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Purpose: Fish and shellfish consumption is suggested to be a cancer-protective factor. However, studies investigating this association for gastric cancer, especially considering Helicobacter pylori (H. pylori) and atrophic gastritis (AG), are limited. We investigated gastric cancer risk associated with fish, shellfish, and n-3 polyunsaturated fatty acids (n-3 PUFAs) consumption among Japanese adults. Methods: 90,504 subjects enrolled in the Japan Public Health Center-based Prospective Study (JPHC Study) were followed until December 2013. Dietary intake data were collected using a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for gastric cancer risk associated with fish and shellfish consumption and marine n-3 PUFAs (sum of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA)) using Cox proportional hazards models. Among those with avaliable data, we conducted a subgroup analysis taking H. pylori infection and AG status into consideration. Results: There were 2,701 gastric cancer cases during an average of 15 years of follow-up. We observed an increased gastric cancer risk for salted fish consumption for men [HR for fifth quintile versus first quintile 1.43 (95% CI 1.18–1.75)] and for women [HR 1.33 (95% CI 1.00–1.77)]. We observed a weak risk reduction trend for women as the intake of marine n-3 PUFAs increased (p-trend:0.07). When we included H. pylori infection and atrophic gastritis status in the analysis, the associations diminished. Conclusion: Our results suggest that salted fish increases gastric cancer risk for men and women, while marine n-3 PUFAs marginally decreases this risk among women in Japan. [ABSTRACT FROM AUTHOR]

Summary: This 5-year longitudinal study investigated the relationship between depressive symptoms and fracture risk in a large Japanese cohort. Depressive symptoms were a significant risk factor for hip fractures in women. Purpose: A relationship between depressive symptoms and fractures has not been clearly demonstrated. We aimed to investigate the relationship between depressive symptoms and 5-year fracture risk in the Japan Public Health Center-based Prospective Study for the Next Generation. Methods: From 2011 to 2016, 114,092 participants were enrolled, and a follow-up survey was conducted 5 years later. We analyzed 30,552 men and 38,063 women aged 40–74 years who had no past fractures at baseline. Presence of depressive symptoms was defined as a modified 11-item Center for Epidemiological Studies Depression Scale score of 8 or higher, a history of depression, or use of antidepressants. Subjects were asked to report vertebral, upper limb, and/or hip fractures, except for traffic or work accidents, that occurred during the follow-up period. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for fracture were analyzed via logistic regression analysis to evaluate the relationship between depressive symptoms and fracture. Results: Women with depressive symptoms demonstrated a high AOR for hip fractures (AOR: 2.78, 95% CI: 1.30 – 5.92); this result was consistent in post menopause women. In men, this association was not found for any age group or any type of fracture. Conclusions: Depressive symptoms in women may increase the risk of hip fractures. Further studies are required to explore this relationship in more detail. [ABSTRACT FROM AUTHOR]

Background Recent studies have found that long-term changes in weight during adulthood are associated with a high risk of mortality. The objective of this study was to characterize body mass index (BMI) trajectories during adulthood and to examine the association between BMI trajectories and risk of death in the Japanese population. Methods The data were extracted from Japan Public Health Center-based Prospective Study—a population-based prospective cohort study in Japan with participants aged 40–69 years followed over 20 years. The participants were categorized into multiple BMI trajectory groups using the latent class growth model. The Cox proportional-hazards model was conducted using all-cause mortality and cause-specific mortality as outcomes and the identified BMI trajectory groups as a predictor. In total, 65 520 participants were included in the analysis. Results Six BMI trajectory groups were identified: underweight stable (Group 1), low-to-high normal (Group 2), high-to-low normal (Group 3), normal to overweight (Group 4), overweight to normal (Group 5) and normal to obese (Group 6). Our Cox models showed a higher hazard (risk) of all-cause mortality among participants in the BMI-declining groups [Group 3, adjusted hazard ratio (aHR): 1.10, 95% CI: 1.05–1.16; Group 5, aHR: 1.16, 95% CI: 1.08–1.26], underweight stable group (Group 1, aHR: 1.27, 95% CI: 1.21–1.33) and normal to obese group (Group 6, aHR: 1.22, 95% CI: 1.13–1.33) than Group 2 (low-to-high normal BMI trajectory). Conclusions Stable underweight and weight loss were associated with a high risk of mortality, both of which were uniquely observed in a Japanese population. [ABSTRACT FROM AUTHOR]

Objectives Life enjoyment, linked to the ability to engage pleasurably with one's environment, may be related to the risk of developing dementia. This prospective cohort study examined the association between level of life enjoyment and disabling dementia incidence among Japanese community residents. Methods The participants were Japanese, aged 45–74 years old at 5-years follow-up, in the Japan Public Health Center–based Study (N = 38,660). Psychological conditions and other confounding variables were identified through self-administered questionnaires. Incident disabling dementia registered based on the Japan's Long-Term Care Insurance system from 2006 to 2016. Hazard ratios [95% confidence intervals] were assessed using Cox proportional hazards models. Results Over a median follow-up period of 9.4 years, a total of 4,642 cases of disabling dementia developed. Level of life enjoyment was inversely associated with the risk of disabling dementia: the multivariable hazard ratios were 0.75 [0.67–0.84] (p <.001) and 0.68 [0.59–0.78] (p <.001) with medium and high life enjoyment, respectively, compared to low life enjoyment. Furthermore, the association between greater life enjoyment and low risk for disabling dementia was strongest in the subgroup with low–medium mental stress. In the high mental stress group, this association was evident for poststroke disabling dementia, but not for disabling dementia without a history of stroke. Discussion A higher level of life enjoyment was associated with a lower risk of disabling dementia, particularly in the low–medium mental stress group. This finding suggests the importance of having life enjoyment by managing mental stress for reducing risk of disabling dementia. [ABSTRACT FROM AUTHOR]

We aimed to validate a method for assessing trans -fatty acid (TFA) intake in the Japanese population using the FFQ developed in the 1990s from a prospective study that was based on the Japan Public Health Center-based Prospective Cohort Study. For FFQ validation, we included 565 participants (Cohort I: n 215, Cohort II: n 350) aged 40–69 years. We used a 28-d dietary record (DR) over 1 year and two FFQ administered before and after DR assessment. We calculated total TFA intake, TFA from industrial oils (i-TFA) and TFA from ruminants (r-TFA) considering a database of measurements obtained mainly from Japan. Spearman's rank correlation coefficients (CC) were computed for validity and reproducibility. Energy adjustments were applied using two methods considering the TFA measurement: density method for TFA % of total energy and residual method for TFA g/d. The total TFA intake (% of the total energy intake) was 0·08–0·76 % (median, 0·27–0·37 %) in DR of both cohorts and was 0·00–1·13 % (median, 0·30–0·40 %) in FFQ. The i-TFA accounted for approximately 50 % of the total TFA intake in DR and approximately 40 % in FFQ. For total TFA (% of the total energy intake), CC were 0·54–0·69, and weighted κ coefficients were 0·88–0·92 for both cohorts. The de-attenuated CC was 0·46–0·62 for i-TFA (g/d) and 0·57–0·68 for r-TFA (g/d). Our study showed that the validity and reproducibility of TFA intake estimation using the FFQ were reasonable, suggesting its suitability among the Japanese population with low-TFA intake. [ABSTRACT FROM AUTHOR]

Background: Some studies have investigated the relation between dairy products and mortality, but with inconsistent results. Objective: We examined the association between the consumption of dairy products and the risk of all-cause, cancer-related, and cardiovascular disease (CVD)-related mortality. Methods: From the Japan Public Health Center-based Prospective (JPHC) study, 43,117 males and 50,193 females with no history of cancer or CVD finished the food frequency questionnaire (FFQ) and were included in the study. Intake of dairy products was assessed using the FFQ and adjusted for total energy by using the residual method. We used multivariate Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for mortality risk in males and females. Results: 14,211 deaths in males and 9547 deaths in females from all causes were identified during an average follow-up of 19.3 years. For males, total dairy consumption was nonlinearly and significantly associated with lower risk of mortality from all causes [the third quartile, HR = 0.87 (0.83, 0.91), the fourth quartile, HR = 0.89 (0.85, 0.94), P for nonlinearity < 0.001] and CVD [the third quartile, HR = 0.77 (0.70, 0.85), the fourth quartile, HR = 0.78 (0.70, 0.86), P for nonlinearity < 0.001]. Milk and fermented milk intake were inversely associated with all-cause and CVD-related mortality in males. Cheese consumption was inversely associated with CVD-related mortality among males. There was no association between total dairy intake and mortality risk among females. Conclusion: For Japanese people, consumption of dairy products was associated with a decreased risk of mortality from all-cause and cardiovascular diseases among males. [ABSTRACT FROM AUTHOR]

