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Background: Genetic epidemiological evidence for the kidney function traits in East Asian populations, including Japanese, remain still relatively unclarified. Especially, the number of genome-wide association studies (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 1 Mb distant from known loci) with one variant (CD36 rs146148222 on chromosome 7) for SCr was considered as the truly novel finding. Conclusion: The present GWAS meta-analysis of the largest genome cohort studies in Japanese subjects provided some original genomic loci associated with kidney function, which may contribute to the possible development of personalized prevention of kidney diseases based on genomic information in the near future.

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

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

Abstract Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.

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

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.

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

Abstract Adult spinal deformity (ASD) is a complex condition that combines scoliosis, kyphosis, pain, and postoperative range of motion limitation. The lack of a scale that can successfully capture this complex condition is a clinical challenge. We aimed to develop a disease-specific scale for ASD. The study included 106 patients (mean age; 68 years, 89 women) with ASD. We selected 29 questions that could be useful in assessing ASD and asked the patients to answer them. The factor analysis found two factors: the main symptom and the collateral symptom. The main symptom consisted of 10 questions and assessed activity of daily living (ADL), pain, and appearance. The collateral symptom consisted of five questions to assess ADL due to range of motion limitation. Cronbach’s alpha was 0.90 and 0.84, respectively. The Spearman’s correlation coefficient between the change of main symptom and satisfaction was 0.48 (p

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

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

Abstract Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

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

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

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

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

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

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

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

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

Abstract Background Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. Methods We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes’ coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. Results In European ancestry samples, 14 genes were significantly associated (q

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

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

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

Abstract Aims/Introduction Among colorectal cancer (CRC) patients, pre‐existing diabetes is suggested to influence poor prognosis, but the impact on adjuvant chemotherapy implementation is largely unknown. We aimed to compare the implementation rate of adjuvant chemotherapy between CRC patients with and without pre‐existing diabetes in a retrospective cohort study. Materials and Methods Colorectal cancer diagnosis information was obtained from the hospital‐based cancer registry of patients with stage III CRC who underwent curative surgery in 2013 in Japan (n = 6,344). Health claims data were used to identify diabetes and chemotherapy. We examined the association between diabetes and the implementation rate of adjuvant chemotherapy using a generalized linear model adjusted for age, sex, updated Charlson Comorbidity Index, hospital type and prefecture. Furthermore, we applied a mediation analysis to examine the extent to which postoperative complications mediated the association. Results Of the 6,344 patients, 1,266 (20.0%) had diabetes. The mean ages were 68.2 and 71.3 years for patients without and with diabetes, respectively. Compared with those without diabetes, patients with diabetes were less likely to receive adjuvant chemotherapy (crude rate 58.9 and 49.8%; adjusted percentage point difference 4.6; 95% confidence interval 1.7–7.5). The difference was evident for patients aged

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

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

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

Abstract Background and Aim Chronic hepatitis C virus (HCV) infection, long‐term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene–environment interactions in HCC. To address genetic susceptibility to HCC, we conducted a genome‐wide association study (GWAS). Methods Two case‐control studies on HCC were conducted in the United States. DNA samples were genotyped using the Illumian microarray chip with over 710 000 single nucleotide polymorphisms (SNPs). We compared these SNPs between 705 HCC cases and 1455 population controls for their associations with HCC and verified our findings in additional studies. Results In this GWAS, we found that two SNPs were associated with HCC at P

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

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

Background: We designed a quick simple exercise program that can be performed in a short period of time in real-world occupational health settings and investigated the effects of three months of program implementation on non-specific low back pain (NSLBP). Methods: Participants were 136 individuals working in the manufacturing industry. The quick simple exercise program was designed to be doable in three minutes and consisted of two exercises: a hamstring stretch and a lumbar spine rotation with forward, backward, and lateral flexion. This was a randomized controlled trial incorporating an intervention group to whom the exercises were recommended within a leaflet, and a control group to whom the exercises were not recommended. NSLBP was evaluated at baseline and after three months using numerical rating scale (NRS) scores, ranging from 0 points (no pain at all) to 10 points (worst pain imaginable). The percentages of cases that improved by a minimal clinically important difference (two points or above) were compared. Results: Overall, 76.1% of the intervention group participants performed the quick simple exercises at least once every one or two days. Three months after baseline, a significantly higher percentage of participants in the intervention group (17 participants: 25%) had NSLBP improvement of two or more points on the NRS compared to that in the control group (8 participants, 12%) (P = 0.047). The average NRS score decreased significantly from 1.87 ± 1.86 to 1.33 ± 1.60 in the intervention group but showed no significant change in the control group, transitioning from 1.46 ± 1.73 to 1.52 ± 1.83. A significant interaction was also observed between the intervention and control groups (F = 6.550, P = 0.012). Conclusions: Three months of a quick simple exercise program among workers in the manufacturing industry increased the percentage of workers with improvement in the NRS scores. This suggests that the program is effective in managing NSLBP in workers in the manufacturing industry. Trial registration: UMIN-CTR UMIN000024117.

