake among Japanese using a food frequency questionnaire (FFQ) and evaluated its validity for use in epidemiological studies by comparison with 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) levels in human hair. The Japan Public Health Center-based Prospective Study reported that daily intake of HAAs among Japanese was relatively low, and that more than 50% of total intake in mainland Japan was derived from fish. Only four case-control studies in Japan have been reported so far, for colorectal, stomach and prostate cancer, and colorectal adenoma. A statistically significant positive association was found between 2-amino-3,4-dimethylimidazo [4,5-f] quinoline (MeIQ) and the risk of colorectal adenoma and between individual and total HAAs and the risk of prostate cancer. In contrast, no association was observed for colorectal or stomach cancer, or for colorectal adenoma among men. We also found that the limited and inconsistent findings among epidemiological studies are due to the difficulty in assessing exposure levels of HAAs. In addition to further evidence from prospective cohort studies in Japanese based on dietary HAA intake estimated by FFQs, studies using other methods to assess HAA exposure, such as biomarkers, are highly anticipated.

Introduction: The urinary sodium-to-potassium ratio is an indicator of dietary sodium intake and has been associated with reduced kidney function. However, less is known about its association with albuminuria, the other key component of chronic kidney disease, in the community-dwelling adult population. We examined the association of the spot urinary sodium-to-potassium ratio with albuminuria and compared spot urinary and dietary sodium-to-potassium ratios. Methods: We quantified the association of the urinary sodium-to-potassium ratio with albuminuria in 6,274 Japanese adults (age, 40–97 years; 50.9% women) based on spot urine samples. We performed linear and logistic regression modeling to account for potential confounders. Elevated albuminuria was defined as a spot urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g. We secondarily evaluated the dietary sodium-to-potassium ratio based on a food-frequency questionnaire. Results: The median spot urinary and dietary sodium-to-potassium ratios were 2.70 (interquartile interval, 1.87–3.83) and 1.50 (1.21–1.84), respectively. The median ACR was 11.0 (6.0–24.0) mg/g. In a multivariable linear regression model, the spot urinary sodium-to-potassium ratio (per increment) was significantly associated with the natural logarithm of the ACR (regression coefficient, 0.023 [95% confidence interval [95% CI], 0.007–0.038]). This result was consistent in a multivariable logistic regression model (adjusted odds ratio, 1.08 [95% CI, 1.04–1.12]). The corresponding estimates for the dietary sodium-to-potassium ratio were 0.139 (95% CI, 0.087–0.191) and 1.28 (95% CI, 1.14–1.45), respectively. Conclusions: Both spot urinary and dietary sodium-to-potassium ratios were associated with elevated albuminuria in community-dwelling Japanese adults. Our findings further support the potential usefulness of the spot urinary sodium-to-potassium ratio as an indicator of sodium intake and suggest a link between sodium intake and kidney damage.

Background: Yoghurt can modify gastrointestinal disease risk, possibly acting on gut microbiota. Our study aimed at exploring the under-investigated association between yoghurt and gastric cancer (GC). Methods: We pooled data from 16 studies from the Stomach Cancer Pooling (StoP) Project. Total yoghurt intake was derived from food frequency questionnaires. We calculated study-specific odds ratios (ORs) of GC and the corresponding 95% confidence intervals (CIs) for increasing categories of yoghurt consumption using univariate and multivariable unconditional logistic regression models. A two-stage analysis, with a meta-analysis of the pooled adjusted data, was conducted. Results: The analysis included 6278 GC cases and 14,181 controls, including 1179 cardia and 3463 non-cardia, 1191 diffuse and 1717 intestinal cases. The overall meta-analysis revealed no association between increasing portions of yoghurt intake (continuous) and GC (OR = 0.98, 95% CI = 0.94–1.02). When restricting to cohort studies, a borderline inverse relationship was found (OR = 0.93, 95% CI = 0.88–0.99). The adjusted and unadjusted OR were 0.92 (95% CI = 0.85–0.99) and 0.78 (95% CI = 0.73–0.84) for any vs. no yoghurt consumption and GC risk. The OR for 1 category of increase in yoghurt intake was 0.96 (95% CI = 0.91–1.02) for cardia, 1.03 (95% CI = 1.00–1.07) for non-cardia, 1.12 (95% CI = 1.07–1.19) for diffuse and 1.02 (95% CI = 0.97–1.06) for intestinal GC. No effect was seen within hospital-based and population-based studies, nor in men or women. Conclusions: We found no association between yoghurt and GC in the main adjusted models, despite sensitivity analyses suggesting a protective effect. Additional studies should further address this association.

Abstract Background Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. Methods Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. Results The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297–311 of DIDO1, 426–440 of FOXJ2, and 607–621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case–control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. Conclusions Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.

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.