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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.
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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.
Subject(s)
Colorectal Neoplasms , Mutation , Proto-Oncogene Proteins B-raf , Receptors, Calcitriol , Vitamin D , Humans , Receptors, Calcitriol/genetics , Receptors, Calcitriol/metabolism , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/prevention & control , Male , Vitamin D/administration & dosage , Female , Middle Aged , Prospective Studies , Aged , Proto-Oncogene Proteins B-raf/genetics , Japan/epidemiology , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Diet , Proportional Hazards ModelsABSTRACT
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.
Subject(s)
Depression , Osteoporotic Fractures , Humans , Female , Middle Aged , Male , Aged , Japan/epidemiology , Prospective Studies , Adult , Depression/epidemiology , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/psychology , Osteoporotic Fractures/etiology , Incidence , Risk Factors , Longitudinal Studies , Hip Fractures/epidemiology , Hip Fractures/etiology , Follow-Up StudiesABSTRACT
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.
Subject(s)
Carbonated Beverages , Coffee , Depression , Fruit and Vegetable Juices , Tea , Humans , Female , Male , Carbonated Beverages/statistics & numerical data , Middle Aged , Depression/epidemiology , Adult , Cohort Studies , Sugar-Sweetened Beverages/statistics & numerical data , Sugar-Sweetened Beverages/adverse effects , Follow-Up Studies , AgedABSTRACT
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.
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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.
Subject(s)
Fatty Acids, Omega-3 , Fishes , Seafood , Shellfish , Stomach Neoplasms , Humans , Japan/epidemiology , Female , Prospective Studies , Male , Fatty Acids, Omega-3/administration & dosage , Stomach Neoplasms/epidemiology , Stomach Neoplasms/prevention & control , Middle Aged , Animals , Risk Factors , Seafood/analysis , Diet/methods , Diet/statistics & numerical data , Helicobacter Infections/epidemiology , Helicobacter Infections/complications , Aged , Adult , Helicobacter pylori , Proportional Hazards Models , Follow-Up StudiesABSTRACT
Accurate measurement of sodium intake in the diet is challenging, and epidemiological studies can be hampered by the attenuation of associations due to measurement error in sodium intake. A prediction formula for habitual 24-h urine sodium excretion and sodium-to-potassium ratio might lead to more reliable conclusions. Five 24-h urinary samples and two Food Frequency Questionnaires (FFQs) were conducted among 244 Japanese participants aged 35-80 years. We conducted multivariate linear regression analysis with urinary excretion as dependent variables and eating behaviour and food frequency as independent variables. Empirical weights of sodium excretion and sodium-to-potassium ratio were extracted. Preliminary validity was also assessed by randomly dividing the subjects into development and validation groups based on the correlation coefficient between estimates by the prediction formula and urinary excretion. Taste preference, soy sauce use at the table, frequency of pickled vegetables intake and number of bowls of miso soup were extracted as determinants of sodium excretion. Correlation coefficients between the estimates and urinary excretion for men and women were 0.42 and 0.43, respectively, for sodium and 0.49 and 0.50, respectively, for sodium-to-potassium ratio. This prediction formula may provide more accurate estimation of sodium intake and sodium-to-potassium ratio than the food composition approach.
Subject(s)
Potassium , Sodium , Humans , Female , Male , Middle Aged , Aged , Adult , Sodium/urine , Aged, 80 and over , Potassium/urine , Sodium, Dietary/urine , Sodium, Dietary/analysis , Feeding Behavior , Surveys and QuestionnairesABSTRACT
BACKGROUND: Genetic epidemiological evidence for the kidney function traits in East Asian population including Japanese remain still relatively unclarified. Especially, the number of GWASs for kidney traits reported still remains limited, and the sample size of each independent study is relatively small. Given the genetic variability between ancestries/ethnicities, implementation of GWAS with sufficiently large sample sizes in specific population of Japanese is considered meaningful. METHODS: We conducted the GWAS meta-analyses of kidney traits by leveraging the GWAS summary data of the representative large genome cohort studies with about 200,000 Japanese participants (n = 202,406 for estimated glomerular filtration rate [eGFR] and n = 200,845 for serum creatinine [SCr]). RESULTS: In the present GWAS meta-analysis, we identified 110 loci with 169 variants significantly associated with eGFR (on chromosomes 1-13 and 15-22; p < 5×10-8), whereas we also identified 112 loci with 176 variants significantly associated with SCr (on chromosomes 1-22; p < 5×10-8), of which one locus (more than 1Mb distant from known loci) with one variant (CD36 rs146148222 on chromosome 7) for SCr was considered as the truly novel finding. CONCLUSIONS: The present GWAS meta-analysis of largest genome cohort studies in Japanese provided some original genomic loci associated with kidney function in Japanese, which may contribute to the possible development of personalized prevention of kidney diseases based on genomic information in the near future.
