Meat consumption and incident type 2 diabetes: an individual-participant federated meta-analysis of 1·97 million adults with 100 000 incident cases from 31 cohorts in 20 countries.

BACKGROUND: Meat consumption could increase the risk of type 2 diabetes. However, evidence is largely based on studies of European and North American populations, with heterogeneous analysis strategies and a greater focus on red meat than on poultry. We aimed to investigate the associations of unprocessed red meat, processed meat, and poultry consumption with type 2 diabetes using data from worldwide cohorts and harmonised analytical approaches. METHODS: This individual-participant federated meta-analysis involved data from 31 cohorts participating in the InterConnect project. Cohorts were from the region of the Americas (n=12) and the Eastern Mediterranean (n=2), European (n=9), South-East Asia (n=1), and Western Pacific (n=7) regions. Access to individual-participant data was provided by each cohort; participants were eligible for inclusion if they were aged 18 years or older and had available data on dietary consumption and incident type 2 diabetes and were excluded if they had a diagnosis of any type of diabetes at baseline or missing data. Cohort-specific hazard ratios (HRs) and 95% CIs were estimated for each meat type, adjusted for potential confounders (including BMI), and pooled using a random-effects meta-analysis, with meta-regression to investigate potential sources of heterogeneity. FINDINGS: Among 1 966 444 adults eligible for participation, 107 271 incident cases of type 2 diabetes were identified during a median follow-up of 10 (IQR 7-15) years. Median meat consumption across cohorts was 0-110 g/day for unprocessed red meat, 0-49 g/day for processed meat, and 0-72 g/day for poultry. Greater consumption of each of the three types of meat was associated with increased incidence of type 2 diabetes, with HRs of 1·10 (95% CI 1·06-1·15) per 100 g/day of unprocessed red meat (I2=61%), 1·15 (1·11-1·20) per 50 g/day of processed meat (I2=59%), and 1·08 (1·02-1·14) per 100 g/day of poultry (I2=68%). Positive associations between meat consumption and type 2 diabetes were observed in North America and in the European and Western Pacific regions; the CIs were wide in other regions. We found no evidence that the heterogeneity was explained by age, sex, or BMI. The findings for poultry consumption were weaker under alternative modelling assumptions. Replacing processed meat with unprocessed red meat or poultry was associated with a lower incidence of type 2 diabetes. INTERPRETATION: The consumption of meat, particularly processed meat and unprocessed red meat, is a risk factor for developing type 2 diabetes across populations. These findings highlight the importance of reducing meat consumption for public health and should inform dietary guidelines. FUNDING: The EU, the Medical Research Council, and the National Institute of Health Research Cambridge Biomedical Research Centre.

Mortality after partner's cancer diagnosis or death: A population-based prospective cohort study in Japan.

BACKGROUND: The health statuses of closely connected individuals are interdependent. Little is known about mortality risk associated with partner's cancer diagnosis and cause-specific mortality risk associated with partner's death. METHODS: Relative risks for all-cause and cause-specific mortality following a partner's cancer diagnosis or death compared to the period when the partner is cancer-free and alive were investigated in the population-based prospective cohort study that enrolled 140,420 people at the age between 40-69 in 1990-1994. RESULTS: 55,050 participants (27,665 men and 27,385 women) who were identified as married couples were followed-up for 1,073,746.1 (518,368.5 in men and 555,377.6 in women) person-years, during which 9,816 deaths (7,217 in men and 2,599 in women) were observed. After a partner's cancer diagnosis, the mortality rate ratio (MRR) of all-cause mortality was not increased among both men and women, while an increase of externally-caused MRR was observed. The suicide MRR significantly increased among men (MRR = 2.90 [95% CI, 1.70-4.93]) and it persisted for more than 5 years. After a partner's death, the MRRs of all-cause, cardiovascular disease (CVD), respiratory disease (RD), and externally-caused mortality significantly increased only among men. Stratified analysis by smoking status among men showed significantly increased MRRs of CVD and RD mortality among former/current smokers, but not among never-smokers. CONCLUSION: Partner's cancer diagnosis did not increase all-cause mortality risk, but increased externally-caused mortality risk, especially suicide among men. The impact of partner's death on mortality risk differed by the mortality causes and sex, and smoking affected some of cause-specific mortality risk.