Background Although studies have found an association between chronic kidney disease (CKD) and cancer incidence, the results are inconsistent. Methods This study included participants in the Japan Public Health Center-based Prospective Study who had data on serum creatinine measurements. We assessed the association between estimated glomerular filtration rate (eGFR) and the risk of total and site-specific cancer incidence using a systematic survey in Japan. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for participant demographics and lifestyle factors. Results A total of 21 978 participants who met the inclusion criteria were followed up for a mean period of 12.9 years, during which a total of 2997 incident cancer cases were reported. In the multivariable adjusted models, an eGFR of <45 mL/min/1.73 m2 was not significantly associated with total cancer incidence (adjusted HR 1.22, 95% CI 0.94–1.60), compared with an eGFR of 60–89 mL/min/1.73 m2 (reference). The HR among those with eGFRs of ≥90 mL/min/1.73 m2 was 1.10 (95% CI 1.00–1.22). Conclusions In this large prospective study, a low eGFR was not significantly associated with an increased risk of total cancer incidence in patients with CKD, which may be partly due to an underpowered sample size. This finding may be due to the many shared risk factors between CKD and cancer. [ABSTRACT FROM AUTHOR]

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 <.001). On comparison with cancer-free controls, multiple linear regression analysis revealed a significantly larger reduction in energy-adjusted ethanol intake for male cancer survivors (β = − 0.36). There was no difference in changes in fruit and vegetable or red meat intake and no other significant differences in dietary changes between survivors and controls for either gender. This suggests that most dietary changes in survivors after cancer diagnosis are not systematically different from those that occur in people without a cancer diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the association between total soy, soy product (natto, miso and tofu) and isoflavone intake and incident disabling dementia in a Japanese population. Methods: We conducted a population-based prospective study in 18,991 men and 22,456 women. Intake of soy products and isoflavone was calculated using a validated food frequency questionnaire when participants were 45–74 years old (1995 and 1998). Incident disabling dementia was defined by the daily living disability status related to dementia in the long-term care insurance program of Japan from 2006 to 2016. Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) of disabling dementia were calculated by quintiles of total soy, individual soy product and isoflavone intake, using Cox proportional hazard regression models. Results: Total soy product intake was not associated with disabling dementia risk in both men and women. By individual soy products, natto intake was marginally inversely associated with disabling dementia in women (trend P = 0.050). When we stratified by age, this inverse association was clearer in women aged under 60 years (multivariate HR for the highest versus lowest quintile was 0.78, 95% CI 0.59–1.04, trend P = 0.020 for those aged under 60 years and 0.90, 95% CI 0.77–1.05, trend P = 0.23 for those aged 60 years and older, respectively). Any soy product or isoflavone intake was not associated with disabling dementia risk in men. Conclusions: Although total soy product intake was not associated with disabling dementia risk, natto intake may contribute to reducing the risk of disabling dementia in women, especially in those aged under 60 years. [ABSTRACT FROM AUTHOR]

Background: A dose-response and nonlinear association between fruit and vegetable intake and mortality has been reported in Europe and the United States, but little is known about this association in Asia.Objectives: This study aimed to evaluate the association of fruit and vegetable intake with all-cause, cancer, cardiovascular, and respiratory disease mortality in a Japanese cohort.Methods: In the Japan Public Health Center-based prospective study, we included 94,658 participants (mean age: 56.4; 46.0% male) without cancer and cardiovascular disease at baseline. Information on fruit and vegetable intake was collected using a validated FFQ. The Cox proportional hazard model was used to estimate HRs and 95% CIs of each quintile of fruit and vegetable intake, separately, in relation to all-cause and cause-specific mortality using the first quintile as a reference. Nonlinear associations were evaluated using a likelihood ratio test, comparing a linear model with a restricted cubic spline model.Results: During a median of 20.9 follow-up years (IQR: 19.6-23.8 y), 23,687 all-cause deaths were documented. After adjusting for age, sex, and potential confounding factors, fruit and vegetable intake was nonlinearly and significantly associated with lower all-cause mortality, with the fourth and fifth quintiles having comparable HRs (fruit: fourth quintile HR: 0.91; 95% CI: 0.87, 0.95 and fifth quintile HR: 0.92; 95% CI: 0.88, 0.96; P-nonlinearity < 0.001; vegetable: fourth quintile HR: 0.92; 95% CI: 0.88, 0.97 and fifth quintile HR: 0.93; 95% CI: 0.89, 0.98; P-nonlinearity = 0.002). Fruit intake was significantly associated with lower cardiovascular mortality (HR in the fifth quintile: 0.91; 95% CI: 0.83, 0.99; P-nonlinearity = 0.01).Conclusions: In the Japanese population, higher intake of fruits and vegetables was nonlinearly associated with decreased all-cause mortality. These findings may contribute to the establishment of dietary recommendations for enhancing life expectancy in Asia. [ABSTRACT FROM AUTHOR]

Background: Several epidemiological studies have been conducted to draw consistent conclusions regarding the effect of dietary fibre on lung diseases and lung cancer. However, the effect of dietary fibre on the incidence of lung cancer remains unclear in an Asian population.Methods: We investigated the association between the intake of total dietary fibre and dietary fibre from different food sources and lung cancer incidence in a Japan public health centre-based prospective study (JPHC). A total of 73 405 participants (33 012 men and 40 393 women) aged 45-74 years were eligible for our study. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).Results: During a median follow-up of 18.0 years, 1546 (1042 men and 504 women) newly diagnosed cases of lung cancer were ascertained. In the multivariable models, total dietary fibre intake was inversely associated with lung cancer risk in men, the HRs Q5 vs Q1 (95% CI) were 0.77 (0.62 to 0.94), P-trend = 0.020. Dietary fibre intake from vegetables was protectively associated with lung cancer risk in men [HR Q5 vs Q1 (95% CI): 0.80 (0.64 to 0.99), P-trend = 0.053]. However, no such association was observed in women.Conclusions: In men, a high intake of total dietary fibre may have preventive benefits for lung cancer incidence: dietary fibre intake from vegetables was associated with a lower incidence of lung cancer. However, similar associations did not appear in women. Further investigations are required to confirm the association between dietary fibre and lung cancer risk in women. [ABSTRACT FROM AUTHOR]

Background: The association between body mass index (BMI) and oesophageal cancer (OC) has been consistently negative among Asians, whereas different associations based on histological OC subtypes have been observed in Europeans and North Americans. We examined the association between BMI and OC mortality in the Asia Cohort Consortium.Methods: We performed a pooled analysis to evaluate the association between BMI and OC mortality among 842 630 Asians from 18 cohort studies. Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs.Results: A wide J-shaped association between BMI and overall OC mortality was observed. The OC mortality risk was increased for underweight (BMI <18.5 kg/m2: HR = 2.20, 95% CI 1.80-2.70) and extreme obesity (BMI ≥35 kg/m2: HR = 4.38, 95% CI 2.25-8.52) relative to the reference BMI (23-25 kg/m2). This association pattern was confirmed by several alternative analyses based on OC incidence and meta-analysis. A similar wide J-shaped association was observed in oesophageal squamous cell carcinoma (OSCC). Smoking and alcohol synergistically increased the OC mortality risk in underweight participants (HR = 6.96, 95% CI 4.54-10.67) relative to that in reference BMI participants not exposed to smoking and alcohol.Conclusion: Extreme obesity and being underweight were associated with an OC mortality risk among Asians. OC mortality and BMI formed a wide J-shaped association mirrored by OSCC mortality. Although the effect of BMI on OSCC and oesophageal adenocarcinoma mortality can be different in Asians, further research based on a large case-control study is recommended. [ABSTRACT FROM AUTHOR]

