Publications by authors named "Shoichiro Tsugane"

722 Publications

Dietary heterocyclic aromatic amine intake and cancer risk: epidemiological evidence from Japanese studies.

Genes Environ 2021 Jul 27;43(1):33. Epub 2021 Jul 27.

National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan.

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.
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http://dx.doi.org/10.1186/s41021-021-00202-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314635PMC
July 2021

Relation Between Body Mass Index and Dry Eye Disease: The Japan Public Health Center-Based Prospective Study for the Next Generation.

Eye Contact Lens 2021 Aug;47(8):449-455

Department of Ophthalmology (R.Y., A.H., M.U., M.K., K. Yuki, K. Tsubota), Keio University School of Medicine, Tokyo, Japan; Epidemiology and Prevention Group (R.Y., N.S., A.H., T.S., T.Y., A.G., M. Inoue, M. Iwasaki, S.T.), Center for Public Health Sciences, National Cancer Center, Tokyo, Japan; Center for Education and Educational Research (T.K.), Faculty of Education, Ehime University, Matsuyama, Japan; Department of Public Health and Epidemiology (I.S.), Faculty of Medicine, Oita University, Oita, Japan; Department of Public Health (K.A., S.M.), Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Department of Hygiene and Preventive Medicine (K. Tanno, K.S.), School of Medicine, Iwate Medical University, Iwate, Japan; Department of Public Health Medicine (K. Yamagishi, H.I.), Faculty of Medicine, and Health Services Research and Development Center, University of Tsukuba, Tsukuba, Japan; Ibaraki Western Medical Center (Kazumasa Yamagishi), Chikusei, Japan; Public Health (H.I.), Department of Social Medicine, Osaka University Graduate School of Medicine, Suita, Japan; and Department of Public Health (N.Y.), Kochi University Medical School, Kochi, Japan.

Objective: To investigate the relation between body mass index (BMI) and dry eye disease (DED).

Methods: We conducted a cross-sectional questionnaire-based survey in 85,264 Japanese men and women aged 40 to 74 years who participated in the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study). Dry eye disease was defined as the presence of severe symptoms or clinical diagnosis. A multivariable logistic regression model was used to estimate the odds ratios (ORs) of DED associated with BMI and their two-sided 95% confidence intervals (CIs). We adjusted for age, cohort area, visual display terminal time, smoking status, alcohol intake, education status, income status, as well as history of hormone replacement therapy for women.

Results: Prevalence of DED was 23.4% (n = 19,985; 6,289 men, 13,696 women). Higher BMI was correlated with a lower prevalence of DED in a dose-response fashion, with an adjusted OR of DED (95% CI) per 1 kg/m2 increment of BMI of 0.98 (95% CI: 0.97-0.99) for men and 0.97 (95% CI: 0.97-0.98) for women.

Conclusions: This large population-based study showed an inverse relationship between BMI and prevalence of DED in a Japanese population. Underestimation of DED is warned, especially for participants with high BMI.
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http://dx.doi.org/10.1097/ICL.0000000000000814DOI Listing
August 2021

Non-alcoholic beverages intake and risk of cardiovascular disease among Japanese men and women: the JPHC study.

Br J Nutr 2021 Jul 21:1-20. Epub 2021 Jul 21.

Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.

The association between the intake of non-alcoholic beverages and cardiovascular disease in Asians is uncertain. The intake of non-alcoholic beverages was estimated in 77,407 participants of the Japan public health center-based cohort study aged 45-74 years. The Cox regression calculated the HRs and 95% CIs for incident cardiovascular disease according to sex-specific quintiles of intake of non-alcoholic beverages. A total of 4578 incident cardiovascular disease (3,751 strokes and 827 coronary heart disease) were diagnosed during a 13.6-year median follow-up. The risks of stroke and total cardiovascular disease were lower for the highest versus lowest intake quintiles of non-alcoholic beverages in men and women: the multivariable HRs (95%CIs) were 0.82 (0.71-0.93, p-trend=0.005) and 0.86 (0.76-0.97, p-trend=0.02), respectively in men, and were 0.73 (0.63-0.86, p-trend=0.003) and 0.75 (0.65-0.87, p-trend=0.005) respectively in women. The reduced risk was evident for both ischemic and hemorrhagic strokes and was mainly attributable to green tea consumption. The intake of non-alcoholic beverages from coffee and other beverages was not associated with the risk of cardiovascular disease in both men and women. Also, there was no association between the intake of non-alcohol beverages and the risk of coronary heart disease in either sex. In conclusion, the risks of stroke and total cardiovascular disease were lower with a higher intake of non-alcoholic beverages in Japanese men and women.
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http://dx.doi.org/10.1017/S0007114521002737DOI Listing
July 2021

Validation study on diabetes definitions using Japanese Diagnosis Procedure Combination data among hospitalized patients.

J Epidemiol 2021 Jul 17. Epub 2021 Jul 17.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center.

BackgroundValidation studies on 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.MethodsWe 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.ResultsOf 72 patients, 23 were diagnosed with diabetes by 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: 66.9-98.7), 96.2% (87.0-99.5), 89.5% (66.9-98.7), and 96.2% (87.0-99.5), respectively, for (i) diabetes codes alone; 89.5% (66.9-98.7), 94.3% (84.3-98.8), 85.0% (62.1-96.8), and 96.2 (86.8-99.5) for (ii) diabetes codes and/or prescriptions; 68.4% (43.4-87.4), 100% (93.3-100), 100% (75.3-100), and 89.8% (79.2-96.2) for (iii) both diabetes codes and prescriptions.ConclusionsOur results suggest that DPC data can accurately identify diabetes among inpatients using (i) diabetes codes alone or (ii) diabetes codes and/or prescriptions.
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http://dx.doi.org/10.2188/jea.JE20210024DOI Listing
July 2021

Association of serum levels of antibodies against ALDOA and FH4 with transient ischemic attack and cerebral infarction.