Body Mass Index, Height and Head and Neck Cancer Risk: the Japan Public Health Center-based Prospective Study.

BACKGROUND: Although both a lower and a higher body mass index (BMI) are reportedly associated with head and neck cancer (HNC), reports from Asia are scarce. Moreover, evidence regarding the association between height and HNC is limited. METHODS: We investigated associations between BMI, height, and the incidence of HNC among 102,668 participants (49,029 men and 53,639 women) aged 40-69 years in the Japan Public Health Center-based Prospective Study. We followed participants from 1990 to 2013. We conducted a Cox proportional hazards regression analysis, which included adjustment for potential confounders such as smoking status. Baseline weight and height information were self-reported. RESULTS: Over an average follow-up of 18.7 years, 311 HNC cases were newly diagnosed. Lower BMI was significantly associated with HNC, with hazard ratios [HR] of 2.75 (95% confidence interval [CI]: 1.63-4.64) for <18.5 kg/m2 and 1.63 (95% CI=1.15-2.30) for 18.5-20.9 kg/m2 compared to 23-24.9 kg/m2. Increased risk was suggested for higher BMI, with an HR of 1.30 (95%CI=0.84-2.00) for ≥27.5 kg/m2. This trend was also observed in quadratic models. Results were similar among never smokers. Meanwhile, only lower BMI showed a strong association with HNC risk among former and current smokers (HR: 3.09, 95%CI: 1.54-6.20 for <18.5 kg/m2 compared to 23 to 24.9 kg/m2). Height showed no association with HNC. CONCLUSIONS: Lower BMI was significantly associated with HNC risk, while increased HNC risk was suggested in higher BMI among never smokers. Among former and current smokers, only lower BMI was associated with HNC risk.

Body Mass Index and Risk of Colorectal Cancer Incidence and Mortality in Asia.

Importance: The global burden of obesity is increasing, as are colorectal cancer (CRC) incidence and mortality. Objectives: To assess the association between body mass index (BMI) and risks of incident CRC and CRC-related death in the Asian population. Design, Setting, and Participants: This cohort study includes data pooled from 17 prospective cohort studies included in The Asia Cohort Consortium. Cohort enrollment was conducted from January 1, 1984, to December 31, 2002. Median follow-up time was 15.2 years (IQR, 12.1-19.2 years). Data were analyzed from January 15, 2023, through January 15, 2024. Exposure: Body mass index, calculated as weight in kilograms divided by height in meters squared. Main Outcomes and Measures: The primary outcomes were CRC incidence and CRC-related mortality. The risk of events is reported as adjusted hazard ratios (AHRs) and 95% CIs for incident CRC and death from CRC using the Cox proportional hazards regression model. Results: To assess the risk of incident CRC, 619 981 participants (mean [SD] age, 53.8 [10.1] years; 52.0% female; 11 900 diagnosed incident CRC cases) were included in the study, and to assess CRC-related mortality, 650 195 participants (mean [SD] age, 53.5 [10.2] years; 51.9% female; 4550 identified CRC deaths) were included in the study. A positive association between BMI and risk of CRC was observed among participants with a BMI greater than 25.0 to 27.5 (AHR, 1.09 [95% CI, 1.03-1.16]), greater than 27.5 to 30.0 (AHR, 1.19 [95% CI, 1.11-1.29]), and greater than 30.0 (AHR, 1.32 [95% CI, 1.19-1.46]) compared with those with a BMI greater than 23.0 to 25.0 (P < .001 for trend), and BMI was associated with a greater increase in risk for colon cancer than for rectal cancer. A similar association between BMI and CRC-related death risk was observed among participants with a BMI greater than 27.5 (BMI >27.5-30.0: AHR, 1.18 [95% CI, 1.04-1.34]; BMI >30.0: AHR, 1.38 [95% CI, 1.18-1.62]; P < .001 for trend) and was present among men with a BMI greater than 30.0 (AHR, 1.87 [95% CI, 1.49-2.34]; P < .001 for trend) but not among women (P = .15 for trend) (P = .02 for heterogeneity). Conclusions and Relevance: In this cohort study that included a pooled analysis of 17 cohort studies comprising participants across Asia, a positive association between BMI and CRC incidence and related mortality was found. The risk was greater among men and participants with colon cancer. These findings may have implications to better understand the burden of obesity on CRC incidence and related deaths in the Asian population.