Introduction: Chronic low back pain (CLBP) is a leading cause of disability, yet there is limited high-quality evidence to identify the most suitable pharmacological therapy. The purpose of this Japanese nationwide, multicenter, prospective study was to compare the effectiveness of four representative drug therapies―acetaminophen, celecoxib, loxoprofen, and a tramadol and acetaminophen (T+A) combination drug―to establish evidence for a drug of choice for CLBP. Methods: Patients with CLBP (N=471) received one of the four treatments and were evaluated, prospectively and comprehensively, once every month for six months using a visual analog scale (VAS) for LBP, the Japanese Orthopedic Association (JOA) score, the JOA Back Pain Evaluation Questionnaire (JOABPEQ), the Roland-Morris Disability Questionnaire (RDQ), the EuroQol five-dimensions three-levels (EQ-5D-3L), and the Short Form-8 item health survey (SF-8). We conducted multivariable linear regression analyses of the four drugs at 1 and 6 months after drug allocation. Differences with P

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

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

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

Background: Short and long sleep durations are associated with mortality outcomes. The association between sleep duration and mortality outcomes may differ according to sex and age. Methods: Participants of the Japan Public Health Center-based prospective study (JPHC Study) were aged 40–69 years and had completed a detailed questionnaire on lifestyle factors. Sex- and age-stratified analyses on the association between habitual sleep duration and mortality from all-causes, cardiovascular diseases (CVD), cancer and other causes included 46,152 men and 53,708 women without a history of CVD or cancer. Cox proportional hazards regression models, adjusted for potential confounders, were used to determine hazard ratios and 95% confidence intervals. Results: Mean follow-up time was 19.9 years for men and 21.0 years for women. In the multivariable sex-stratified models, some categories of sleep durations ≥8 hours were positively associated with mortality from all-causes, CVD, and other causes in men and women compared with 7 hours. The sex- and age-stratified analyses did not reveal any major differences in the association between sleep duration and mortality outcomes in groups younger and older than 50 years of age. The only exception was the significant interaction between sleep duration and age in women for mortality from other causes. Conclusions: Sleep durations ≥8 hours are associated with mortality outcomes in men and women. Age may be an effect modifier for the association between sleep duration and mortality from other causes in women.

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

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

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

Polygenic risk scores predict the likelihood that an individual will develop a certain cancer, however these are often specific for a given population. Here, the authors show that a risk score developed to assess the risk of breast cancer in European women can also predict risk in Asian populations.

Introduction: Chronic low back pain (CLBP) is a major health burden worldwide and requires patient satisfaction with treatment. Consultation length can be an important factor in patient satisfaction, but few studies have investigated the impact of consultation length on satisfaction in patients with CLBP. This study tried to elucidate the impact of consultation length on clinical outcomes in patients with CLBP. Methods: This study is part of an analysis using the database of the nationwide, multicenter cohort for CLBP performed by the Project Committee of the Japanese Society for Spine Surgery and Related Research. A total of 427 patients aged 20-85 years (median age, 73.0 years; female, 58.6%) with CLBP were prospectively followed-up monthly for 6 months. Multivariable nonlinear regression analyses were performed to assess the effect of consultation length on outcome measures including subjective satisfaction score, EuroQol 5-dimension, Japanese Orthopaedic Association (JOA) score, Roland-Morris Disability Questionnaire, JOA Back Pain Evaluation Questionnaire, visual analog scale (VAS) and Medical Outcome Survey short-form 8-item health survey that evaluated at the next phase. Furthermore, we assessed whether the effect of consultation length on patient satisfaction was modified by the baseline Brief Scale for Psychiatric Problems in Orthopaedic Patients (BS-POP) score for patient and physician versions. Results: VAS for CLBP was the only score that correlated significantly with consultation length (P = 0.018). Satisfaction score showed a significant positive correlation with consultation length in patients with the highest baseline BS-POP scores (P < 0.2). Moreover, consultation lengths more than 7.6 min and 15.1 min offered increase of satisfaction if patients show the highest BS-POP scores on patient and physician versions, respectively. Conclusions: These findings suggest that a sufficiently long consultation is an important factor for subjective satisfaction in the patients with CLBP, particularly in patients with psychological problems.

Abstract Background Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by sleep apnea. Anoxia often occurs soon after birth, and it is important to prevent anoxia-mediated central nervous system complications; however, data on the relationship between respiratory management and the prognosis for intellectual development of patients with CCHS is not well yet investigate. Methods We performed a retrospective chart review cohort study of patients with CCHS in Japan. We investigated the risk and prognostic factors for developmental outcomes and examined the disease in terms of its symptoms, diagnosis, complications, and treatment. Results Of the 123 patients with CCHS included in the survey, 88 patients were 6 years old and older. They were divided into two group based on their intelligence quotient. Those treated using positive-pressure ventilation via tracheostomy in the first three months of life had a better developmental prognosis than those managed via tracheostomy after three months of age and those treated by ventilation using mask (OR = 3.80; 95% CI: 1.00–14.37, OR = 4.65; 95% CI: 1.11–19.37). There was no significant difference in physical development (P = 0.64). Conclusions The best respiratory treatment for patients with CCHS is ventilation via tracheostomy, initiated ideally before the age of three months.

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

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

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

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

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