Background: Increasing proportions of smokers in Japan smoke <10 cigarettes per day (CPD). Yet, the health risks of low-intensity smoking in Asia are poorly understood.Methods: We performed a pooled analysis of 410 294 adults from nine population-based prospective cohort studies participating in the Japan Cohort Consortium. Cigarette-use data were collected at each study baseline in 1983-1994. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality were calculated using multivariable-adjusted Cox regression by CPD among current smokers and by age at cessation among former smokers, with never smokers as the referent group. Pooled HRs and CIs were computed using a random-effect model.Results: The smoking prevalence was 54.5% in men and 7.4% in women. About 15.5% of male and 50.4% of female current smokers smoked 1-10 CPD (low-intensity). Both male and female low-intensity smokers had higher all-cause mortality risks than never smokers. Risks were further higher with increasing CPD in a dose-response manner. HRs (95% CIs) were 1.27 (0.97-1.66), 1.45 (1.33-1.59) and 1.49 (1.38-1.62) for 1-2, 3-5 and 6-10 CPD, respectively, in men; 1.28 (1.01-1.62), 1.49 (1.34-1.66) and 1.68 (1.55-1.81) for 1-2, 3-5 and 6-10 CPD, respectively, in women. Similar associations were observed for smoking-related causes of death. Among former low-intensity smokers, younger age at cessation was associated with lower mortality risk.Conclusions: Smoking very low amounts was associated with increased mortality risks in Japan. All smokers should quit, even if they smoke very few CPD. [ABSTRACT FROM AUTHOR]

Background: Meat, fish, and fatty acid intakes have been reported to be associated with non-Hodgkin lymphoma (NHL), although results have been inconclusive. We hypothesized that red meat and SFA intakes increase NHL risk, and fish and PUFA intakes decrease NHL risk.Objectives: We investigated the association between NHL incidence and meat, fish, and various fatty acid type intakes using the Japan Public Health Center-based Prospective Study.Methods: The current cohort study included 93,366 participants aged 45-74 y who were eligible for analysis; they were followed up until December 2012. Participants answered an FFQ between 1995 and 1999. We analyzed the effects of meat, fish, total fatty acid, SFA, and PUFA intakes on NHL incidence using the Cox proportional hazard model.Results: The median age was 57 y (IQR: 51-63 y), and 46.5% of the participants were men. Participants were followed up for 1,345,001 person-years, and 230 patients with NHL were identified. Total fatty acid and SFA intakes were associated with an increased incidence of NHL, with an adjusted HR of 1.56 (95% CI: 1.04, 2.34 highest compared with lowest quartile; P-trend = 0.062), and 1.63 (95% CI: 1.11, 2.41; P-trend = 0.074), respectively. In subtype analysis, total fatty acid and SFA intakes were also associated with increased incidence of follicular lymphoma but were not significantly associated with diffuse large B-cell lymphoma. Conversely, total meat, processed meat, unprocessed meat, red meat, poultry, fish, MUFA, PUFA, n-3 (ω-3) PUFA, and n-6 (ω-6) PUFA intakes were not significantly associated with the incidence of NHL or its subtypes.Conclusions: Total fatty acid and SFA intakes were associated with increased incidence of NHL in the Japanese adult population. Further large-scale studies are warranted to test whether fatty acid intakes affect the development of NHL. [ABSTRACT FROM AUTHOR]

Background: Vegetable and fruit consumption may have a protective effect against several types of cancer. However, evidence suggesting that increased intake of vegetables and fruits, their subtypes, or the antioxidant nutrients they contain in abundance decreases the risk of bladder cancer is limited.Methods: This study included 80,952 participants from the Japan Public Health Center-based Prospective Study, who responded to a food frequency questionnaire in a 5-year follow-up survey in 1995-1998 and were followed up until December 2015 to investigate the associations between intake of vegetables and fruits, their subtypes, or the antioxidant nutrients and bladder cancer risk using Cox proportional hazards regression models.Results: Within 1,287,514 person-years of follow-up, 401 bladder cancer cases (307 men and 94 women) were diagnosed. No association was found between intake of total vegetable and fruit, total vegetable, total fruit, subtypes of vegetables and fruits, or antioxidant nutrients and bladder cancer risk in both men and women, even in the analyses conducted among men stratified by smoking status.Conclusions: In this population, the consumption of vegetables and fruits was not associated with the risk of bladder cancer. [ABSTRACT FROM AUTHOR]

Background: Evidence of the association between chronic low-grade inflammation, as reflected by C-reactive protein (CRP) measurements, and cancer risk is equivocal. Specifically, few studies have examined this in uncommon cancers and Asian populations.Methods: We utilised a case-cohort design consisting of multi-types of cancer (N = 3608), and a random subcohort (N = 4432) in a Japanese large population-based study, with a median follow-up time of 15.6 years, and measured baseline plasma CRP using high sensitivity assay. The hazard ratios (HRs) were estimated using weighted Cox proportional hazards methods.Results: The multivariable-adjusted HR (95% confidence interval) for the top quartile of CRP was 1.28 (1.11‒1.48) (Ptrend < 0.001) for overall cancer compared to the bottom quartile of CRP. Among site-specific cancers, higher CRP levels were associated with an increased risk of colorectal, lung, breast, biliary tract, and kidney cancer, and leukaemia. These positive associations remained among participants after >3 years' follow-up. Furthermore, subgroup analyses for overall cancer robustly showed a positive association with CRP levels, regardless of sex and obesity.Conclusion: Our consistent findings suggested that chronic low-grade inflammation measured by CRP is associated with the risk of cancer. [ABSTRACT FROM AUTHOR]

Introduction: Studies investigating the risk of gallstones in the Japanese population are sparse. To our knowledge, this is the first prospective cohort study assessing risk factors of gallstones in Japan. Methods: A nationwide population-based prospective cohort of 112,109 men and women, aged 40–69 years, self-completed questionnaires at baseline regarding exposures to potential risk factors, between 1990 and 1994. The occurrence of gallstones and cholecystectomy for gallstones were ascertained from another questionnaire after 10 years. Odds ratios and the 95% confidence intervals were calculated using the multivariate logistic regression. Results: During the 10-year follow-up, 3,092 (5.0%) participants developed gallstones and 729 (1.2%) participants required cholecystectomy. Increasing age, high body mass index, and diabetes mellitus were associated with the risk of gallstones in both sexes. In men, weight gain or loss of >5 kg over the follow-up period and stress were associated with risk of gallstones, whereas alcohol intake was inversely associated with the risk. In women, weight gain of >5 kg during the follow-up period, smoking, menopause, and lipid-lowering drugs were associated with risk of gallstones, whereas late onset of menarche was inversely associated with risk of gallstones. The risk of cholecystectomy broadly reflected the risk of gallstones for both sexes respectively. Conclusion: Risk factors for both gallstones and cholecystectomy for gallstones are multifactorial and differ between men and women. Novel findings in this study include an inverse association between late onset of menarche and gallstones, and an association between self-reported stress in men and gallstones. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate the association between sugar or starch intake and the risk of type 2 diabetes (T2D) in middle-aged Japanese adults.Subjects/methods: Participants comprised 27,797 men and 36,880 women aged 45-75 years with no history of diabetes and critical illness before the second survey in the Japan Public Health Center-based Prospective Study. We calculated sugar (total sugar, total fructose, and sugar subtypes) and starch intakes (% energy/d) using a validated 147-item food frequency questionnaire, to estimate the average dietary intake over the previous year. T2D onset was defined by validated self-reports. ORs adjusted for potential confounders were estimated using multiple logistic regression with categorical and cubic spline models.Results: During the 5-year follow-up, 690 men and 500 women were identified with T2D. In women, the quartiles of total sugar or total fructose intakes were not significantly associated with T2D risk; however, the spline curves showed an increased risk at extremely high intake levels (ORs [95% CI]: 1.88 [1.07-3.31] at 30% energy/d for total sugar and 1.87 [1.10-3.16] at 14% energy/d for total fructose). Starch intake was positively associated with T2D risk among women in the categorical and spline models (ORs [95% CI]: 1.55 [1.13-2.12] at 50% energy/d). In men, sugar and starch intakes were not associated with T2D risk.Conclusions: In this large-scale population-based cohort study, starch intake was associated with an increased T2D risk in Japanese women. An increased risk with extremely high intake of total sugar or total fructose among women cannot be disregarded. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that consuming coffee may lower the risk of death, but evidence regarding tea consumption in Asians is limited. We examined the association between coffee and tea consumption and mortality in Asian populations.Methods: We used data from 12 prospective cohort studies including 248 050 men and 280 454 women from the Asia Cohort Consortium conducted in China, Japan, Korea and Singapore. We estimated the study-specific association of coffee, green tea and black tea consumption with mortality using Cox proportional-hazards regression models and the pooled study-specific hazard ratios (HRs) using a random-effects model.Results: In total, 94 744 deaths were identified during the follow-up, which ranged from an average of 6.5 to 22.7 years. Compared with coffee non-drinkers, men and women who drank at least five cups of coffee per day had a 24% [95% confidence interval (CI) 17%, 29%] and a 28% (95% CI 19%, 37%) lower risk of all-cause mortality, respectively. Similarly, we found inverse associations for coffee consumption with cardiovascular disease (CVD)-specific and cancer-specific mortality among both men and women. Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption.Conclusions: In Asian populations, coffee consumption is associated with a lower risk of death overall and with lower risks of death from CVD and cancer. Green tea consumption is associated with lower risks of death from all causes and CVD. [ABSTRACT FROM AUTHOR]