Lifetime Risk of Incident Coronary Heart Disease, Stroke, and Cardiovascular Disease: The Japan Public Health Center-Based Prospective Study.

AIM: The constellation of cardiovascular disease (CVD) risk factors greatly impacts the lifetime risk (LTR) of incident CVD, but the LTR has not been thoroughly evaluated in the Japanese population. METHODS: We conducted a prospective study involving a total of 25,896 individuals 40-69 years old without a history of CVD in 1995 (Cohort I) and 1993-1994 (Cohort II) in Japan. CVD risk factors (blood pressure, non-high-density lipoprotein [HDL] cholesterol levels, smoking status, and glucose concentrations) were used to stratify them by risk. The sex-specific LTR of incident coronary heart disease, stroke, atherosclerotic CVD, and total CVD were estimated for participants 45 years old in the 4 risk categories with the cumulative incidence rate, adjusting for the competing risk of death. RESULTS: We found apparent differences in the LTR of total CVD according to the risk stratification. Individuals with ≥ 2 of the risk factors of blood pressure ≥ 140/90 mmHg or treated, non-HDL cholesterol level ≥ 170 mg/dL or treated, current smoker, and diabetes had substantially higher adjusted LTRs of CVD than those in other groups, with a LTR of 26.5% (95% confidence interval, 24.0%-29.0%) for men and 15.3% (13.1%-17.5%) for women at 45 years. The LTR of incident stroke was the highest among CVDs, and the presence of hypertension and diabetes mellitus strongly influenced the LTR of total CVD. CONCLUSION: The impact of risk accumulation on LTR of CVD was greater in men, and 1 in 4 men with ≥ 2 major risk factors at 45 years of age developed CVD in their lifetime.

Height, body mass index, physical activity, and risk of colorectal cancer in relation to expression of insulin receptor: The Japan Public Health Center-based Prospective Study.

To ascertain the involvement of insulin receptors (IRs) in colorectal carcinogenesis, we investigated the association of height, body mass index (BMI), and physical activity with colorectal cancer (CRC) and two subtypes of CRC according to the expression level of IR. We utilized data from a large-scale, population-based prospective cohort study of 18,158 middle-aged and elderly subjects in Akita and Okinawa, Japan. In the statistical analysis, we used the Cox proportional hazards model and estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CRC and its subtypes as defined by immunohistochemistry of IRß, a transmembrane subunit of IR. In the IRß-defined subtypes, height showed no apparent association with the risk of IRß-positive CRC. In contrast, a multivariable HR of IRß-positive CRC was 1.77 (95% CI = 1.04-3.03) with a BMI of ≥30.0 kg/m2 (i.e., obesity), compared to a BMI of <25.0 kg/m2. Further, an increase in physical activity was significantly associated with decreased risk of IRß-positive CRC (multivariable HR per 5 METs-hour/day = 0.93, 95% CI = 0.88-0.99). Meanwhile, we found no significant association between any exposure and IRß-negative CRC. Likewise, heterogeneity between the two subtypes of CRC was not statistically significant. These findings imply that obesity and physical activity exert promoting and suppressing effects on the development of CRC expressing IRs, respectively.

Serum anti­KIAA0513 antibody as a common biomarker for mortal atherosclerotic and cancerous diseases.

Numerous antibody biomarkers have been reported for cancer and atherosclerosis-related diseases. The major complications of atherosclerosis and diabetes mellitus (DM) are acute ischemic stroke (AIS), cardiovascular disease (CVD) and chronic kidney disease (CKD). Cancer development is accompanied by arterial disorders, such as angiogenesis and atherosclerosis, and DM is a risk factor for the development of certain types of cancer. Atherosclerosis-related diseases and cancers are therefore interrelated and could be detected using a common biomarker. In the present study, the initial screening using the protein array method identified KIAA0513 as an antigen recognized by serum IgG antibodies in patients with atherosclerosis. The amplified luminescent proximity homogeneous assay-linked immunosorbent assay revealed significantly higher serum antibody levels against recombinant KIAA0513 protein in patients with AIS, transient ischemic attack (TIA), DM, CVD, obstructive sleep apnea syndrome (OSAS), CKD and solid cancers, such as esophageal, gastric, colon, lung and breast cancers, compared with healthy donors. A receiver operating characteristic (ROC) analysis revealed that the highest areas under the ROC curves of anti-KIAA0513 antibodies were obtained for esophageal cancer, nephrosclerosis-type CKD and DM. Spearman's correlation analysis revealed that serum anti-KIAA0513 antibody levels were associated with maximum intima-media thickness and plaque score, which are indices of atherosclerosis and stenosis. Serum anti-KIAA0513 antibody markers appear to be useful for diagnosing AIS, TIA, DM, CVD, OSAS, CKD and solid cancers, and may reflect common arterial alterations leading to atherosclerotic and cancerous diseases.