BMC Neurol 2021 Jul 9;21(1):274. Epub 2021 Jul 9.

Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.

Background: Ischemic stroke, including transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI), is a serious health problem in the aging society. Thus, this study aimed to identify TIA and aCI biomarkers.

Methods: In 19 patients with TIA, candidate antigens recognized by serum IgG autoantibodies were screened using a human aortic endothelial cell cDNA library. Through amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), serum antibody levels against the candidate antigens were examined in healthy donor (HD), TIA, and aCI cohorts (n = 285, 92, and 529). The plasma antibody levels in the Japan Public Health Center-based Prospective Cohort Study (1991-1993) were also examined.

Results: The candidate antigens were aldolase A (ALDOA) and fumarate hydratase (FH). In AlphaLISA, patients with TIA or aCI had higher anti-ALDOA antibody (ALDOA-Ab) and anti-FH antibody (FH-Ab) levels than the HDs (P < 0.05). In a multivariate logistic regression analysis, the ALDOA-Ab (odds ratio [OR]: 2.46, P = 0.0050) and FH-Ab (OR: 2.49, P = 0.0037) levels were independent predictors of TIA. According to the case-control study, the ALDOA-Ab (OR: 2.50, P < 0.01) and FH-Ab (OR: 2.60, P < 0.01) levels were associated with aCI risk. In a correlation analysis, both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease, and habitual smoking. These antibody levels also correlated well with maximum intima-media thickness, which reflects atherosclerotic stenosis.

Conclusions: ALDOA-Abs and FH-Abs can be novel potential biomarkers for predicting atherosclerotic TIA and aCI.
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http://dx.doi.org/10.1186/s12883-021-02301-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268454PMC
July 2021

Validity of dietary isothiocyanate intake estimates from a food frequency questionnaire using 24 h urinary isothiocyanate excretion as an objective biomarker: the JPHC-NEXT protocol area.

Eur J Clin Nutr 2021 Jul 6. Epub 2021 Jul 6.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Background/objectives: Isothiocyanate (ITC) is formed via the hydrolysis of glucosinolates by myrosinase, found in cruciferous vegetables. Although myrosinase is inactivated by the cooking process, no studies have incorporated the effect of cooking into the estimation of dietary ITC intake or evaluated the validity. We evaluated the validity of dietary ITC intake estimated from a food frequency questionnaire (FFQ), and urinary ITC levels using 24 h urine samples or a WFR (weighed food record), and evaluated the reproducibility of dietary ITC in two FFQs administered at an interval of 1-year.

Subjects/methods: The JPHC-NEXT Protocol Area included a total of 255 middle-aged participants across Japan. We calculated dietary ITC intake from WFR and two FFQs by assuming that cooked cruciferous vegetables contain zero ITC. Urinary ITC excretion was measured at two points during summer and winter. The validity and reproducibility of dietary ITC intake estimated by FFQ were assessed using Spearman's correlation coefficients.

Results: Although we observed a moderate correlation between dietary ITC intake derived from a 12-day WFR and urinary ITC excretion, notwithstanding the cooking process, the correlation between dietary ITC intake estimated by FFQ and mean urinary ITC excretion was low. However, the correlation was improved when we compared urinary ITC excretion and a 3-day WFR or FFQ collected during winter. Our FFQ showed good reproducibility.

Conclusion: Although seasonality is a critical factor, dietary ITC intake estimated using an FFQ showed moderate validity and reproducibility and can be used in future epidemiological studies.
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http://dx.doi.org/10.1038/s41430-021-00970-xDOI Listing
July 2021

Exploratory research on determinants of place of death in a large-scale cohort study: the JPHC study.

J Epidemiol 2021 Jul 3. Epub 2021 Jul 3.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center.

BackgroundThe 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.MethodsA total of 17,546 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 by Japanese Vital Statistics. Adjusted odds ratios for home death were calculated by logistic regression.ResultsMultivariate analysis adjusted for various factors showed that unmarried status (OR 2.4, 95%CI:2.0-2.9), unemployed male (OR 1.3, 95%CI: 1.1-1.5), and high drinking level (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 in unmarried status stratified by cause of death (OR: cardiovascular 3.2, 95%CI:2.2-4.7 / cerebrovascular 5.0, 95%CI:2.8-8.9 / respiratory 3.4, 95%CI:1.6-7.6/ external 2.3, 95%CI:1.4-3.7), but for cancer, the risk of death at home tended to be higher in married status.ConclusionsThis study indicated 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.
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http://dx.doi.org/10.2188/jea.JE20210087DOI Listing
July 2021

Serum anti-AP3D1 antibodies are risk factors for acute ischemic stroke related with atherosclerosis.

Sci Rep 2021 Jun 29;11(1):13450. Epub 2021 Jun 29.

Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.

Atherosclerosis has been considered as the main cause of morbidity, mortality, and disability worldwide. The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning, which has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen. It was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke (AIS), transient ischemic attack, diabetes mellitus (DM), cardiovascular disease, chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were higher than those of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The results of the Japan Public Health Center-based Prospective Study indicated that this antibody marker is deemed useful as risk factors for AIS.
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http://dx.doi.org/10.1038/s41598-021-92786-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242008PMC
June 2021

The association between diabetes and gastric cancer: results from the Stomach Cancer Pooling Project Consortium.