Background The association between total protein intake and all-cause mortality is inconsistent. Pneumonia is a major cause of death among the elderly, and the association between protein intake and pneumonia mortality warrants clarification. Objectives We aimed to examine the association between total, plant, and animal protein intake and pneumonia mortality in a prospective design. Methods The Japan Public Health Center (JPHC)–based Prospective Study prospectively follows 83,351 participants (37,652 men and 45,699 women). Total, plant, and animal protein intakes were calculated from a validated food-frequency questionnaire. A Cox hazards model was used to calculate HRs and 95% CIs, with adjustment for confounding factors. Results During ∼18.4 y of follow-up, 990 pneumonia deaths (634 men and 356 women) were observed. In the multivariable-adjusted model and in the model further adjusted for fatty acid intake, increase in total protein intake was marginally significantly associated with lower pneumonia mortality in women [lowest vs. highest quartile, HR (95% CI): 0.71 (0.53, 0.97), P -trend = 0.01 in the multivariable-adjusted model, and 0.70 (0.45, 1.06), P -trend = 0.05 in the fatty acid intake–adjusted model]. Total protein intake in men and animal and plant protein intake in both men and women were not significantly associated with pneumonia mortality in the fatty acid–adjusted model. Conclusions Although the HR in the highest quartile was not significant and further research to determine the upper limit of recommended protein intake is required, higher total protein intake was associated with lower pneumonia mortality in women. [ABSTRACT FROM AUTHOR]

Background The association of meat consumption with gastric cancer is inconclusive. Objectives We examined the association of meat consumption with gastric cancer risk among Japanese men and women. Methods This cohort study included 42,328 male and 48,176 female participants of the Japan Public Health Center–based Prospective Study, who were aged 45 to 74 y at recruitment. Dietary intake data were collected from 1 January 1995 to 31 December 1999 using a validated food-frequency questionnaire. HRs and 95% CIs for gastric cancer were estimated using Cox proportional hazards regression models. Results During a mean follow-up of 15 y, 1868 male and 833 female incident gastric cancer cases were identified. Intake of total and subtypes of meat was not associated with total gastric cancer. However, higher chicken consumption was associated with reduced distal gastric cancer risk in women (HR for quintile 5 vs. quintile 1: 0.75; 95% CI: 0.56, 0.99; P- trend = 0.027), with a similar but nonsignificant risk reduction among women with Helicobacter pylori (HR: 0.59; 95% CI: 0.29, 1.20; P- trend = 0.06) in subgroup analysis. Conclusions Meat consumption was not associated with total gastric cancer risk. [ABSTRACT FROM AUTHOR]

We sought to examine the prospective associations of specific fruit consumption, in particular flavonoid-rich fruit (FRF) consumption, with the risk of stroke and subtypes of stroke in a Japanese population. A study followed a total of 39 843 men and 47 334 women aged 44–76 years, and free of CVD, diabetes and cancer at baseline since 1995 and 1998 to the end of 2009 and 2012, respectively. Data on total and specific FRF consumption for each participant were obtained using a self-administrated FFQ. The hazard ratios (HR) of stroke in relation to total and specific FRF consumption were estimated through Cox proportional hazards regression models. During a median follow-up of 13·1 years, 4091 incident stroke cases (2557 cerebral infarctions and 1516 haemorrhagic strokes) were documented. After adjustment for age, BMI, study area, lifestyles, dietary factors and other risk factors, it was found that total FRF consumption was associated with a significantly lower risk of stroke in women (HR = 0·70; 95 % CI 0·58, 0·84), while the association in men was not significant (HR = 0·93; 95 % CI 0·79, 1·09). As for specific FRF, consumptions of citrus fruits, strawberries and grapes were found associated with a lower stroke risk in women. Higher consumptions of FRF, in particular citrus fruits, strawberries and grapes, were associated with a lower risk of developing stroke in Japanese women. [ABSTRACT FROM AUTHOR]

Purpose: Long-term associations of dietary glycemic index (GI) and glycemic load (GL) with mortality outcomes remain unclear. Methods: The present analysis included 72,783 participants of the Japan Public Health Center-based Prospective Study. Participants who responded to the 5-year follow-up questionnaire in 1995–1999 were followed-up until December 2015. We estimated the risk of total and cause-specific mortality associated with GI and GL using Cox proportional hazards regression models. Results: During 1,244,553 person years of follow-up, 7535 men and 4913 women died. GI was positively associated with all-cause mortality. As compared with the lowest quartile, the multivariable HR for those who had the highest quartile of GI was 1.14 (95% CI 1.08–1.20). The HRs for death comparing the highest with the lowest quartile were 1.28 (95% CI 1.14–1.42) for circulatory system diseases, 1.33 (95% CI 1.14–1.55) for heart disease, 1.32 (95% CI 1.11–1.57) for cerebrovascular disease, and 1.45 (95% CI 1.18–1.78) for respiratory diseases. GI was not associated with mortality risks of cancer and digestive diseases. GL showed a null association with all-cause mortality (highest vs lowest quartile; HR 1.04; 95% CI 0.96–1.12). However, among those who had the highest quartile of GL, the HRs for death from circulatory system diseases was 1.24 (95% CI 1.05–1.46), cerebrovascular disease was 1.34 (95% CI 1.03–1.74), and respiratory diseases was 1.35 (95% CI 1.00–1.82), as compared with the lowest quartile. Conclusion: In this large prospective cohort study, dietary GI and GL were associated with mortality risks. [ABSTRACT FROM AUTHOR]

Evidence of the association between dietary fiber intake and gastric cancer (GC) risk from prospective studies is limited. We examined the association between dietary fiber intake and GC risk in a large prospective study. A total of 91 946 eligible Japanese aged 45 to 74 years (42 773 men and 49 173 women) participated in a population‐based cohort study (Japan Public Health Center‐based prospective study). From a validated food frequency questionnaire with 138 food items, total and food source‐specific dietary fiber intake was calculated as exposure. The hazard ratio (HR) and the 95% confidence interval (CI) of GC incidence according to quintile of dietary fiber intake were examined after adjusting for confounding factors. In total, 2228 GC cases (1559 men and 669 women) were observed during the 15.0 years follow‐up. Total dietary fiber intake was not associated with GC risk; however, a marginally increased risk trend because of high HR in the highest quintile of total fiber intake was found in women (HR [95% CI] in Q5 vs Q1: 0.95 [0.79‐1.14], P for trend.30 in men, HR [95% CI] 1.25 [0.98‐1.61], P for trend.05 in women). Stratification by tumor location did not change the results. A marginal but not significant inverse trend was observed regarding cereal fiber intake and GC risk in men. Total dietary fiber intake was not associated with GC risk. Further studies are warranted to confirm this association. What's new? Since dietary fiber is abundantly contained in whole grains, fruits, and vegetables, it is expected to have beneficial effects on health. But so far, only the association with decreased colorectal cancer risk has been fully established. In a 15‐year prospective study with more than 2000 gastric cancer cases from 91 946 Japanese subjects, total dietary fiber intake was not associated with gastric cancer risk. However, a marginally increased association between total fiber intake and gastric cancer incidence in women, and a non‐significant inverse trend with cereal fiber intake in men, was observed. Stratification by tumor location did not change the results. [ABSTRACT FROM AUTHOR]

Background/objectives: The association of fermented soy products, separately from total soy products, with cardiovascular disease (CVD) and total cancer has not been reported. We examined this association in a population-based prospective cohort study in Japan.Subjects/methods: We studied 79,648 participants (42,788 women; 36,860 men) aged 45-74 years without a history of cancer, myocardial infarction, or stroke. Participants completed a food frequency questionnaire (1995-1998) and were followed to 2009-2012. Cox proportional hazards regression analysis was used to calculate the hazard ratios (HR) and 95% confidence intervals (CI) of incidence of CVD and total cancer according to quartiles of total soy products, nonfermented soy products, fermented soy products, miso soup, natto, total isoflavones from soy products, isoflavones from nonfermented soy products, and isoflavones from fermented soy products.Results: In women, we observed a significant inverse association between fermented soy product intake and the risk of CVD (multivariate HR in the highest compared with the lowest quartile of fermented soy product intake: 0.80; 95% CI: 0.68, 0.95; P for trend = 0.010), and also found significant inverse associations for natto and isoflavones among fermented soy products. In site-specific analysis, we observed a similar, significant inverse association between fermented soy product intake and the risk of stroke in women. We found no significant association between any soy product and risk of CVD in men or total cancer in both sexes.Conclusions: Intake of fermented soy products such as natto was inversely associated with the risk of CVD in women. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare the impact of fermented and unfermented soy intake, based on the following soy-derived products: tofu, soymilk, natto, and miso, on the risk of liver cancer among Japanese adults. Methods: 75,089 Participants of the Japan Public Health Center-based Prospective Study (JPHC Study) were followed from the time of the 5-year follow-up questionnaire until the end of 2012–2013. Subjects with available data on hepatitis B virus (HBV) and hepatitis C virus (HCV) infection status from blood samples (n = 14,016) and those who were anti-HCV antibody (anti-HCV) or hepatitis B virus antigen (HBsAg) positive (n = 1033) were also analyzed separately. Cox proportional hazard models were employed to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results: During 1,145,453 person-years, 534 newly diagnosed cases of liver cancer were identified in the JPHC Study. For miso intake among men, the multivariate-adjusted highest versus lowest quartile HR was 0.65 (95% CI, 0.48–0.89); p for trend = 0.006. Results were similar in those who were anti-HCV or HBsAg positive, 0.24 (0.08–0.70); p for trend = 0.004 highest versus lowest tertile. For the sub-analysis among only participants with known hepatitis infection status and HCV and HBsAg adjustment, a similar association was observed. In the multivariate complete cohort analysis, among women, the highest intake of fried tofu was inversely associated with the risk of liver cancer, HR = 0.45 (0.26–0.80); p for trend = 0.014. Conclusions: We observed no association between total soy intake, fermented and unfermented, and risk of liver cancer, and only an inverse association between miso intake and liver cancer among men. [ABSTRACT FROM AUTHOR]

Purpose: The present study aimed to examine the association between adherence to the Japanese diet and the subsequent risk of all-cause and cause-specific mortality using a large-scale cohort from settings all over Japan. Methods: We analyzed data from a cohort study of 92,969 Japanese adults aged 45–74 years, covering 11 public health center areas nationwide. We collected dietary information using a validated 147-item food frequency questionnaire. Adherence to the Japanese diet consisting of eight components (high intake of rice, miso soup, seaweeds, pickles, green and yellow vegetables, fish, and green tea; low intake of beef and pork) was assessed using 8-item Japanese Diet Index (JDI8) score, with scores ranging from 0 to 8. The Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for all-cause and cause-specific mortality. Results: During a median follow-up of 18.9 years, we documented 20,596 deaths. A higher JDI8 score was significantly associated with a lower risk for all-cause and cardiovascular disease (CVD) mortality. The multivariable-adjusted HR of all-cause and CVD mortality for the highest JDI8 score group (score of 6–8) versus the lowest JDI8 score group (score of 0–2) were 0.86 (95% CI 0.81–0.90, P trend < 0.001), and 0.89 (95% CI 0.80–0.99, P trend = 0.007), respectively. Conclusions: Adhering to the Japanese diet, as assessed by the JDI8, was associated with a decreased risk of all-cause and CVD mortality among adults living in multiple areas across Japan. [ABSTRACT FROM AUTHOR]

Background: Fruits and vegetables may induce greater satiety, reduce hunger, decrease energy intake, and modulate energy metabolism, thereby playing a role in weight loss. Objective: To determine the associations between changes in fruit and vegetable consumption and weight change over a 5-year interval in Japanese adults. Methods: This cohort study included 54,015 subjects (54.6% female, mean age 56.5 years) of the Japan Public Health Center-based Prospective Cohort Study who had no known history of major chronic diseases at baseline. Data on fruit and vegetable consumption were collected using a validated food frequency questionnaire. Body weight was self-reported. We used multivariable linear mixed-effects regression models to examine the associations between changes in fruit and vegetable consumption and change in body weight. Results: On average, body weight decreased by 25 g [95% confidence interval (CI), 3, 47] for every 100 g/d increase in total vegetable consumption. Change in fruit consumption was nonlinearly associated with weight change. Fruit consumption was directly associated with weight change among subjects who increased consumption (70 g; 95% CI, 39, 101) but was not associated with weight change among subjects who reduced or did not change fruit consumption. These associations did not vary by sex, age, and body mass index (BMI) at baseline. The association with vegetables was restricted to yellow/red vegetables (− 74 g; 95% CI, − 129, − 18) and allium vegetables (− 129 g; 95% CI, − 231, − 28). Lower-fiber vegetables were inversely associated with weight change, whereas lower-fiber fruits or higher-energy fruits were directly associated with weight change beyond 0 g/d change in consumption. Conclusions: Change in vegetable consumption was inversely associated with weight change while fruit consumption was positively associated with weight change among subjects who increased consumption. The influence of fruits and vegetables on weight change may depend on the characteristics of the fruits and vegetables. [ABSTRACT FROM AUTHOR]

Red meat or saturated fatty acid (SFA) intake has been reported to increase lung cancer (LC) risk in several western countries. However, in Asia, studies on the relationship between meat and SFA intake with LC incidence are still relatively insufficient, and their conclusions are inconsistent. We investigated the association of meat and SFA intake with LC incidence in a population‐based prospective cohort study in Japan. Cox regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for LC risk according to meat intake and SFA intake. A total of 73 187 participants (32 934 men and 40 253 women) aged 45 to 74 years participated in our study. During the follow‐up period of 1 151 839 person‐years (median, 16.0 year) from 1995 to 2013 for Cohort I and from 1998 to 2013 for Cohort II, 1315 (901 men and 414 women) newly diagnosed cases of LC were identified. In men, we found an adverse association between total red meat intake (HR and 95% CI: 1.25 [1.02‐1.53]; Ptrend =.008) and LC risk. Additionally, borderline statistically significant elevated risks of LC were seen with high intake of unprocessed red meat and processed red meat. However, no positive association between total red meat intake and LC risk was observed in women. In contrast, poultry and fish intake were not associated with LC risk in either men or women. We concluded that a high total intake of total red meat was associated with moderately elevated LC risk in men. What's new? Previous studies have indicated that high red meat intake increased lung cancer risk in the Caucasian population, but consistent findings have not been reported in the Asian population. Differences in the dietary patterns between Asian, European, and American populations may also influence the risk of lung cancer. In this large population‐based prospective cohort study carried out in Japan, the authors found that total red meat intake was positively associated with increased lung cancer incidence in men. In contrast, high poultry and fish intake were not associated with raised lung cancer incidence in either men or women in this Asian study. [ABSTRACT FROM AUTHOR]

Although the association between fruit consumption and CHD risk has been well studied, few studies have focused on flavonoid-rich fruits (FRF), in particular strawberries and grapes. We aimed to verify the association of total and specific FRF consumption with risk of CHD by a large prospective cohort study. A total of 87 177 men and women aged 44–75 years who were free of CVD and cancer at study baseline were eligible for the present analysis. FRF consumption was assessed using a FFQ. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) of CHD in relation to FRF consumption with adjustment for potential risk factors and confounders. During a mean follow-up of 13·2 years, we identified 1156 incident CHD cases. After full adjustment for covariates including demographics, lifestyles and dietary factors, the HR were 0·93 (95 % CI 0·77, 1·11), 0·91 (95 % CI 0·75, 1·11), 0·84 (95 % CI 0·67, 1·04) and 0·78 (95 % CI 0·62, 0·99) for the second, third, fourth and fifth quintiles compared with the lowest quintile of FRF consumption. Regarding specific fruits, we observed a significant inverse association for citrus fruit consumption and a borderline inverse association for strawberry consumption, while no association was observed for apple/pear or grape consumption. Although the associations appeared to be stronger in women, they were not significantly modified by sex. Higher consumption of FRF, in particular, citrus fruits, may be associated with a lower risk of developing CHD. [ABSTRACT FROM AUTHOR]

Background: Although many epidemiological studies have reported the preventive effects of soy products and isoflavones on prostate cancer, our previous studies reported that the association between soy and isoflavones and prostate cancer incidence differed according to stage. It is more important to identify modifiable risk factors related to lethal prostate cancer. Here, we investigated the association between soy, soy products and isoflavones intake and prostate cancer mortality, in a prospective study in Japan.Methods: We conducted a population-based prospective study in 43 580 Japanese men with no history of cancer or cardiovascular disease (aged 45-74 years). Participants completed a validated questionnaire which included 138 food items. We followed participants from 1995 to 2016. Hazard ratios (HRs) and 95% confidence intervals (CIs) of prostate cancer mortality were calculated according to quintiles of soy products and isoflavones intake, using Cox hazard proportional hazards regression.Results: During 16.9 years follow-up, we registered 221 deaths from prostate cancer. Isoflavones and soy products intake was associated with an increased risk of prostate cancer death, with multivariate HRQ5 vs. Q1=1.39, 95% CI = 0.87-2.20, p for trend = 0.04 for isoflavones and multivariate HRQ5 vs. Q1=1.76, 95% CI = 1.10-2.82, p for trend = 0.04 for soy food.Conclusions: Our study suggested that high intake of soy and isoflavones might increase the risk of prostate cancer mortality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Excess body weight is an established cause of postmenopausal breast cancer, but it is unknown if weight loss reduces risk.Methods: Associations between weight change and risk of breast cancer were examined among women aged 50 years and older in the Pooling Project of Prospective Studies of Diet and Cancer. In 10 cohorts, weight assessed on three surveys was used to examine weight change patterns over approximately 10 years (interval 1 median = 5.2 years; interval 2 median = 4.0 years). Sustained weight loss was defined as no less than 2 kg lost in interval 1 that was not regained in interval 2. Among 180 885 women, 6930 invasive breast cancers were identified during follow-up.Results: Compared with women with stable weight (±2 kg), women with sustained weight loss had a lower risk of breast cancer. This risk reduction was linear and specific to women not using postmenopausal hormones (>2-4.5 kg lost: hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70 to 0.96; >4.5-<9 kg lost: HR = 0.75, 95% CI = 0.63 to 0.90; ≥9 kg lost: HR = 0.68, 95% CI = 0.50 to 0.93). Women who lost at least 9 kg and gained back some (but not all) of it were also at a lower risk of breast cancer. Other patterns of weight loss and gain over the two intervals had a similar risk of breast cancer to women with stable weight.Conclusions: These results suggest that sustained weight loss, even modest amounts, is associated with lower breast cancer risk for women aged 50 years and older. Breast cancer prevention may be a strong weight-loss motivator for the two-thirds of American women who are overweight or obese. [ABSTRACT FROM AUTHOR]

This study evaluated the validity of self-reported periodontitis measures among 2404 Japanese adults aged 40 to 75 years. A self-administered questionnaire survey and a clinical periodontal examination were conducted from 2013 through 2016. The self-reported periodontitis questions included 3 sociodemographic, 3 health, and 5 periodontal health–related items. Based on the clinical case definition of periodontitis, 26.5% of participants were found to be periodontally healthy, 2.7% had mild periodontitis, 55.2% moderate periodontitis, and 15.6% severe periodontitis. No single self-reported question demonstrated satisfactory validity in predicting the presence or absence of periodontitis. The predictive ability in mild and/or moderate periodontitis was poor even after combining multiple sociodemographic, health, and periodontal health-related questions. In severe periodontitis, the model including age, sex, education level, smoking status, diabetes history, body mass index, informed by a dentist, gingival bleeding, calculus deposit, and tooth mobility, presented moderate predictive performance (C-statistic: 0.676, sensitivity: 65.2%, and specificity: 61.1%). An age-stratified analysis on severe periodontitis showed that sensitivity was higher, and specificity was lower in older age group (60-75 years) than younger age group (40-59 years). Further refinement of questions in the self-report is required to increase the accuracy of the prediction of clinical periodontitis. [ABSTRACT FROM AUTHOR]

Background: Soy is commonly consumed in east Asian countries and is suggested to reduce colorectal cancer (CRC) risk. However, results from epidemiologic studies are inconsistent, despite the anti-inflammatory and antiproliferative properties of soy isoflavones and soy protein.Objective: We evaluated the association between soy isoflavones and soy protein and CRC risk using 4 prospective cohort studies from China and Japan.Methods: Data were pooled from the Shanghai Women's Health Study (SWHS), Shanghai Men's Health Study (SMHS), Japan Public Health Center-based Prospective Study Cohort 1 (JPHC1), and Cohort 2 (JPHC2). Cox proportional hazards models estimated HRs and corresponding 95% CIs for the association of soy protein and isoflavone intake with CRC risk. The study included 205,060 individuals, among whom 2971 were diagnosed with incident CRC over an average follow-up of 12.7 y.Results: No statistically significant associations with CRC risk were observed for soy protein or isoflavone intake. No association was observed among ever smokers consuming higher isoflavones (HRisoflavones: 0.83; 95% CI: 0.68, 1.00) and soy protein (HRsoy protein: 0.81; 95% CI: 0.39, 1.10). However, risk reductions were observed among premenopausal women with a body mass index [BMI (kg/m2)] <23.0 at baseline for higher isoflavone (HRisoflavones: 0.58, 95% CI: 0.34, 0.98).Conclusions: No evidence for an overall reduction in CRC risk by increasing soy food intake (i.e., protein or isoflavones) was observed. However, the association between soy and CRC risk may vary by BMI, smoking, and menopausal status among women. Future investigations are needed to further understand the biologic mechanisms observed. [ABSTRACT FROM AUTHOR]

Purpose: It is unclear whether habitual intake of soy or isoflavones induces long-term changes in the concentrations of blood lipids and glycaemia. We examined the associations of soy food and isoflavone consumption with changes in blood lipids and HbA1c concentrations over 5 years among Japanese adults. Methods: This cohort study included 7252 subjects with no known history of major chronic disease at baseline. Soy intake was measured using a food frequency questionnaire; while the concentrations of serum lipids and HbA1c were measured using standard laboratory methods. We used multivariable linear mixed-effects models to examine the associations of changes in lipids and HbA1c concentrations with intakes of soy food and isoflavones. Results: Among the participants, mean age was 61 years, 67% were females and median intakes of soy and isoflavones were 95.3 g/day and 47.4 mg/day, respectively. Soy food and isoflavone intakes were not associated with 5-year changes in blood lipids or HbA1c concentrations. However, stratified analyses showed inverse associations between fermented soy intake and serum lipids among obese/overweight subjects. In particular, intake of 20 g/day of natto was associated with a reduction of 1.4 (95% CI 0.3, 2.5) mg/dL in TC, 1.5 (95% CI 0.4, 2.6) mg/dL in non-high-density lipoprotein cholesterol, 1.0 (95% CI − 0.0, 2.0) mg/dL in low-density lipoprotein cholesterol and 4.0 (95% CI 0.6, 7.5) mg/dL in triglycerides. Conclusions: Overall, habitual consumption of soy or isoflavones was not associated with changes in serum lipids or HbA1c concentrations. The negative associations between intake of natto and changes in serum lipids among overweight/obese subjects deserve further investigation. [ABSTRACT FROM AUTHOR]

Family history (FH) of cancer is an important factor of increased risk of several cancers. Although the association between FH of cancer and concordant cancer risk has been reported in many previous epidemiological studies, no comprehensive prospective study with adjustment for lifestyle habits has evaluated the association of FH of cancer and concordant cancer risk. We investigated the association between FH of cancer and concordant cancer risk in a Japanese population‐based prospective study, initiated in 1990 for cohort I and in 1993 for cohort II. We analyzed data on 103,707 eligible subjects without a history of cancer who responded to a self‐administered questionnaire including FH of cancer at baseline. Study subjects were followed through 2012 and analyzed using multivariable‐adjusted Cox proportional hazards regression models. During 1,802,581 person‐years of follow‐up, a total of 16,336 newly diagnosed cancers were identified. Any site (Hazard ratios = 1.11 (95% confidence interval = 1.07–1.15]), esophagus (2.11 [1.00–4.45]), stomach (1.36 [1.19–1.55]), liver (1.69 [1.10–2.61]), pancreas (2.63 [1.45–4.79]), lung (1.51 [1.14–2.00]), uterus (1.93 [1.06–3.51]) and bladder cancers (6.06 [2.49–14.74]) with FH of the concordant cancer were associated with an increased risk compared to those without FH. Our findings suggest that having FH of cancer is associated with an increased risk of several concordant cancer incidences in an Asian population. Enquiring about FH of several types of cancer may be important in identifying groups at high‐risk of those cancers. What's new? Although many epidemiological studies have reported an association between family history of cancer and concordant cancer risk, the association has not been evaluated in a comprehensive prospective study with adjustment for lifestyle habits. We found that a family history of cancer is associated with increased risk in the incidence of several concordant cancers in an Asian population. [ABSTRACT FROM AUTHOR]