Association Between Oral Malodor and Dementia: An 11-Year Follow-Up Study in Japan.

Background: As infrequent social interaction is a potential risk of dementia, oral malodor may increase the risk of dementia, including Alzheimer's disease. Objective: This study investigated the association between malodor and dementia. Methods: We used the Japan Public Health Center-based Prospective Study data obtained at Yokote City. A total of 1,493 individuals aged 56 to 75 years underwent a dental examination and self-reported survey from May 2005 to January 2006. Follow-up for the onset of dementia was conducted using long-term care insurance data from 2006 to 2016. Hazard ratios of oral malodor on dementia were estimated by the Cox proportional hazards model. The inverse probability-weighted Cox model was used as a sensitivity analysis. Results: The study comprised 1493 participants (53.6% women) with a mean age of 65.6 (SD = 5.8) years old; at the end of the follow-up, 6.4% (n = 96) developed dementia, and the percentage was 20.7 in severe malodor group. Throughout 15274.133 person-years of follow-up, the average incidence rate for the onset of dementia per 1000 person-years was 6.29. The highest incidence rate was seen in participants with severe malodor (22.4 per 1000 person-years). After adjusting for confounders, compared to those with no malodor, there was a 3.8 (95% confidence interval: 1.5 to 9.4) times greater hazard of developing dementia in participants with severe malodor. The inverse probability weighted Cox model confirmed the same trend with an adjusted marginal hazard ratio of 4.4 (1.2 to 16.4). CONCLUSIONS: A significant association between oral malodor and the onset of dementia exists.

Validity of self-reported participation in cancer screenings and health checkups in Japan.

BACKGROUND: The participation rate for screening is regarded as a useful indicator for preventing cancer and cardio-metabolic disease. However, the validity of self-reported screening participation has not yet been thoroughly evaluated in Japan. We aimed to examine its validity using the municipal screening records among the Japanese population. METHODS: We included 3,060 men and 3,860 women insured by the National Health Insurance for residents aged <75 years or the Medical Care System for the Elderly aged ≥75 years in the Chikusei area of the Japan Public Health Center-based Prospective Study for the Next Generation. They were asked about their participation in cancer screenings and health checkups during the previous year. We compared their responses to the municipal records and calculated the sensitivity and specificity of self-reported screening participation. RESULTS: The sensitivity and specificity of self-reported participation were 0.49 and 0.86 for lung cancer screening; 0.67 and 0.85 for colorectal cancer screening; 0.77 and 0.79 for stomach cancer screening; and 0.86 and 0.65 for health checkup, respectively. Among women, the sensitivity and specificity were 0.83 and 0.81 for breast cancer and 0.85 and 0.90 for cervical cancer, respectively. CONCLUSION: Self-reported cancer screening participation for colorectal, stomach, breast, and cervical cancers had moderate-high sensitivity and specificity. Self-reported participation, especially for lung cancer screening and health checkups, should be carefully interpreted when assessing the performance of preventive measures.

Dietary vitamin D intake and risk of colorectal cancer according to vitamin D receptor expression in tumors and their surrounding stroma.