Eur J Cancer Prev 2021 Jun 25. Epub 2021 Jun 25.

College of Public Health, University of South Florida, Tampa, Florida, USA Department of Clinical Sciences and Community Health, University of Milan, Milan Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy Department of Information Systems and Decision Sciences (ISDS), Muma College of Business, University of South Florida, Tampa, Florida, USA Department of Biomedical and Clinical Sciences, University of Milan, Milan Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network, ISPRO, Florence, Italy Department of Epidemiology, UCLA Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California, USA Department of Rehabilitation, Vinmec Hospital Times City, Vinmec Healthcare System Vietnam Colorectal Cancer and Polyps Research Program, Vinmec Healthcare System Department of Surgical Oncology, Viet-Duc University Hospital, Hanoi, Vietnam Medical Informatics Center, Peking University, Peking, China Department of Computer Sciences and Engineering, University of Nevada-Reno, Reno, Nevada Department of Public Health Sciences, Tobacco Center of Regulatory Science, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Japan Nikkei Disease Prevention Center, São Paulo, Brazil Department of Epidemiology and Prevention, Russian N.N. Blokhin Cancer Research Center, Moscow, Russia CIBER Epidemiología y Salud Pública (CIBERESP), Madrid ISGlobal IMIM (Hospital del Mar Medical Research Institute) Universitat Pompeu Fabra (UPF), Barcelona Environmental and Cancer Epidemiology Unit, National Center of Epidemiology, Carlos III Health Institute, Madrid, Spain Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore Department of Woman and Child Health and Public Health - Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia Department of Medicine, Memorial Sloan Kettering Cancer Centre, New York, NY, USA Department of Public and Community Health, School of Health Sciences, University of West Attica Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA Department of Public Health, Miguel Hernandez University, FISABIO-ISABIAL, Campus San Juan, Alicante, Spain Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA Centro Internacional de Pesquisa, A. C. Camargo Cancer Center, São Paulo, Brazil Departamento de Ciências da Saúde Pública e Forenses e Educação Médica, Faculdade de Medicina da Universidade do Porto, Al. Prof. Hernâni Monteiro EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, Porto, Portugal Stony Brook Cancer Center, Stony Brook University, New York, New York, USA Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background: Prior epidemiologic studies on the association between diabetes and gastric cancer risk provided inconclusive findings, while traditional, aggregate data meta-analyses were characterized by high between-study heterogeneity.

Objective: To investigate the association between type 2 diabetes and gastric cancer using data from the 'Stomach Cancer Pooling (StoP) Project', an international consortium of more than 30 case-control and nested case-control studies, which is large and provides harmonized definition of participants' characteristics across individual studies. The data have the potential to minimize between-study heterogeneity and provide greater statistical power for subgroup analysis.

Methods: We included 5592 gastric cancer cases and 12 477 controls from 14 studies from Europe, Asia, North America, and South America in a two-stage individual-participant data meta-analysis. Random-effect models were used to estimate summary odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) by pooling study-specific ORs.

Results: We did not find an overall association between diabetes and gastric cancer (pooled OR = 1.01, 95% CI, 0.94-1.07). However, the risk of cardia gastric cancer was significantly higher among individuals with type 2 diabetes (OR = 1.16, 95% CI, 1.02-1.33). There was no association between diabetes and gastric cancer risk in strata of Helicobacter pylori infection serostatus, age, sex, BMI, smoking status, alcohol consumption, fruit/vegetable intake, gastric cancer histologic type, and source of controls.

Conclusion: This study provides additional evidence that diabetes is unrelated to gastric cancer overall but may be associated with excess cardia gastric cancer risk.
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http://dx.doi.org/10.1097/CEJ.0000000000000703DOI Listing
June 2021

Body Mass Index, Height, Weight Change, and Subsequent Lung Cancer Risk: The Japan Public Health Center-Based Prospective Study.

Cancer Epidemiol Biomarkers Prev 2021 Jun 25. Epub 2021 Jun 25.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tsukiji, Chuo-ku, Tokyo, Japan.

Background: Body mass index (BMI) is inversely associated with lung cancer risk, while residual confounding by smoking or weight change is controversial. Evidence on height and lung cancer is scarce.

Methods: We investigated the associations between anthropometrics, BMI, and height, and incidence of lung cancer among 92,098 study subjects (44,158 men and 47,940 women) in the Japan Public Health Center-based Prospective Study. Cox proportional hazards regression was performed with adjustment for potential confounders and by cancer subtypes and smoking status. Information on weight and height was self-reported at baseline, and validated using measured health check-up data.

Results: During follow-up between 1990 and 2013 (average, 19.1 years), a total of 2,152 lung cancer cases were newly diagnosed. In a multivariate regression model, lower BMI was positively associated with overall lung cancer risk [<19 kg/m HR = 1.48; 95% confidence interval (CI) = 1.18-1.85 and 19-22.9 kg/m; HR = 1.19; 95% CI = 1.05-1.35; = <0.001] in men. The risk estimate was also elevated for adenocarcinoma in the BMI <19 kg/m category and for squamous cell carcinoma among men in the 19-22.9 kg/m BMI category. An association was also observed between low BMI, weight decrease, and squamous cell carcinoma in women. No significant associations were observed for other weight categories, height, weight change and lung cancer, adenocarcinoma, squamous and small cell carcinoma.