Background An inverse association has been shown between dietary fiber intake and several noncommunicable diseases. However, evidence of this effect remains unclear in the Asian population. Objective We examined the association between dietary fiber intake and all-cause and cause-specific mortality, as well as the association between fiber intake from dietary sources and all-cause mortality. Methods We conducted a large-scale population-based cohort study (Japan Public Health Center-based prospective study). A validated questionnaire with 138 food items was completed by 92,924 participants (42,754 men and 50,170 women) aged 45–74 y. Dietary fiber intake was calculated and divided into quintiles. HR and 95% CI of total and cause-specific mortality were reported. Results During the mean follow-up of 16.8 y, 19,400 deaths were identified. In multivariable adjusted models, total, soluble, and insoluble fiber intakes were inversely associated with all-cause mortality. The HRs of total mortality in the highest quintile of total fiber intake compared with the lowest quintile were 0.77 (95% CI: 0.72, 0.82; P trend <0.0001) in men and 0.82 (95% CI: 0.76, 0.89; P trend <0.0001) in women. Increased quintiles of dietary fiber intake were significantly associated with decreased mortality due to total cardiovascular disease (CVD), respiratory disease, and injury in both men and women, whereas dietary fiber intake was inversely associated with cancer mortality in men but not women. Fiber from fruits, beans, and vegetables, but not from cereals, was inversely associated with total mortality. Conclusion In this large-scale prospective study with a long follow-up period, dietary fiber was inversely associated with all-cause mortality. Since intakes of dietary fiber, mainly from fruits, vegetables, and beans were associated with lower all-cause mortality, these food sources may be good options for people aiming to consume more fiber. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/objectives: Eating a variety of foods has been recommended in the dietary guidelines of many developed nations, as well as global dietary guidelines. We investigated the potential effect of dietary diversity on the risk of total mortality and major causes of mortality in a large-scale cohort study involving the Japanese population.Subjects/methods: From 1995 to 2012, 79,904 participants (37,240 men and 42,664 women) aged 45 to 74 years, without histories of ischemic heart disease, stroke, or cancer were followed-up for a median of 14.9 years. We used 133 food and beverage items listed on a 5-year follow-up food frequency questionnaire, and the daily frequency of consumption for each item (excluding five alcoholic beverages) was counted. Multivariable-adjusted Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to compare the highest and lowest quintiles.Results: An inverse association was identified between total dietary diversity and mortality rates in women (highest quintile HR: 0.81; 95% CI: 0.71, 0.92; p for trend = 0.002) but the same trend was not observed in men (highest quintile HR: 0.96; 95% CI: 0.87, 1.10; p for trend = 0.266). In addition, fruit diversity was associated with lower mortality rates in men (highest quintile HR: 0.87; 95% CI: 0.79, 0.95; p for trend = 0.006), whereas soy diversity was associated with lower mortality rates in women (highest quintile HR: 0.89; 95% CI: 0.79, 1.00; p for trend = 0.004). With regard to men, meat and fish diversity were associated with higher mortality rates (highest quintiles of meat and fish diversity HR: 1.15 [95% CI: 1.06, 1.25] and 1.12 [95% CI: 1.02, 1.22], respectively).Conclusions: These findings indicate that consuming a greater diversity of total foods and increasing the diversity of fruit and soy consumed have considerable public health implications. [ABSTRACT FROM AUTHOR]

Objective: While exposure to endogenous estrogen may be associated with better cognitive performance, it is still unclear whether it has an association with mild cognitive impairment (MCI) or dementia. The aim of this study was to clarify the effects of reproductive history, as a surrogate marker of exposure to endogenous estrogen, on the risk of cognitive impairment (MCI or dementia) in women.Study Design: A total of 747 women aged 40-59 years in the Saku area (Nagano Prefecture) were followed as part of the Japan Public Health Center-based Prospective (JPHC) Study, which started in 1990. Participants had undergone a mental health examination in 2014-2015.Main Outcome Measures: We used multiple logistic regression to analyze the association between reproductive history, obtained at baseline and 10-year follow-up, with current cognitive impairment diagnosed by a trained psychiatrist, adjusting for various lifestyle factors.Results: Among 670 eligible women, current cognitive impairment was diagnosed in 227, 196 of whom had MCI and 31 dementia. A longer reproductive period had a significantly inverse association with cognitive impairment (P-trend = 0.032). In particular, women with a reproductive period ≥38 years compared with ≤33 years had a significantly lower risk of cognitive impairment (multivariable adjusted odds ratio=0.62, 95% confidence interval=0.40-0.96).Conclusions: A longer reproductive period was associated with a lower risk of cognitive impairment, which suggests that a longer exposure to endogenous estrogen may have a protective effect against cognitive impairment. [ABSTRACT FROM AUTHOR]

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. Higher parity was associated with an increased risk of type 2 diabetes, and this association was attenuated after additional adjustment for BMI. This finding suggest that increased risk of type 2 diabetes associated with higher parity may be partly explained by increasing body weight. Other menstrual and reproductive factors was not associated with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: The obesity-lung cancer association remains controversial. Concerns over confounding by smoking and reverse causation persist. The influence of obesity type and effect modifications by race/ethnicity and tumor histology are largely unexplored.Methods: We examined associations of body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) with lung cancer risk among 1.6 million Americans, Europeans, and Asians. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for potential confounders. Analyses for WC/WHR were further adjusted for BMI. The joint effect of BMI and WC/WHR was also evaluated.Results: During an average 12-year follow-up, 23 732 incident lung cancer cases were identified. While BMI was generally associated with a decreased risk, WC and WHR were associated with increased risk after controlling for BMI. These associations were seen 10 years before diagnosis in smokers and never smokers, were strongest among blacks, and varied by histological type. After excluding the first five years of follow-up, hazard ratios per 5 kg/m2 increase in BMI were 0.95 (95% CI = 0.90 to 1.00), 0.92 (95% CI = 0.89 to 0.95), and 0.89 (95% CI = 0.86 to 0.91) in never, former, and current smokers, and 0.86 (95% CI = 0.84 to 0.89), 0.94 (95% CI = 0.90 to 0.99), and 1.09 (95% CI = 1.03 to 1.15) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Hazard ratios per 10 cm increase in WC were 1.09 (95% CI = 1.00 to 1.18), 1.12 (95% CI = 1.07 to 1.17), and 1.11 (95% CI = 1.07 to 1.16) in never, former, and current smokers, and 1.06 (95% CI = 1.01 to 1.12), 1.20 (95% CI = 1.12 to 1.29), and 1.13 (95% CI = 1.04 to 1.23) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Participants with BMIs of less than 25 kg/m2 but high WC had a 40% higher risk (HR = 1.40, 95% CI = 1.26 to 1.56) than those with BMIs of 25 kg/m2 or greater but normal/moderate WC.Conclusions: The inverse BMI-lung cancer association is not entirely due to smoking and reverse causation. Central obesity, particularly concurrent with low BMI, may help identify high-risk populations for lung cancer. [ABSTRACT FROM AUTHOR]

Smoking has been identified as a significant risk factor for acute myeloid leukaemia (AML). However, epidemiological evidence for the effect of smoking on the risk of AML among Asians is scarce. Here, we investigated the impact of smoking habits on the risk of AML by conducting a pooled analysis of 9 population-based prospective cohort studies in Japan. We analysed original data on smoking habits at baseline from 9 cohort studies. Hazard ratios (HRs) in the individual studies were calculated using a Cox proportional hazard model adjusted for potential confounders and combined using a random-effects model. During 4 808 175 person-years of follow-up for a total of 344 676 participants (165 567 men and 179 109 women), 245 AML cases (139 men and 106 women) were identified. For both sexes combined, current smokers had a marginally significant increased risk of AML compared to never smokers (HR = 1.44, 95% confidence interval [CI], 0.97-2.14). Ever smokers with more than 30 pack-years had a statistically significant increased risk of AML compared to never smokers among both sexes combined (HR = 1.66, 95% CI, 1.06-2.63). By sex, this significant association was observed only among men, with an HR of 1.69 (95% CI, 1.00-2.87) for ever smokers with more than 30 pack-years relative to never smokers. In conclusion, this study confirmed that cigarette smoking increases the risk of AML in Japanese. This study provides important evidence that smoking increases the risk of AML among Asians, which has already been shown in Western populations. [ABSTRACT FROM AUTHOR]

Background: Cruciferous vegetables, a rich source of isothiocyanates, have been reported to lower the risk of several types of cancer, including lung cancer. However, evidence from prospective observations of populations with a relatively high intake of cruciferous vegetables is sparse.Objective: We investigated the association between cruciferous vegetable intake and lung cancer risk in a large-scale population-based prospective study in Japan.Methods: We studied 82,330 participants (38,663 men; 43,667 women) aged 45-74 y without a past history of cancer. Participants were asked to respond to a validated questionnaire that included 138 food items. The association between cruciferous vegetable intake and lung cancer incidence was assessed with the use of Cox proportional hazard regression analysis to estimate HRs and 95% CIs (with adjustments for potential confounding factors).Results: After 14.9 y of follow-up, a total of 1499 participants (1087 men; 412 women) were diagnosed with lung cancer. After deleting early-diagnosed cancer and adjusting for confounding factors, we observed a nonsignificant inverse trend between cruciferous vegetable intake and lung cancer risk in men in the highest compared with the lowest quartiles (multivariate HR: 0.85; 95% CI: 0.69, 1.06; P-trend = 0.13). Stratified analysis by smoking status revealed a significant inverse association between cruciferous vegetable intake and lung cancer risk among those who were never smokers and those who were past smokers after deleting lung cancer cases in the first 3 y of follow-up [multivariate HR for never smokers: 0.49 (95% CI: 0.27, 0.87; P-trend = 0.04); multivariate HR for past smokers: 0.59 (95% CI: 0.35, 0.99; P-trend = 0.10)]. No association was noted in men who were current smokers and women who were never smokers.Conclusion: This study suggests that cruciferous vegetable intake may be associated with a reduction in lung cancer risk among men who are currently nonsmokers. [ABSTRACT FROM AUTHOR]

Evidence that diet is associated with breast cancer risk is inconsistent. Most of the studies have focused on risks associated with specific foods and nutrients, rather than overall diet. In this study, we aimed to evaluate the association between dietary patterns and breast cancer risk in Japanese women. A total of 49 552 Japanese women were followed-up from 1995 to 1998 (5-year follow-up survey) until the end of 2012 for an average of 14·6 years. During 725 534 person-years of follow-up, 718 cases of breast cancer were identified. We identified three dietary patterns (prudent, westernised and traditional Japanese). The westernised dietary pattern was associated with a 32 % increase in breast cancer risk (hazard ratios (HR) 1·32; 95 % CI 1·03, 1·70; Ptrend=0·04). In particular, subjects with extreme intake of the westernised diet (quintile (Q) Q5_5th) had an 83 % increase in risk of breast cancer in contrast to those in the lowest Q1 (HR 1·83; 95 % CI 1·25, 2·68; Ptrend=0·01). In analyses stratified by menopausal status, postmenopausal subjects in the highest quintile of the westernised dietary pattern had a 29 % increased risk of breast cancer (HR 1·29; 95 % CI 0·99, 1·76; Ptrend=0·04). With regard to hormone receptor status, the westernised dietary pattern was associated with an increased risk of oestrogen receptor-positive/progesterone receptor-positivetumours (HR 2·49; 95 % CI 1·40, 4·43; Ptrend<0·01). The other dietary patterns were not associated with the risk of breast cancer in Japanese women. A westernised dietary pattern is associated with an increased risk of breast cancer in Japanese women. [ABSTRACT FROM AUTHOR]

Background: Diet-induced metabolic acidosis has been linked to cardiometabolic abnormalities in Westerners, but the evidence on this issue is scarce in Asians.Objective: The present study prospectively examined the association between dietary acid load and type 2 diabetes (T2D) in Japanese adults.Methods: Study participants were 27,809 men and 36,851 women, aged 45-75 y, who completed a dietary questionnaire of the second survey of the Japan Public Health Center-based Prospective Study and had no previous history of T2D. Dietary intake was assessed by using a validated 147-item food-frequency questionnaire. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores were derived from the nutrient intake. A multilevel logistic regression model was used to estimate ORs and 95% CIs of self-reported, physician-diagnosed T2D over 5 y, with adjustment for potential confounding variables.Results: A total of 1191 cases of newly diagnosed T2D were reported. PRAL score was positively associated with T2D in men; the multivariable-adjusted ORs (95% CIs) for the lowest through the highest quartiles of PRAL were 1.00, 1.09 (0.87, 1.36), 1.10 (0.88, 1.37), and 1.25 (1.01, 1.55) (P-trend = 0.047). Further adjustment for dietary intake strengthened the association. NEAP score was not associated with the risk of T2D (P-trend = 0.20). In stratified analyses, the positive association between PRAL and T2D was confined to younger men (age <50 y; P-trend = 0.046). There was no association between dietary acid load score and T2D in women.Conclusion: A high dietary acid load score is associated with an increased risk of T2D in Japanese men. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was for the first time to assess the association between glycemic index (GI), glycemic load (GL), and colorectal cancer using a prospective Japanese population-based cohort.Methods: In our study participants aged 40-69 at baseline of the Japan Public Health Center-based prospective Study (JPHC Study) in 10 prefectural public health centers (PHC) were included. Subjects responding to the five-year follow-up survey (1995-1999) without previous history of cancer and missing data were included in the current analysis n = 73,501 (men n = 34,560 and women n = 38,941). We reported results as hazard ratios (HR) and 95% confidence intervals (CI) by Cox proportional hazards modeling.Results: The average follow-up time was 12.5 years (919,276 person-years). A total of 1,468 colorectal cancer cases were detected. Overall, no significant results were observed; however, GL was inversely nonsignificantly associated with colon cancer in men HR = 0.74 (95% CI 0.51-1.09) and rectal cancer in women 0.52 (95% CI 0.24-1.14). The GL tended to be inversely associated with proximal colon cancer among men 0.62 (95% CI 0.36-1.08), while a positive association with the GI was observed among women 1.37 (95% CI 0.88-2.14). Sensitivity analyses excluding the first three years of observation showed similar results. Results stratified by diabetes status, BMI, smoking and red meat were nonsignificant.Conclusions: In conclusion, the prospective JPHC Study suggests that the GI and GL do not have a substantial impact on the risk of colorectal cancer in Japanese adults. [ABSTRACT FROM AUTHOR]

Background: Recently, increased development of clinical prediction models has been reported in the medical literature. However, evidence synthesis methodologies for these prediction models have not been sufficiently studied, especially for practical situations such as a meta-analyses where only aggregated summaries of important predictors are available. Also, in general, the covariate sets involved in the prediction models are not common across studies. As in ordinary model misspecification problems, dropping relevant covariates would raise potentially serious biases to the prediction models, and consequently to the synthesized results.Methods: We developed synthesizing methods for logistic clinical prediction models with possibly different sets of covariates. In order to aggregate the regression coefficient estimates from different prediction models, we adopted a generalized least squares approach with non-linear terms (a sort of generalization of multivariate meta-analysis). Firstly, we evaluated omitted variable biases in this approach. Then, under an assumption of homogeneity of studies, we developed bias-corrected estimating procedures for regression coefficients of the synthesized prediction models.Results: Numerical evaluations with simulations showed that our approach resulted in smaller biases and more precise estimates compared with conventional methods, which use only studies with common covariates or which utilize a mean imputation method for omitted coefficients. These methods were also applied to a series of Japanese epidemiologic studies on the incidence of a stroke.Conclusions: Our proposed methods adequately correct the biases due to different sets of covariates between studies, and would provide precise estimates compared with the conventional approach. If the assumption of homogeneity within studies is plausible, this methodology would be useful for incorporating prior published information into the construction of new prediction models. [ABSTRACT FROM AUTHOR]