BACKGROUND: Colorectal Cancer (CRC) has been molecularly classified into several subtypes according to tumor, stromal, and immune components. Here, we investigated whether the preventive effect of vitamin D on CRC varies with subtypes defined by Vitamin D receptor (VDR) expression in tumors and their surrounding stroma, along with the association of somatic mutations in CRC. METHODS: In a population-based prospective study of 22,743 Japanese participants, VDR expression levels in tumors and their surrounding stroma were defined in 507 cases of newly diagnosed CRC using immunohistochemistry. Hazard ratios of CRC and its subtypes according to dietary vitamin D intake were estimated using multivariable Cox proportional hazards models. RESULTS: Dietary vitamin D intake was not associated with CRC or its subtypes defined by VDR expression in tumors. However, an inverse association was observed for CRC with high VDR expression in the stroma (the highest tertile vs the lowest tertile: 0.46 [0.23-0.94], Ptrend = 0.03), but not for CRC with low VDR expression in the stroma (Pheterogeneity = 0.02). Furthermore, CRC with high VDR expression in the stroma had more somatic TP53 and BRAF mutations and fewer APC mutations than those with low VDR expression in the stroma. CONCLUSIONS: This study provides the first evidence that the preventive effect of vitamin D on CRC depends on VDR expression in the stroma rather than in the tumors. CRC with high VDR expression in the stroma is likely to develop through a part of the serrated polyp pathway, which tends to occur with BRAF but not with APC mutations.

Intake of Sugar and Food Sources of Sugar and Colorectal Cancer Risk in the Multiethnic Cohort Study.

BACKGROUND: The influence of sugar intake on the risk of colorectal cancer (CRC) remains controversial, and there is a need to investigate the heterogeneity of effects among racial and ethnic groups. OBJECTIVES: To examine the association of intake of simple sugars and their food sources with CRC risk according to race/ethnicity in a multiethnic cohort study. METHODS: We analyzed data from 192,651 participants who participated in the Multiethnic Cohort Study comprising African American, Japanese American, Latino, Native Hawaiian, and White older adults living in Hawaii and California with an average follow-up of 19 y. Intakes of total and specific types of sugars and sugary foods were estimated from a quantitative food frequency questionnaire completed by the participants in 1993-1996. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC risk according to quintiles (Q) of sugar and food intakes using Cox models adjusted for potential confounders. RESULTS: As of December 2017, 4403 incident CRC cases were identified. Among all participants, multivariable-adjusted CRC HRs for Q2, Q3, Q4, and Q5 compared with Q1 for total sugars were 1.03 (95% CI: 0.94, 1.13), 1.05 (95% CI: 0.96, 1.16), 1.12 (95% CI: 1.01, 1.24), and 1.13 (95% CI: 1.01, 1.27), respectively. A similar positive association was observed for total fructose, glucose, fructose, and maltose but not for added sugars and sugary foods. The increased risk appeared to be limited to colon cancer and to be strongest among younger participants (i.e., 45-54 y at baseline); an association with CRC was observed for sugar-sweetened beverages in the latter group. Among racial and ethnic groups, increased risk of CRC was most apparent in Latinos. CONCLUSIONS: In this diverse cohort, intakes of total sugar, total fructose, glucose, fructose, and maltose were associated with an increased risk of CRC, and the association was strongest for colon cancer, younger participants, and Latinos.

Association between fish and shellfish consumption, n-3 polyunsaturated fatty acids, and gastric cancer risk: the Japan Public Health Center-based Prospective Study.

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.

Plasma Albumin, Bilirubin, and Uric Acid and the Subsequent Risk of Cancer: A Case-Cohort Study in the Japan Public Health Center-based Prospective Study.

Several epidemiological studies have investigated the circulating levels of albumin, bilirubin, and uric acid (UA) in relation to cancer risk; however, they have provided equivocal evidence. In this prospective case-cohort study, we aimed to explore the association of plasma albumin, bilirubin, and UA levels with cancer incidence. We measured the plasma levels of albumin, bilirubin, and UA and investigated their association with cancer incidence in 3,584 cases and 4,270 randomly selected participants with a median follow-up of 15.8 years. The adjusted hazard ratios (HR) and 95% confidence intervals (CI) of total cancer for the highest (Q4) versus lowest quartile (Q1) was 0.77 (95% CI: 0.67-0.90, P for trend: <0.001) for albumin. This association was attenuated after excluding liver cancer cases with lower plasma albumin levels. Plasma bilirubin levels were positively related to liver cancer but inversely to total cancer after excluding liver cancer with adjusted HR Q4 vs. Q1 of 0.86 (95% CI: 0.74-0.99, P for trend = 0.015). Plasma UA levels were not dose-responsively associated with total cancer risk. Higher plasma bilirubin levels were associated with a decreased risk of total cancer after excluding liver cancer, which is likely attributed to the antioxidant properties of bilirubin.