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PURPOSE: Dietary fiber is a possible nutritional component which aids in the prevention of visceral fat accumulation. We examined the association between dietary fiber intake and visceral fat volume (VFV) by sex, and further analysed the association by major food sources of dietary fiber. METHODS: In this cross-sectional study, we measured VFV in 2779 Japanese (1564 men and 1215 women) aged 40-89 who underwent positron emission tomography/computed tomography for cancer screening between 2004 and 2005. Dietary fiber intake was calculated based on a validated semi-quantitative food frequency questionnaire. The association between dietary fiber intake and VFV was investigated using multivariate linear regression models after adjustment for potential confounders. RESULTS: Total, soluble, and insoluble fiber intakes were inversely associated with VFV in men (Q1: 3740 cm3, Q4: 3517 cm3, Ptrend: 0.0006 for total fiber), but not in women (Q1: 2207 cm3, Q4: 2193 cm3,Ptrend: 0.88 for total fiber). Statistically significant sex difference was observed (Pinteraction = 0.001 for total fiber). Subgroup analyses by major food sources revealed that dietary fiber intakes from beans, vegetables and fruits showed an inverse association with VFV in men, while cereal fiber intake showed a tendency toward a positive association in both sexes (Q1: 3520 cm3, Q4: 3671 cm3, Ptrend: 0.05 in men, Q1: 2147 cm3, Q4: 2227 cm3, Ptrend: 0.10 in women). CONCLUSION: We observed a sex-specific association between dietary fiber intake and VFV in Japanese adults. This study suggests that efforts against visceral fat accumulation should take account of the source of dietary fiber.
Subject(s)
Dietary Fiber , Intra-Abdominal Fat , Humans , Dietary Fiber/administration & dosage , Male , Female , Middle Aged , Cross-Sectional Studies , Aged , Japan , Adult , Sex Factors , Aged, 80 and over , Diet/methods , Diet/statistics & numerical data , Surveys and Questionnaires , Body Mass Index , East Asian PeopleABSTRACT
BACKGROUND: The mechanistic associations between obesity and risk of colorectal cancer (CRC) remain unclear. Here, using body mass index (BMI) as an obesity indicator, we decomposed the total effects of obesity on the risk of CRC into: (1) direct effects, which are possibly mediated by unmeasured or currently unknown factors; (2) indirect effects mediated by circulating leptin and adiponectin; and (3) indirect effects that are not mediated by circulating leptin and adiponectin but by hyperinsulinemia and chronic inflammation (assessed via circulating connecting peptide and C-reactive protein, respectively). METHODS: We adopted a causal mediation framework, using data from a large prospective cohort study of 44,271 Japanese men. RESULTS: BMI was not associated with the risk of CRC due to direct and indirect effects that were not mediated by circulating leptin and adiponectin. By contrast, individuals with BMIs of 25.0-27.4 kg/m2 (risk ratio, 1.29; 95% confidence interval, 0.98-1.69) and ≥27.5 kg/m2 (risk ratio, 1.28; 95% confidence interval, 0.98-1.68) had a higher risk of CRC due to indirect effects of circulating leptin and adiponectin. CONCLUSIONS: Our mediation analyses suggest that the association between BMI and CRC risk may be largely mediated by a pathway involving circulating leptin and adiponectin.
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Several studies have investigated the association between the use of anti-cholesterol drugs and cancer risks, of which results have been inconsistent. This study included 67,768 participants from the Japan Public Health Center-based Prospective Study. The data on anti-cholesterol drug use was collected using three questionnaires of the survey conducted every five years. We divided the participants into three groups according to the duration of the anti-cholesterol drug use. Multivariable-adjusted Cox proportional hazard regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). During the 893,009 person-years of follow-up from the 10-year follow-up survey, 8,775 participants (5,387 men and 3,388 women) were newly diagnosed with cancers. The duration of anti-cholesterol drug use was significantly associated with a decreased risk of liver cancer (HR:0.26, 95% CI 0.11-0.64 in > 5 y group) and with an increased risk of pancreatic cancer (HR:1.59, 95% CI 1.03-2.47 in > 5 y group). Moreover, a different trend was observed between men and women in the association with the risk of lung cancer. This study suggested that long-term use of anti-cholesterol drugs may have associations with a decreased incidence of liver cancer and with an increased incidence of pancreatic cancers.
Subject(s)
Liver Neoplasms , Pancreatic Neoplasms , Male , Humans , Female , Prospective Studies , Risk Factors , Japan/epidemiology , Pancreatic Neoplasms/epidemiology , Incidence , Proportional Hazards ModelsABSTRACT
Because of within-individual variation, surveys to estimate an individual's usual food intake must be conducted over many days, in general. Here, using non-invasive biomarkers, we examined the number of measurements required to screen for the usual intake of fruit and vegetables, in addition to sodium, potassium, and the sodium-to-potassium (Na/K) ratio. Participants were 202 subjects aged 40-74 years from five areas of Japan who completed weighed food records (WFR) and five 24-hour urinary collections (24-h UCs) between 2012 and 2013. The number of 24-h UCs required to screen for intake that deviated from guidelines estimated by the WFR and their accuracies were assessed by the area under the curve (AUC) in a receiver-operating characteristics (ROC) analysis. The single urinary excretion of sodium, potassium, and the Na/K ratio showed moderate performance (AUC value: >0.7) in discriminating deviations from their criteria by respective intake based on the WFR. Urinary potassium excretion also showed moderate performance (AUC value: >0.7) in estimating the intake of vegetables but could not be used to estimate fruit intake even after five collections. The non-invasive measurement of biomarkers in a single 24-h UC showed moderate performance in screening the usual intake of vegetables, as measured based on the 12-day WFR, as well as of sodium, potassium, and the Na/K ratio.
Subject(s)
Fruit , Vegetables , Humans , Sodium/urine , Diet , Potassium/urine , BiomarkersABSTRACT
OBJECTIVE: This population-based, cross-sectional study was performed to investigate the relationship between a history of glaucoma and subjective happiness. METHODS AND ANALYSIS: We conducted a cross-sectional questionnaire-based survey of 92 397 Japanese men and women aged 40-74 who participated in the Japan Public Health Center-based Prospective Study for the Next Generation study. A multivariable logistic regression model was used to estimate the ORs of glaucoma associated with subjective happiness and their two-sided 95% CIs. RESULTS: Among 40 727 men and 51 670 women, 1733 participants (635 men, 1098 women) had a history of glaucoma. The odds of unhappiness in male participants with a history of glaucoma were higher (OR 1.26; 95% CI 1.05 to 1.51) than in female participants (OR 1.05; 95% CI 0.90 to 1.23). In a subgroup analysis stratified by age, among participants with a history of glaucoma, males in the younger group (40-59 years) showed the most robust association with unhappiness (OR 1.40; 95% CI 1.04 to 1.88). CONCLUSIONS: These findings suggest that a history of glaucoma is related with subjective unhappiness, especially in men.
Subject(s)
Glaucoma , Happiness , Humans , Male , Female , Adult , Middle Aged , Cross-Sectional Studies , Prospective Studies , Surveys and Questionnaires , Glaucoma/epidemiologyABSTRACT
An East Asian-specific variant on aldehyde dehydrogenase 2 (ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci (GCKR, KLB, and ADH1B) in wild-type homozygotes and six (GCKR, ADH1B, ALDH1B1, ALDH1A1, ALDH2, and GOT2) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four (GCKR, ADH1B, ALDH1A1, and ALDH2) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-related disease risk.