Conclusions: Our prospective study suggests that lower BMI may be associated with an increased risk of smoking-related lung cancer in Japan, irrespective of gender.

Impact: This study highlights the association between lower BMI and the risk of lung cancer in men.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0195DOI Listing
June 2021

Dietary glycemic index, glycemic load and mortality: Japan Public Health Center-based prospective study.

Eur J Nutr 2021 Jun 22. Epub 2021 Jun 22.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Purpose: Long-term associations of dietary glycemic index (GI) and glycemic load (GL) with mortality outcomes remain unclear.

Methods: The present analysis included 72,783 participants of the Japan Public Health Center-based Prospective Study. Participants who responded to the 5-year follow-up questionnaire in 1995-1999 were followed-up until December 2015. We estimated the risk of total and cause-specific mortality associated with GI and GL using Cox proportional hazards regression models.

Results: During 1,244,553 person years of follow-up, 7535 men and 4913 women died. GI was positively associated with all-cause mortality. As compared with the lowest quartile, the multivariable HR for those who had the highest quartile of GI was 1.14 (95% CI 1.08-1.20). The HRs for death comparing the highest with the lowest quartile were 1.28 (95% CI 1.14-1.42) for circulatory system diseases, 1.33 (95% CI 1.14-1.55) for heart disease, 1.32 (95% CI 1.11-1.57) for cerebrovascular disease, and 1.45 (95% CI 1.18-1.78) for respiratory diseases. GI was not associated with mortality risks of cancer and digestive diseases. GL showed a null association with all-cause mortality (highest vs lowest quartile; HR 1.04; 95% CI 0.96-1.12). However, among those who had the highest quartile of GL, the HRs for death from circulatory system diseases was 1.24 (95% CI 1.05-1.46), cerebrovascular disease was 1.34 (95% CI 1.03-1.74), and respiratory diseases was 1.35 (95% CI 1.00-1.82), as compared with the lowest quartile.

Conclusion: In this large prospective cohort study, dietary GI and GL were associated with mortality risks.
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http://dx.doi.org/10.1007/s00394-021-02621-0DOI Listing
June 2021

Serum anti-DIDO1, anti-CPSF2, and anti-FOXJ2 antibodies as predictive risk markers for acute ischemic stroke.

BMC Med 2021 Jun 9;19(1):131. Epub 2021 Jun 9.

Department of Endocrinology, Hematology and Gerontology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.

Background: Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS.

Methods: Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay.

Results: The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297-311 of DIDO1, 426-440 of FOXJ2, and 607-621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case-control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS.

Conclusions: Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.
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http://dx.doi.org/10.1186/s12916-021-02001-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188684PMC
June 2021

Validity of a food frequency questionnaire for the estimation of total polyphenol intake estimates and its major food sources in the Japanese population: the JPHC FFQ Validation Study.

J Nutr Sci 2021 11;10:e35. Epub 2021 May 11.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

We examine the validity and reproducibility of a food frequency questionnaire (FFQ) in a subsample of participants in the Japan Public Health Center-based Prospective Cohort Study using a database of polyphenol-containing foods commonly consumed in the Japanese population. Participants of the validation study were recruited from two different cohorts. In Cohort I, 215 participants completed a 28-d dietary record (DR) and the FFQ, and in Cohort II, 350 participants completed DRs and the FFQ. The total polyphenol intake estimated from the 28-d DR and FFQ were log-transformed and adjusted for energy intake by the residual method. Spearman correlation coefficients (CCs) between estimates from the FFQ and 28-d DR as well as two FFQs administered at a 1-year interval were computed. Median intakes of dietary polyphenols calculated from the DRs were 1172 mg/d for men and 1024 mg/d for women in Cohort I, and 1061 mg/d for men and 942 mg/d for women in Cohort II. The de-attenuated CCs for polyphenol intake between the DR and FFQ were 0⋅47 for men and 0⋅37 for women in Cohort I and 0⋅44 for men and 0⋅50 for women in Cohort II. Non-alcoholic beverages were the main contributor to total polyphenol intake in both men and women, accounting for 50 % of total polyphenol intake regardless of cohort and gender, followed by alcoholic beverages and seasoning and spices in men, and seasoning and spices, fruits and other vegetables in women. The present study showed that this FFQ had moderate validity and reproducibility and is suitable for use in future epidemiological studies.
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http://dx.doi.org/10.1017/jns.2021.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143878PMC
May 2021

Smoking cessation, weight gain and risk of cardiovascular disease.

Heart 2021 Jun 2. Epub 2021 Jun 2.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Objective: To examine whether the relationship between smoking cessation and risk of cardiovascular disease (CVD) was modified by weight gain.

Methods: A total of 69 910 participants (29 650 men and 46 260 women) aged 45-74 years were grouped into six groups by smoking status in the first and 5-year surveys: sustained smokers, recent quitters according to postcessation weight gain (no weight gain, 0.1-5.0 kg, >5.0 kg), long-term quitters and never smokers. Quitting smoking within and longer than 5 years were defined as recent and long-term quitters, respectively. We used Cox proportional hazard models to estimate the HR for incident CVD, coronary heart disease (CHD) and stroke.

Results: We identified 4023 CVDs (889 CHDs and 3217 strokes) during a median of 14.8 years of follow-up. Compared with sustained smokers, the multivariable HR (95% CI) for CVD was 0.66 (0.52 to 0.83) for recent quitters without weight gain, 0.71 (0.55 to 0.90) for recent quitters with weight gain of 0.1-5.0 kg, 0.70 (0.44 to 1.10) for recent quitters with weight gain of >5.0 kg, 0.56 (0.49 to 0.64) for long-term quitters, and 0.60 (0.55 to 0.66) for never smokers. The analysis restricted to men showed a similar association. Prespecified analysis by age suggested that recent quitters overall had a lower HR for CVD among those aged <60 years vs ≥60 years. Similar patterns of association were observed in CHD and stroke.

Conclusions: Postcessation weight gain did not attenuate the protective association between smoking cessation and risk of CVD.
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http://dx.doi.org/10.1136/heartjnl-2021-318972DOI Listing
June 2021

Effectiveness of screening using fecal occult blood test and colonoscopy on the risk of colorectal cancer: The Japan Public Health Center-based Prospective Study.

J Epidemiol 2021 May 29. Epub 2021 May 29.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center.

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 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 reduced by 44% in the subjects screened twice or thrice using FOBT (HR=0.56 95% 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.
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http://dx.doi.org/10.2188/jea.JE20210057DOI Listing
May 2021

Dietary glycemic index, glycemic load, and endometrial cancer risk: The Japan Public Health Center-based Prospective Study.

Cancer Sci 2021 May 30. Epub 2021 May 30.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Evidence supporting the association of glycemic index (GI) and glycemic load (GL) with the risk of endometrial cancer is controversial and reports from Asia were limited. Therefore, we aimed to investigate the association in Japanese women. We evaluated 52 460 women in the Japan Public Health Center-based Prospective Study aged 45-74 years who responded to the 5-year follow-up survey. GI and GL were calculated from a validated food frequency questionnaire, and the participants were divided into three groups by GI and GL. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with the Cox proportional hazard model adjusted for potential confounding factors. As a result, within 15.5 years of follow-up, 166 new cases of endometrial cancer were identified. Compared with the lowest GI and GL tertile groups, the HR of the risk of endometrial cancer in the highest GI tertile group was 0.80 (95% CI, 0.53-1.20; P  = .33), and that of the highest GL tertile group was 0.79 (95% CI, 0.52-1.19; P  = .82). The results were unchanged after stratification by body mass index, coffee consumption, and history of diabetes. In conclusion, we did not find any significant association between GI and GL with the risk of endometrial cancer. Further research is required to clarify the association.
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http://dx.doi.org/10.1111/cas.14997DOI Listing
May 2021

Reduction in total and major cause-specific mortality from tobacco smoking cessation: a pooled analysis of 16 population-based cohort studies in Asia.

Int J Epidemiol 2021 Feb 5. Epub 2021 Feb 5.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Little is known about the time course of mortality reduction following smoking cessation in Asians who have smoking behaviours distinct from their Western counterparts. We evaluated the level of reduction in all-cause, cardiovascular disease (CVD) and lung cancer mortality by years since quitting smoking, in Asia.

Methods: Using Cox regression, we analysed individual participant data (n = 709 151) from 16 prospective cohorts conducted in China, Japan, Korea/Singapore, and India/Bangladesh, separately by cohorts. Cohort-specific hazard ratios (HRs) were combined using a random-effects meta-analysis.

Results: During a mean follow-up of 12.0 years, 108 287 deaths were ascertained-35 658 from CVD and 7546 from lung cancer. Among Asian men, a dose-response relationship of risk reduction in deaths from all causes, CVD and lung cancer was observed with an increase in years after smoking cessation. Compared with never smokers, however, all-cause and CVD mortality among former smokers remained elevated 10-14 years after quitting [multivariable-adjusted HR (95% confidence interval (CI) = 1.25 (1.13-1.37) and 1.20 (1.02-1.41), respectively]. Lung cancer mortality stayed almost 2-fold higher than among never smokers 15-19 years after smoking cessation [1.97 (1.41-2.73)], particularly among former heavy smokers [2.62 (1.71-4.00)]. Women who quitted for ≥5 years retained a significantly elevated mortality from all causes, CVD and lung cancer. Overall patterns of the cessation-mortality associations were similar across countries.

Conclusions: Our findings suggest that adverse effects of tobacco smoking persist for an extended time period, even for more than two decades, which is beyond the time windows defined in current clinical guidelines for risk assessment of lung cancer and CVD.
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http://dx.doi.org/10.1093/ije/dyab087DOI Listing
February 2021

Exploring the interactions between Helicobacter pylori (Hp) infection and other risk factors of gastric cancer: A pooled analysis in the Stomach cancer Pooling (StoP) Project.

Int J Cancer 2021 Sep 24;149(6):1228-1238. Epub 2021 May 24.

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Helicobacter pylori (Hp) is crucial in gastric carcinogenesis, but infection alone is not a sufficient cause, and the interaction between Hp infection and other risk factors has not been adequately studied. We conducted a pooled analysis of seven case-control studies from the Stomach cancer Pooling (StoP) Project, comprising 1377 cases and 2470 controls, to explore the interaction among Hp infection and tobacco smoking, alcohol drinking, socioeconomic status (SES) and dietary salt intake on the risk of gastric cancer. We estimated summary odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by multivariate unconditional logistic regression. The analysis showed no consistent interaction between Hp infection and cigarette smoking, while interaction was more than multiplicative for alcohol drinking (OR = 1.38, 95% CI: 1.07-1.77, P-interaction 0.02) and high intake of salt (OR = 2.62, 95% CI: 1.88-3.65, P-interaction = 0.04). The interaction with SES followed the multiplicative model (P = 0.49), resulting in a weakening among infected individuals of the protective effect of high SES among observed Hp-negative individuals. The interactions found were more pronounced in subjects with history of peptic ulcer. The interactions with Hp infection were stronger for cigarette smoking and dietary salt in the case of noncardia cancer, and for alcohol and SES in the case of cardia cancer. No differences were found when stratifying for histologic type. This large-scale study aimed to quantify the interaction between Hp infection and other modifiable risk factors of gastric cancer revealed that the benefit of combined Hp eradication and lifestyle modification on gastric cancer prevention may be larger than commonly appreciated.
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http://dx.doi.org/10.1002/ijc.33678DOI Listing
September 2021

Prediagnostic circulating inflammation-related biomarkers and gastric cancer: A case-cohort study in Japan.

Cytokine 2021 Aug 10;144:155558. Epub 2021 May 10.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Gastric cancer is preceded by a chronic inflammatory process. Circulating levels of inflammation-related markers may reveal molecular pathways contributing to cancer development. Our study evaluated risk associations of gastric cancer with a wide range of systemic soluble inflammation and immune-response proteins. We performed a case-cohort analysis within the JPHC Study II, including a subcohort of 410 participants selected randomly within defined age and sex groups, and 414 individuals with incident gastric cancer. Ninety-two biomarkers were measured in baseline plasma using proximity extension assays. Gastric cancer multivariable hazard ratios were calculated for two to four quantiles used as ordinal variables of each biomarker by Cox proportional hazards regression models with age as the time metric. Of 73 evaluable biomarkers, three (CCL11, CCL20 and IL17C) were associated with increased gastric cancer risk and two (CCL23 and MMP1) with reduced cancer risk (P < 0.05). However, no association was statistically significant after a false discovery rate correction. This study largely expands the range of inflammation molecules evaluated for gastric cancer risk but failed to identify novel associations with this neoplasia.
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http://dx.doi.org/10.1016/j.cyto.2021.155558DOI Listing
August 2021

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies.

Am J Clin Nutr 2021 May 8. Epub 2021 May 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.

Background: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes.

Objective: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status.

Method: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models.

Results: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d).

Conclusion: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.
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http://dx.doi.org/10.1093/ajcn/nqab097DOI Listing
May 2021

Long-term response of Helicobacter pylori antibody titer after eradication treatment in middle-aged Japanese: JPHC-NEXT Study.

J Epidemiol 2021 Apr 28. Epub 2021 Apr 28.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center.

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 between 2011 and 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 one year (<1Y), one to five years (1-5Y), and more than six years ago (6Y+).

Results: Median serum antibody titer was 34.0 U/mL, 7.9 U/mL, 4.0 U/mL, and 2.9 U/mL for the Untreated, <1Y, 1-5Y, and 6Y+ groups, respectively. While those treated for H.pylori within the previous year had a 76.8% lower antibody titer compared to untreated subjects, approximately 41% of subjects were still seropositive.

Conclusions: A significant reduction in H.pylori antibody titer occurs within one year after eradication treatment, but that a long period is needed to achieve complete negative conversion.
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http://dx.doi.org/10.2188/jea.JE20200618DOI Listing
April 2021

Dietary Inflammatory Index Is Associated With Inflammation in Japanese Men.

Front Nutr 2021 9;8:604296. Epub 2021 Apr 9.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Dietary components are known to affect chronic low-grade inflammation status. The dietary inflammatory index (DII®) was developed to measure the potential impact of a diet on an individual's inflammatory status, and it has been validated mainly in Western countries. This study aimed to examine the validity of the energy-adjusted DII (E-DII) using high-sensitivity C-reactive protein (hs-CRP) concentration in Japanese men and women. In total, 6,474 volunteers from a cancer-screening program (3,825 men and 2,649 women) completed a food frequency questionnaire (FFQ) and their hs-CRP concentrations were evaluated. E-DII scores were calculated on the basis of 30 food parameters derived from the FFQ. Higher E-DII scores reflect a greater pro-inflammatory potential of the diet. The associations between E-DII quartiles and hs-CRP concentration were assessed using regression models adjusted for age, body mass index, smoking status, and amount of physical activity. Mean E-DII in men and women was + 0.62 ± 1.93 and -1.01 ± 2.25, respectively. The proportion of men and women who had hs-CRP concentration >3 mg/L was 4.7 and 3.1%, respectively. A significant positive association was observed between E-DII score and hs-CRP concentration in men; geometric mean of hs-CRP concentration in the lowest and highest E-DII quartiles was 0.56 mg/L and 0.67 mg/L ( < 0.01), respectively. The odds ratio (95% confidence interval) of having an elevated hs-CRP concentration (>3 mg/L) was 1.72 (1.10-2.67) in the highest E-DII quartile ( = 0.03) in men. However, no association was observed between E-DII score and hs-CRP concentration in women, except in those not taking prescription medications. DII was associated with inflammation status in Japanese men, but the association was limited in Japanese women.
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http://dx.doi.org/10.3389/fnut.2021.604296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062774PMC
April 2021

Body mass index and risk of recurrent falls in community-dwelling Japanese aged 40-74 years: The Murakami cohort study.

Geriatr Gerontol Int 2021 Jun 21;21(6):498-505. Epub 2021 Apr 21.

Department of Orthopaedic Surgery, Niigata University Medical and Dental Hospital, Niigata, Japan.

Aims: A prior meta-analysis found that obesity (body mass index [BMI] ≥ 30 kg/m ) was associated with a high fall risk, while being overweight (BMI≥25, <30 kg/m ) was associated with the lowest fall risk. However, whether these associations hold true for East Asians is unknown. This study aimed to assess the association between BMI and incidence of recurrent falls in Japanese aged 40-74 years.

Methods: This 5-year follow-up cohort study involved 7538 community-dwelling individuals who did not experience recurrent falls in the year before the baseline study. Information on demographics, body size, lifestyle, and disease history was obtained using a self-administered questionnaire. BMI was categorized as <18.5 (underweight), 18.5-20.6 (low-normal), 20.7-22.7 (mid-normal, reference), 22.8-24.9 (high-normal), and ≥ 25.0 kg/m (overweight). The outcome was recurrent falls reported, and fall history in the previous year was recorded as none, once, or twice or more (recurrent falls).

Results: Mean BMI was 23.5 kg/m (SD 2.9) for men and 22.7 kg/m (SD 3.2) for women. The adjusted odds ratio (OR) for recurrent falls in the BMI ≥25 group was significantly higher (1.41, 95%CI: 1.02-1.93) than that in the reference group. The adjusted OR in the BMI ≥25 group was significantly higher than that in the reference group for the age ≥ 60 subgroup (1.62, 95%CI: 1.09-2.40), but not for the age < 60 subgroup (OR = 1.04, 95%CI: 0.60-1.80).

Conclusions: Being overweight may be a risk factor for recurrent falls in community-dwelling older Japanese. Further studies are needed to determine the underlying mechanism. Geriatr Gerontol Int 2021; 21: 498-505.
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http://dx.doi.org/10.1111/ggi.14167DOI Listing
June 2021

Association of sugary drink consumption with all-cause and cause-specific mortality: the Japan Public Health Center-based Prospective Study.

Prev Med 2021 07 15;148:106561. Epub 2021 Apr 15.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Background: Few epidemiologic studies have assessed the associations of sugary drink consumption with mortality outcomes among Asian populations.

Methods: This study included 70,486 participants in the Japan Public Health Center-based Prospective Study at the age of 45-74 years in 1995-1999. A validated food frequency questionnaire was used to assess the consumption of sugary drinks. We estimated the risk of total and cause-specific mortality associated with sugary drink consumption using Cox proportional hazards regression model.

Results: Mean follow-up was 17.1 years, during which 11,811 deaths were documented. Sugary drink consumption was associated with higher total mortality, with multivariate HR of 1.06 (95% CI 1.00-1.13) for quintile 3, 1.07 (95% CI 1.01-1.13) for quintile 4, and 1.15 (95% CI 1.09-1.22) for quintile 5, compared with quintile 1 (P < 0.001 for trend). Additionally, positive associations with cause-specific mortality were observed, including death from circulatory system diseases (quintile 5 vs quintile 1; HR, 1.23; 95% CI 1.09-1.38) and heart disease (quintile 5 vs quintile 1; HR, 1.35; 95% CI 1.14-1.60).

Conclusion: In this large Japanese prospective study, sugary drink consumption was associated with all-cause and cause-specific mortality.
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http://dx.doi.org/10.1016/j.ypmed.2021.106561DOI Listing
July 2021

Association Between Birth Weight and Risk of Pregnancy-Induced Hypertension and Gestational Diabetes in Japanese Women: JPHC-NEXT Study.

J Epidemiol 2021 Apr 13. Epub 2021 Apr 13.

Epidemiology and Prevention Group, Center for Public Health and Sciences, National Cancer Center.

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 <1,500 grams (adjusted odd ratio [aOR] 1.60; 95% confidence interval [CI], 1.17-2.21), 1,500-2,499 grams (aOR 1.16; 95% CI, 1.03-1.30), and 2,500-2,999 grams (aOR 1.13; 95% CI, 1.04-1.22). The risk of GDM was significantly higher among women born 1,500-2,499 grams (aOR 1.20; 95% CI, 1.02-1.42), albeit non-significant association among women in other birthweight categories.

Conclusions: We observed an increased risk of PIH among women born with lower birth weight albeit non-significant increased risk of GDM among Japanese women.
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http://dx.doi.org/10.2188/jea.JE20200302DOI Listing
April 2021

Relationship between unhealthy sleep status and dry eye symptoms in a Japanese population: The JPHC-NEXT study.

Ocul Surf 2021 Apr 17. Epub 2021 Apr 17.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Purpose: To investigate whether and how unhealthy sleep habits (i.e., the frequency of difficulty falling or staying asleep, and the frequency of waking up tired) and the duration of sleep are related to the prevalence of dry eye disease (DED) in a general population.

Methods: This study included a total of 106,282 subjects aged 40-74 years who participated in a baseline survey of the Japan Public Health Center-based Prospective Study for the Next Generation. DED was defined as the presence of clinically diagnosed DED or severe symptoms. Multivariable-adjusted logistic regression models were used to assess the relationships of various components of sleep status with DED.

Results: Higher frequencies of having difficulty falling or staying asleep, and waking up tired were significantly related to increased DED in both sexes (P<0.001). Compared with those with 8 h/day of sleep, shorter sleepers had an increased prevalence of DED in both sexes, although DED was increased among men who slept ≥10 h/day. By comparing participants with the greatest vs. the least difficulty of falling asleep, the multivariable-adjusted odds ratios (95% confidence interval [CI]) were 2.23 (95% CI, 1.99-2.49) for men and 1.91 (95% CI, 1.76-2.07) for women. When analyzed separately, the magnitude of each relationship was stronger with severe DED symptoms than with clinically diagnosed DED.

Conclusions: Sleep deprivation and poor sleep quality were significantly related to DED in a Japanese population.
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http://dx.doi.org/10.1016/j.jtos.2021.04.001DOI Listing
April 2021

Reproductive Factors and Lung Cancer Risk among Never-Smoking Japanese Women with 21 Years of Follow-Up: A Cohort Study.

Cancer Epidemiol Biomarkers Prev 2021 Jun 7;30(6):1185-1192. Epub 2021 Apr 7.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Background: Previous studies have reported inconsistent associations between reproductive factors and lung cancer.

Methods: We used data from the Japan Public Health Center-based Prospective Study, which included 400 incident lung cancer cases (305 adenocarcinoma) among 42,615 never-smoking women followed for a median of 21 years, to examine the associations of reproductive and hormonal factors with lung cancer by histological type using Cox proportional hazards models.

Results: Longer fertility span (≥36 years vs. ≤32 years) was associated with increased risk of lung adenocarcinoma (HR, 1.48; 95% CI, 1.07-2.06, = 0.01) but not with all lung cancer or nonadenocarcinoma. Similarly, late age at menopause (≥ 50 years) was associated with increased adenocarcinoma risk (vs. ≤ 47 years, HR, 1.41; 95% CI, 1.01-1.96, 0.04). Compared with premenopausal women, women with natural menopause (HR, 1.99; 95% CI, 1.02-3.88) or surgical menopause (HR, 2.75; 95% CI, 1.33-5.67) were at increased risk of adenocarcinoma. In contrast, breastfeeding was associated with reduced risk of nonadenocarcinoma (HR, 0.51; 95% CI, 0.28-0.92). No significant association with parity, age at first birth, exogenous hormone use, or length of menstrual cycle was detected.

Conclusions: Reproductive factors may play a role in lung carcinogenesis. Future studies that include estrogen and progesterone biomarkers may help clarify the role of endogenous hormones in lung carcinogenesis.

Impact: Fertility span and age at menopause may be useful variables in developing risk prediction models for lung adenocarcinoma among nonsmoking women.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1399DOI Listing
June 2021

Effectiveness of a Cancer Risk Prediction Tool on Lifestyle Habits: A Randomized Controlled Trial.

Cancer Epidemiol Biomarkers Prev 2021 Jun 26;30(6):1063-1071. Epub 2021 Mar 26.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, Japan.

Background: Risk prediction models offer a promising approach to lifestyle modification. We evaluated the effect of personalized advice based on cancer risk prediction in improving five lifestyle habits (smoking, alcohol consumption, salt intake, physical activity, and body mass index) compared with standard advice without risk prediction among a Japanese general population with at least one unhealthy lifestyle habit.

Methods: In a parallel-design, single-blind, randomized controlled trial between February 2018 and July 2019, 5984 participants aged 40-64 years with unhealthy lifestyle habits were recruited from persons covered under a life insurance policy. They were randomly assigned to an intervention or control group and received personalized or standard advice, respectively. They were also sent an invitation to participate in a lifestyle modification program aimed at improving lifestyle. Primary outcome was an improvement in lifestyle, defined as an increase in healthy lifestyle habits within 6 months.

Results: The proportion of participants who improved their lifestyle within 6 months in the intervention group did not significantly differ from that in the control group (18.4% vs. 17.7%; = 0.488). Among participants with low health literacy and two or fewer of five healthy habits, the proportion of participants subscribing to the lifestyle modification program was higher in the intervention group than in the control group.

Conclusions: Compared with standardized advice, personalized advice based on cancer risk prediction had no effect on improving lifestyle.

Impact: Provision of predicted cancer risk information did not induce change in unhealthy lifestyle.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1499DOI Listing
June 2021

Weight change during middle age and risk of stroke and coronary heart disease: The Japan Public Health Center-based Prospective Study.

Atherosclerosis 2021 04 23;322:67-73. Epub 2021 Feb 23.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Background And Aims: The impact of weight changes in middle age on the incidence of cardiovascular disease has not been well elucidated. We investigated whether a 5-year weight change was associated with risk of stroke and coronary heart disease (CHD) in middle-aged individuals.

Methods: We analyzed data of 74,928 participants aged 40-69 years who provided responses to the baseline and 5-year follow-up questionnaires in the Japan Public Health Center-based Prospective Study. Weight change was calculated by subtracting self-reported weight at baseline from that at 5-year follow-up. Stroke and CHD events were confirmed by reviewing hospital records.

Results: During 997,406 person-years of follow-up, we documented 3,975 stroke and 914 CHD events. The multivariable HRs of stroke for losing ≥5 kg compared to stable weight (change ≤2 kg) was 1.17 (95% CI, 1.01-1.37) in men versus 1.33 (1.13-1.57) for losing ≥5 kg and 1.61 (1.36-1.92) for gaining ≥5 kg in women (U-shaped association). These associations did not change after the exclusion of early events. The multivariable HR of CHD for gaining ≥5 kg was 1.22 (0.95-1.58) in men. After exclusion of early events within another 5 years, that positive association became stronger [multivariable HR 1.34 (1.00-1.82)].

Conclusions: Weight gain during middle age was associated with an increased risk of stroke in women and an increased risk of CHD in men. Weight loss was associated with an increased risk of stroke in both men and women.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.02.017DOI Listing
April 2021
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