Diabetes and gastric cancer incidence and mortality in the Asia Cohort Consortium: A pooled analysis of more than a half million participants.

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 < .01). Positive associations between diabetes and gastric cancer mortality were observed (HR 1.15, 95% CI 1.03-1.28) but attenuated after a 2-year time lag. CONCLUSION: Diabetes was associated with an increased gastric cancer incidence regardless of sex, anatomical subsite, or subtypes of gastric cancer. The risk of gastric cancer was particularly high during the first decade following diabetes diagnosis.

Association of sugary drinks, carbonated beverages, vegetable and fruit juices, sweetened and black coffee, and green tea with subsequent depression: A five-year cohort study.

BACKGROUND & AIMS: Evidence on the impact of beverage consumption on depression is limited in the Asian population. Specifically, there is little information available on vegetable and fruit juices, while whole vegetables and fruits are reportedly protective against depression. Furthermore, evidence is scarce in differentiating the impacts of sweetened and black coffee. We aimed to examine the association of the consumption of total sugary drinks, carbonated beverages, vegetable and fruit juices, sweetened and black coffee, and green tea with subsequent depression in a general population sample. METHODS: We studied individuals without a history of cancer, myocardial infarction, stroke, diabetes, or depression at baseline in 2011-2016, with a five-year follow-up. We used Poisson regression models and the g-formula, thereby calculating the risk difference (RD) for depression. Multiple sensitivity analyses were conducted. Missing data were handled using random forest imputation. We also examined effect heterogeneity based on sex, age, and body mass index by analyzing the relative excess risk due to interaction and the ratio of risk ratios. RESULTS: In total, 94,873 individuals were evaluated, and 80,497 completed the five-year follow-up survey for depression. Of these, 18,172 showed depression. When comparing the high consumption group with the no consumption group, the fully adjusted RD (95% CI) was 3.6% (2.8% to 4.3%) for total sugary drinks, 3.5% (2.1% to 4.7%) for carbonated beverages, 2.3% (1.3% to 3.4%) for vegetable juice, 2.4% (1.1% to 3.6%) for 100% fruit juice, and 2.6% (1.9% to 3.5%) for sweetened coffee. In contrast, the fully adjusted RD (95% CI) was -1.7% (-2.6% to -0.7%) for black coffee. The fully adjusted RD for green tea did not reach statistical significance. The results were robust in multiple sensitivity analyses. We did not find substantial effect heterogeneity based on sex, age, and body mass index. CONCLUSIONS: Total sugary drinks, carbonated beverages, vegetable and fruit juices, and sweetened coffee may increase the risk of depression, whereas black coffee may decrease it.

Association of depressive symptoms with incident fractures: the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT).

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.

Fruit and Vegetable Intake and Risk of Disabling Dementia: Japan Public Health Center Disabling Dementia Study.

BACKGROUND: Fruits and vegetables contain abundant amounts of antioxidant vitamins such as vitamin C, α-carotene, and ß-carotene. Few prospective observational studies have investigated the effects of fruit and vegetable intake on the risk of dementia, and the results are inconsistent. OBJECTIVES: Our aim was to examine associations between fruit and vegetable intake and the risk of disabling dementia. METHODS: We conducted a follow-up survey within the Japan Public Health Center-based Prospective Study involving 42,643 individuals aged 50-79 y at baseline (2000-2003). Dietary fruit and vegetable intakes and related antioxidant vitamin intakes (i.e., α-carotene, ß-carotene, and vitamin C) were determined using a food frequency questionnaire. The diagnosis of disabling dementia was made based on the daily living disability status related to dementia under the Japanese long-term care insurance program from 2006 to 2016. Hazard ratios and 95% confidence intervals for disabling dementia were estimated using area-stratified Cox proportional hazard models adjusted for potential confounding factors. RESULTS: A total of 4994 cases of disabling dementia were recorded. We observed an inverse association between total fruit and vegetable intake and the risk of dementia among males and females: the multivariate hazard ratios (95% confidence intervals) for the highest compared with lowest quartiles of intake were 0.87 (0.76, 0.99) (P- trend = 0.05) among males and 0.85 (0.76, 0.94) (P- trend = 0.006) among females. Among antioxidant vitamins, vitamin C intake was inversely associated with the risk of dementia among males and females: the multivariate hazard ratios (95% confidence intervals) for the highest compared with lowest quartiles of intake were 0.71 (0.61, 0.84) (P- trend < 0.0001) among males, and 0.76 (0.67, 0.86) (P- trend < 0.0001) among females. CONCLUSIONS: Fruit and vegetable intake and dietary intake of vitamin C may contribute to reducing the risk of disabling dementia among males and females.

Dietary Fiber Intake and Risk of Advanced and Aggressive Forms of Prostate Cancer: A Pooled Analysis of 15 Prospective Cohort Studies.

BACKGROUND: Evidence of an association between dietary fiber intake and risk of advanced and aggressive forms of prostate cancer (PC) and PC mortality is limited. OBJECTIVE: The aim of this study was to examine associations between intakes of dietary fiber overall and by food source and risk of advanced and aggressive forms of PC. DESIGN: The study design was a pooled analysis of the primary data from 15 cohorts in 3 continents. Baseline dietary fiber intake was assessed using a validated food frequency questionnaire or diet history in each study. PARTICIPANTS/SETTING: There were 842 149 men followed for up to 9 to 22 years between 1985 and 2009 across studies. MAIN OUTCOME MEASURES: The primary outcome measures were advanced (stage T4, N1, or M1 or PC mortality), advanced restricted (excluded men with missing stage and those with localized PC who died of PC), and high-grade PC (Gleason score ≥8 or poorly differentiated/undifferentiated) and PC mortality. STATISTICAL ANALYSIS PERFORMED: Study-specific multivariable hazard ratios (MVHR) were calculated using Cox proportional hazards regression and pooled using random effects models. RESULTS: Intake of dietary fiber overall, from fruits, and from vegetables was not associated with risk of advanced (n = 4863), advanced restricted (n = 2978), or high-grade PC (n = 9673) or PC mortality (n = 3097). Dietary fiber intake from grains was inversely associated with advanced PC (comparing the highest vs lowest quintile, MVHR 0.84; 95% CI 0.76-0.93), advanced restricted PC (MVHR 0.85; 95% CI 0.74-0.97), and PC mortality (MVHR 0.78; 95% CI 0.68-0.89); statistically significant trends were noted for each of these associations (P ≤ .03), and a null association was observed for high-grade PC for the same comparison (MVHR 1.00; 95% CI 0.93-1.07). The comparable results were 1.06 (95% CI 1.01-1.10; P value, test for trend = .002) for localized PC (n = 35,199) and 1.05 (95% CI 0.99-1.11; P value, test for trend = .04) for low/intermediate grade PC (n = 34 366). CONCLUSIONS: Weak nonsignificant associations were observed between total dietary fiber intake and risk of advanced forms of PC, high-grade PC, and PC mortality. High dietary fiber intake from grains was associated with a modestly lower risk of advanced forms of PC and PC mortality.

Active and passive smoking and breast cancer in Japan: a pooled analysis of nine population-based cohort studies.

BACKGROUND: Epidemiological studies have shown inconsistent results regarding the link between smoking and breast cancer risk, despite the biological plausibility of a positive association. METHODS: Participants were 166 611 women from nine prospective cohort studies in Japan which launched in 1984-1994 and followed for 8-22 years. Information on smoking and secondhand smoke was obtained through self-administered baseline questionnaires. Breast cancer was defined as code C50 according to the International Classification of Diseases for Oncology, 3rd Edition or the International Classification of Diseases, 10th Revision. After adjusting for several potential confounders, relative risks for breast cancer were calculated in the individual studies according to the current or previous status of active and passive smoking using Cox regression, followed by a summary estimate of hazard ratios using random-effects meta-analyses. RESULTS: Of the 60 441 participants who reported being premenopausal and 106 170 who reported being postmenopausal at baseline, 897 and 1168 developed breast cancer during follow-up, respectively. Compared with never smokers, current smokers had a higher risk of developing breast cancer before the age of 50 years. In addition, ever smokers who started smoking at 30 years of age or younger, or who started smoking before first childbirth, had a higher risk of developing breast cancer before the age of 50 years. No association between adulthood or childhood exposure to secondhand smoke and breast cancer was observed. CONCLUSION: Smoking may increase the risk of premenopausal breast cancer, and smoking earlier in life might be especially harmful. The impact of secondhand smoke needs further investigation.

Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium.

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust.