Publications by authors named "Kenji Wakai"

421 Publications

Nutritional Influences on Locomotive Syndrome.

J Clin Med 2022 Jan 26;11(3). Epub 2022 Jan 26.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.

Healthy dietary habits are important to prevent locomotive syndrome (LS). We investigated the relationship between LS and nutritional intake using community health checkup data. We included 368 participants who underwent LS staging, blood sampling, and nutritional intake assessments. Participants (163 adults < 65: 205 older adults ≥ 65) were divided into normal (N; LS stage 0) and LS (L; LS stage 1-2) groups, and blood sample data and nutritional intake were compared between groups. Among adults (N group, 71; L group, 92), low-density lipoprotein cholesterol (LDL-C) was significantly lower, and Vitamin B intake was significantly higher in the L than in the N group; LDL-C, = 0.033; Vitamin B1, 0.029. Among older adults (N group, 85; L group, 120), hemoglobin (Hb), albumin, and calcium levels were significantly lower, and sodium, monounsaturated fatty acids (MUFA), and n-6 polyunsaturated fatty acids (n-6 PUFA) were significantly higher in the L than the N group; Hb, = 0.036; albumin, 0.030; calcium, 0.025; sodium; 0.029; MUFA; 0.047, n-6 PUFA; 0.0233). Logistic regression analysis indicated that sodium was the risk factor for the L group (exp (B) 1.001, 95% CI: 1-1.001, = 0.032). In conclusion, salt intake was associated with LS.
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http://dx.doi.org/10.3390/jcm11030610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836534PMC
January 2022

A genome-wide association study on adherence to low-carbohydrate diets in Japanese.

Eur J Clin Nutr 2022 Feb 7. Epub 2022 Feb 7.

Department of Preventive Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.

Background/objectives: Low-carbohydrate diets (LCD) are useful for weight reduction, and 50-55% carbohydrate consumption is associated with minimal risk. Genetic differences were related to nutritional consumption, food preferences, and dietary patterns, but whether particular genetic differences in individuals influence LCD adherence is unknown.

Subjects/methods: We conducted a GWAS on adherence to LCD utilizing 14,076 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a previously validated semiquantitative food frequency questionnaire to estimate food consumption. Association of the imputed variants with the LCD score by Halton et al. we used linear regression analysis adjusting for sex, age, total dietary energy consumption, and components 1 to 10 by principal component analysis. We repeated the analysis with adjustment for alcohol consumption (g/day) in addition to the above-described variables.

Results: Men and women combined analysis without adjustment for alcohol consumption; we found 395 variants on chromosome 12 associated with the LCD score having P values <5 × 10. A conditional analysis with the addition of the dosage data of rs671 on chromosome 12 as a covariate, P values for all 395 SNPs on chromosome 12 turned out to be insignificant. In the analysis with additional adjustment for alcohol consumption, we did not identify any SNPs associated with the LCD score.

Conclusion: We found rs671 was inversely associated with adherence to LCD, but that was strongly confounded by alcohol consumption.
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http://dx.doi.org/10.1038/s41430-022-01090-wDOI Listing
February 2022

Investigation of miRNA expression profiles using cohort samples reveals potential early detectability of colorectal cancers by serum miR-26a-5p before clinical diagnosis.

Oncol Lett 2022 Mar 21;23(3):87. Epub 2022 Jan 21.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.

Previous studies have investigated the usefulness of microRNA (miRNA/miR) expression data for the early detection of colorectal cancer (CRC). However, limited data are available regarding miRNAs that detect CRC before clinical diagnoses. Accordingly, the present study investigated the early detectability of CRC by miRNAs using the preserved serum samples of the cohort participants affected with CRC within 2 years of study enrollment. First, the significant miRNAs were revealed using clinical CRC samples for a (seven early CRCs and seven controls) microarray analysis based on significance analysis of microarrays. Next, replicability was verified by reverse transcription-quantitative (RT-q)PCR (eight early CRCs and eight controls, together with 12 CRCs and 12 controls). Finally, early detectability was tested using the cohort samples of Japan Multi-Institutional Collaborative Cohort Study (17 CRCs and 17 controls) to reveal how a certain number of patients developed CRC within 2 years after participation. In the discovery phase, miRNA expression measurements were conducted using a 3D-Gene Human miRNA Oligo Chip for 2,555 miRNAs, and RT-qPCR analyses were performed to validate the replicability. In the first validation set with eight CRCs with early clinical stage and eight age- and gender-matched controls, miR-26a-5p and miR-223-3p demonstrated the highest diagnostic accuracy of area under the curve (AUC)=1.000 (sensitivity and specificity 100%). In an examination of the predictability of CRC incidence using pre-clinical cohort samples, miR-26a-5p demonstrated good predictability of advanced CRC incidence with an AUC of 0.840. Overall, the present study revealed serum miR-26a-5p as a potential early detection marker for CRC.
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http://dx.doi.org/10.3892/ol.2022.13207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805182PMC
March 2022

Associations of breastfeeding history with metabolic syndrome and cardiovascular risk factors in community-dwelling parous women: The Japan Multi-Institutional Collaborative Cohort Study.

PLoS One 2022 19;17(1):e0262252. Epub 2022 Jan 19.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Objective: The aim of the present study was to investigate the associations between breastfeeding and the prevalence of metabolic syndrome in community-dwelling parous women and to clarify whether the associations depend on age.

Methods: The present cross-sectional study included 11,118 women, aged 35-69 years. Participants' longest breastfeeding duration for one child and their number of breastfed children were assessed using a self-administered questionnaire, and their total breastfeeding duration was approximated as a product of the number of breastfed children and the longest breastfeeding duration. The longest and the total breastfeeding durations were categorized into none and tertiles above 0 months. Metabolic syndrome and cardiovascular risk factors (obesity, hypertension, dyslipidemia, and hyperglycemia) were defined as primary and secondary outcomes, respectively. Associations between breastfeeding history and metabolic syndrome or each cardiovascular risk factor were assessed using multivariable unconditional logistic regression analysis.

Results: Among a total of 11,118 women, 10,432 (93.8%) had ever breastfed, and 1,236 (11.1%) had metabolic syndrome. In participants aged <55 years, an inverse dose-response relationship was found between the number of breastfed children and the prevalence of metabolic syndrome; multivariable-adjusted odds ratios for 1, 2, 3, and ≥4 breastfed children were 0.60 (95% confidence interval [CI]: 0.31 to 1.17), 0.50 (95% CI: 0.29 to 0.87), 0.44 (95% CI: 0.24 to 0.84), and 0.35 (95% CI: 0.14 to 0.89), respectively. The longest and total breastfeeding durations of longer than 0 months were also associated with lower odds of metabolic syndrome relative to no breastfeeding history in participants aged <55 years. In contrast, all measures of breastfeeding history were not significantly associated with metabolic syndrome and cardiovascular risk factors in participants aged ≥55 years old.

Conclusions: Breastfeeding history may be related to lower prevalence of metabolic syndrome in middle-aged parous women.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262252PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8769371PMC
February 2022

Plasma angiopoietin-like protein 2 levels and mortality risk among younger-old Japanese people: a population-based case-cohort study.

J Gerontol A Biol Sci Med Sci 2022 Jan 17. Epub 2022 Jan 17.

Department of Public Health, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Aging is important medical and social problem. Excessive angiopoietin-like protein (ANGPTL)-2 signaling causes chronic tissue inflammation, promoting development and progression of aging-related diseases. Moreover, circulating ANGPTL2 levels reportedly predict risk of some aging-related diseases and subsequent death. However, there are as yet no reports of whether circulating ANGPTL2 levels predict vital prognosis in younger-old, community-dwelling populations. This study investigated associations between plasma ANGPTL2 levels and all-cause and specific-cause mortality in this population. The case-cohort study was abstracted from an on-going, age-specific prospective cohort study: the New Integrated Suburban Seniority Investigation Project. This project enrolled 3073 participants aged 64 years at the beginning of the investigation from 1996 through 2005. A sub-cohort of 714 randomly sampled participants plus 387 cases representing deceased participants followed through 2015 underwent survival analysis. Plasma ANGPTL2 concentrations were positively associated with >80% and 100% higher risk of all-cause mortality and cancer mortality, respectively, after adjustment for gender, smoking, alcohol consumption, walking time, sleep duration, caloric intake, medical status, disease history, BMI, and triglyceride, creatinine, uric acid, and high sensitivity C-reactive protein levels. More robust association between ANGPTL2 levels and all-cause and cancer mortality was seen in subjects with either frailties or with lifestyles of heavier drinking or current smoking. Elevated plasma ANGPTL2 levels are associated with high all-cause and cancer mortality in a community-dwelling sample of younger-old adults. These findings expand our knowledge of human aging and associated diseases.
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http://dx.doi.org/10.1093/gerona/glac017DOI Listing
January 2022

The association of reproductive history with hypertension and obesity according to menopausal status: the J-MICC Study.

Hypertens Res 2022 Apr 14;45(4):708-714. Epub 2022 Jan 14.

Faculty of Nursing Science, Tsuruga Nursing University, Tsuruga, Japan.

Previous studies have reported that the number of pregnancies and childbirths affected the risk of cardiovascular diseases (CVDs). However, the influence of reproductive history on hypertension and obesity, which are important risk factors for CVDs, is still unclear. Moreover, this association may vary depending on menopausal status. We evaluated the association of reproductive history with hypertension and obesity using a large cross-sectional dataset from the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). At the baseline survey, physical data, blood samples, and self-reported health questionnaires were collected. Participants with insufficient data were excluded, and 24,558 women from eight study regions were included in this study. Logistic regression analysis was conducted to evaluate the association of reproductive history with hypertension and obesity using multivariable-adjusted odds ratios. In premenopausal women, childbirth showed a generally protective effect on hypertension but not on obesity. In postmenopausal women, childbirth was positively associated with obesity and hypertension but not with hypertension after adjusting for BMI. In conclusion, reproductive history was associated with hypertension and obesity in a large Japanese population, and this association differed between premenopausal and postmenopausal women.
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http://dx.doi.org/10.1038/s41440-021-00820-0DOI Listing
April 2022

Association of perceived stress and coping strategies with the renal function in middle-aged and older Japanese men and women.

Sci Rep 2022 01 7;12(1):291. Epub 2022 Jan 7.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Elucidating the risk factors for chronic kidney disease is important for preventing end-stage renal disease and reducing mortality. However, little is known about the roles of psychosocial stress and stress coping behaviors in deterioration of the renal function, as measured by the estimated glomerular filtration rate (eGFR). This cross-sectional study of middle-aged and older Japanese men (n = 31,703) and women (n = 38,939) investigated whether perceived stress and coping strategies (emotional expression, emotional support seeking, positive reappraisal, problem solving, and disengagement) were related to the eGFR, with mutual interactions. In multiple linear regression analyses adjusted for age, area, lifestyle factors, and psychosocial variables, we found a significant inverse association between perceived stress and the eGFR in men (P = 0.02), but not women. This male-specific inverse association was slightly attenuated after adjustment for the history of hypertension and diabetes and was more evident in lower levels of emotional expression (P = 0.003). Unexpectedly, problem solving in men (P < 0.001) and positive reappraisal in women (P = 0.002) also showed an inverse association with the eGFR. Perceived stress may affect the eGFR, partly through the development of hypertension and diabetes. The unexpected findings regarding coping strategies require the clarification of the underlying mechanisms, including the hormonal and immunological aspects.
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http://dx.doi.org/10.1038/s41598-021-04324-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742036PMC
January 2022

Effect of the interaction between physical activity and estimated macronutrient intake on HbA1c: population-based cross-sectional and longitudinal studies.

BMJ Open Diabetes Res Care 2022 01;10(1)

Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Introduction: Healthy diet and physical activity (PA) are essential for preventing type 2 diabetes, particularly, a combination of diet and PA. However, reports on interaction between PA and diet, especially from large epidemiological studies, are limited. We investigated the effect of interaction between PA and macronutrient intake on hemoglobin A1c (HbA1c) levels in the general population.

Research Design And Methods: We conducted a cross-sectional study of 55 469 men and women without diabetes who participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. A self-administered questionnaire ascertained PA and macronutrient intake (carbohydrate, fat, and protein). Multiple linear regression analyses were performed to adjust for confounding variables and examine the interactions. In addition, we conducted a longitudinal study during a 5-year period within a subcohort (n=6881) with accelerometer-assessed PA data.

Results: Overall, PA had a weak inverse association (β=-0.00033, p=0.049) and carbohydrate intake had a strong positive association (β=0.00393, p<0.001) with HbA1c. We observed a tendency of interactions between PA and carbohydrate or fat intake, but not protein intake, on HbA1c levels after adjusting for age, sex, study area, total energy intake, alcohol consumption, smoking, and medication for hypertension or hypercholesterolemia (P=0.054, 0.006, and 0.156, respectively). The inverse associations between PA and HbA1c level were more evident in participants with high-carbohydrate (or low-fat) intake than in participants with low-carbohydrate (or high-fat) intake. Although further adjustment for body mass index slightly attenuated the above interactions (P=0.098 for carbohydrate and 0.068 for fat), the associations between PA and HbA1c level in stratified analyses remained unchanged. Similar associations and interactions were reproduced in the longitudinal study.

Conclusions: The present results suggest that the effect of PA on HbA1c levels is modified by intake of macronutrient composition.
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http://dx.doi.org/10.1136/bmjdrc-2021-002479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724736PMC
January 2022

Association of skipping breakfast and short sleep duration with the prevalence of metabolic syndrome in the general Japanese population: Baseline data from the Japan Multi-Institutional Collaborative cohort study.

Prev Med Rep 2021 Dec 25;24:101613. Epub 2021 Oct 25.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

The purpose of the study was to investigate sex-specific associations of skipping breakfast and short sleep duration with metabolic syndrome (MetS) and their interaction. We analyzed baseline data of 14,907 men and 14,873 women aged 35-69 years, who participated in the Japan Multi-Institutional Collaborative Cohort Study from 2005. MetS was diagnosed using a modification of the National Cholesterol Education Program Adult Treatment Panel III revised definition (NCEP-R 2005), using body mass index instead of waist circumference. Breakfast consumption was classified into two categories: ≥6 days/week (consumers) or <6 days/week (skippers). Sleep duration was classified into three categories: <6h, 6 to <8 h, and ≥8 h/day. Multivariate logistic regression analysis was performed to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) and examine the presence of interaction. In men, skipping breakfast and short sleep duration were independently associated with an increased prevalence of MetS (OR 1.26, 95%CI 1.12-1.42 and OR 1.28, 95%CI 1.12-1.45, respectively), obesity, and components of MetS. However, no significant interaction was observed between skipping breakfast and short sleep duration. In women, skipping breakfast and short sleep duration were associated with an increased prevalence of obesity, but not with MetS. These findings indicate that breakfast consumption and moderate sleep duration may be associated with a lower risk of MetS, particularly in men.
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http://dx.doi.org/10.1016/j.pmedr.2021.101613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8683995PMC
December 2021

Secondhand Smoke Exposure During Childhood and Cancer Mortality in Adulthood Among Never Smokers: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk.

Am J Epidemiol 2022 Mar;191(5):834-842

We examined whether secondhand smoke exposure during childhood was associated with cancer mortality in adulthood among never smokers. In the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, we analyzed data from 45,722 Japanese lifetime nonsmokers aged 40-79 years with no history of cancer at baseline (1988-1990) who had completed a lifestyle questionnaire, including information on the number of family members who had smoked at home during their childhood (0, 1, 2, or ≥3 family members). A Cox proportional hazards model and competing-risks regression were used to calculate multivariable hazard ratios and subdistribution hazard ratios with 95% confidence intervals for overall and site-specific cancer mortality according to the number of family members who smoked during the participant's childhood, after adjusting for potentially confounding factors. During a median follow-up period of 19.2 years, a total of 2,356 cancer deaths were documented. Secondhand smoke exposure was positively associated with the risk of mortality from pancreatic cancer in adulthood; the multivariable hazard ratio for having 3 or more family members who smoked (as compared with none) was 2.32 (95% confidence interval: 1.14, 4.72). Associations were not evident for total cancer risk or risk of other types of smoking-related cancer. In this study, secondhand smoke exposure during childhood was associated with an increased risk of pancreatic cancer mortality in adulthood.
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http://dx.doi.org/10.1093/aje/kwab284DOI Listing
March 2022

Associations of Dietary Salt and Its Sources with Hemoglobin A1c in Patients with Type 2 Diabetes Not Taking Anti-Diabetic Medications: Analysis Based on 6-Month Intervention with a Moderate Low-Carbohydrate Diet.

Diabetes Metab Syndr Obes 2021 19;14:4569-4578. Epub 2021 Nov 19.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya City, Aichi, Japan.

Objective: Based on biological studies, the hyperglycemic effect mediated by sodium-glucose co-transporter 1 in the intestine is stronger for foods containing more sodium chloride. Observational studies have demonstrated that type 2 diabetes (T2DM) incidence increases as salt intake increases. We aimed to elucidate associations of total salt and its sources with hemoglobin A1c (HbA1c) in patients with T2DM.

Methods: We conducted an observational study using data from a 6-month moderate low-carbohydrate dietary intervention in 245 outpatients with T2DM (138 men) without antidiabetic medication. Intakes of total salt and its sources, carbohydrate and total energy were assessed at baseline and 6 months based on 3-day dietary records. Multiple regression analyses were performed to examine associations of Δtotal salt or its sources with ΔHbA1c.

Results: Salt intake significantly decreased in men (change: -0.92 ± 3.53 g/day) but not in women (0.11 ± 2.28). HbA1c (men: -1.5 ± 1.6%; women: -0.9 ± 1.3%), carbohydrate (men: -115 ± 104 g/day; women: -64 ± 71) and total energy (men: -439 ± 660 kcal/day; women: -192 ± 438) significantly decreased in both sexes. Multiple regression analysis revealed that reducing intakes of total salt and salt from salty snacks, meat processed foods, Chinese noodles with soup and table salt by 1.0 g was associated with decreases in HbA1c of 0.11% 1.18% 0.47% 0.38% and 0.26%, respectively, in men, while reducing salt from miso by 1.0 g was associated with a decrease in HbA1c of 0.30% in women. The associations were dependent on Δcarbohydrate or Δtotal energy in men, while the association of Δsalt from miso in women was independent of them.

Conclusion: Reducing total salt and its sources had differential associations with HbA1c. Individual associations depended on Δcarbohydrate or Δtotal energy in men, while that of salt from miso in women was independent of them.
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http://dx.doi.org/10.2147/DMSO.S337032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610379PMC
November 2021

A genome-wide association study on meat consumption in a Japanese population: the Japan Multi-Institutional Collaborative Cohort study.

J Nutr Sci 2021 11;10:e61. Epub 2021 Oct 11.

Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.

Recent genome-wide association studies (GWAS) on the dietary habits of the Japanese population have shown that an effect rs671 allele was inversely associated with fish consumption, whereas it was directly associated with coffee consumption. Although meat is a major source of protein and fat in the diet, whether genetic factors that influence meat-eating habits in healthy populations are unknown. This study aimed to conduct a GWAS to find genetic variations that affect meat consumption in a Japanese population. We analysed GWAS data using 14 076 participants from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. We used a semi-quantitative food frequency questionnaire to estimate food intake that was validated previously. Association of the imputed variants with total meat consumption per 1000 kcal energy was performed by linear regression analysis with adjustments for age, sex, and principal component analysis components 1-10. We found that no genetic variant, including rs671, was associated with meat consumption. The previously reported single nucleotide polymorphisms that were associated with meat consumption in samples of European ancestry could not be replicated in our J-MICC data. In conclusion, significant genetic factors that affect meat consumption were not observed in a Japanese population.
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http://dx.doi.org/10.1017/jns.2021.49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8532070PMC
March 2022

Alcohol intake and stomach cancer risk in Japan: A pooled analysis of six cohort studies.

Cancer Sci 2022 Jan 28;113(1):261-276. Epub 2021 Nov 28.

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

The association between alcohol intake and stomach cancer risk remains controversial. We undertook a pooled analysis of data from six large-scale Japanese cohort studies with 256 478 participants on this topic. Alcohol intake as ethanol was estimated using a validated questionnaire. The participants were followed for incidence of stomach cancer. We calculated study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for stomach cancer according to alcohol intake using a Cox regression model. Summary HRs were estimated by pooling the study-specific HRs using a random-effects model. During 4 265 551 person-years of follow-up, 8586 stomach cancer cases were identified. In men, the multivariate-adjusted HRs (95% CIs) of stomach cancer were 1.00 (0.87-1.15) for occasional drinkers, and 1.00 (0.91-1.11) for <23 g/d, 1.09 (1.01-1.18) for 23 to <46 g/d, 1.18 (1.09-1.29) for 46 to <69 g/d, 1.21 (1.05-1.39) for 69 to <92 g/d, and 1.29 (1.11-1.51) for ≥92 g/d ethanol in regular drinkers compared with nondrinkers. In women, the multivariate-adjusted HRs were 0.93 (0.80-1.08) for occasional drinkers, and 0.85 (0.74-0.99) for <23 g/d, and 1.22 (0.98-1.53) for ≥23 g/d in regular drinkers compared with nondrinkers. The HRs for proximal and distal cancer in drinkers vs nondrinkers were 1.69 (1.15-2.47) and 1.24 (0.99-1.55) for ≥92 g/d in men, and 1.60 (0.76-3.37) and 1.18 (0.88-1.57) for ≥23 g/d in women, respectively. Alcohol intake increased stomach cancer risk in men, and heavy drinkers showed a greater point estimate of risk for proximal cancer than for distal cancer.
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http://dx.doi.org/10.1111/cas.15172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748227PMC
January 2022

Moderate-to-vigorous physical activity and sedentary behavior are independently associated with renal function: a cross-sectional study.

J Epidemiol 2021 Oct 16. Epub 2021 Oct 16.

Department of Preventive Medicine, Tokushima University Graduate School of Biomedical Sciences.

Background: Little is known about whether insufficient moderate-to-vigorous physical activity (MVPA) and longer sedentary behavior (SB) are independently associated with estimated glomerular filtration rate (eGFR) and CKD, whether they interact with known risk factors for CKD, and the effect of replacing sedentary time with an equivalent duration of physical activity on kidney function.

Methods: We examined the cross-sectional association of MVPA and SB with eGFR and CKD in 66,603 Japanese cohort study in 14 areas from 2004 to 2013. MVPA and SB were estimated using a self-reported questionnaire, and CKD was defined as eGFR<60 mL/min/1.73 m. Multiple linear regression analyses, logistic regression analyses, and an isotemporal substitution model were applied.

Results: After adjusting for potential confounders, higher MVPA and longer SB were independently associated with higher eGFR (P<0.0001) and lower eGFR (P<0.0001), and a lower odds ratio (OR) of CKD (adjusted OR of MVPA≥20 MET·h/day: 0.76 [95%CI: 0.68-0.85] compared to MVPA<5 MET·h/day) and a higher OR of CKD (adjusted OR of SB≥16 h/day: 1.81 [95%CI: 1.52-2.15] compared to SB<7 h/day), respectively. The negative association between MVPA and CKD was stronger in men, and significant interactions between sex and MVPA were detected. Replacing 1 hour of SB with 1 hour of physical activity was associated with about 3 to 4% lower OR of CKD.

Conclusions: These findings indicate that replacing SB with physical activity may benefit kidney function, especially in men, adding to the possible evidence on CKD prevention.
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http://dx.doi.org/10.2188/jea.JE20210155DOI Listing
October 2021

Dairy products and the risk of developing prostate cancer: A large-scale cohort study (JACC Study) in Japan.

Cancer Med 2021 10 4;10(20):7298-7307. Epub 2021 Oct 4.

Department of Public Health, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Dairy products have been indicated as a risk factor for prostate cancer. However, only a few epidemiological studies have reported dairy products as being a risk factor for prostate cancer in Japan, reporting contradictory results. We therefore investigated the association between the intake of dairy products and the occurrence of prostate cancer through a large-scale cohort study. The Japan Collaborative Cohort study analyzed approximately 110,000 residents from various Japanese districts who participated in our questionnaire survey during 1988-1990. The subjects of the present study were 26,464 men (age range: 40-79 years) from 24 districts wherein cancer incidence was reported. Their clinical course was followed up until 2009. Hazard ratios (HRs) were calculated using Cox's proportional hazards model, adjusted for age, survey area, family history of prostate cancer, body mass index, and total energy intake. For diet, we calculated the HRs associated with intermediate and high consumption of dairy products and compared them with those associated with low consumption. There were 412 cases of prostate cancer in the survey population. As dairy products, milk, yogurt, cheese, and butter were evaluated. Among them, milk consumption was associated with a significant risk (HR = 1.37, p = 0.009) and a dose-dependent response (p for trend = 0.009) adjusted for age and family history of prostate cancer, stratified by area. Milk and yogurt consumption showed a significantly positive risk and a dose-response relationship adjusted for age, family history of prostate cancer, body mass index, and total energy intake, stratified by area. In summary, a high intake of dairy products such as milk increased the risk of developing prostate cancer in Japanese men.
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http://dx.doi.org/10.1002/cam4.4233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525158PMC
October 2021

Sex-specific Relationship between Stress Coping Strategies and All-Cause Mortality: Japan Multi-Institutional Collaborative Cohort Study.

J Epidemiol 2021 Sep 25. Epub 2021 Sep 25.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine.

Background: Stress coping strategies are related to health outcomes. However, there is no clear evidence for sex differences between stress-coping strategies and mortality. We investigated the relationship between all-cause mortality and stress-coping strategies, focusing on sex differences among Japanese adults.

Methods: A total of 79,580 individuals aged 35-69 years participated in the Japan Multi-Institutional Collaborative Cohort Study between 2004 and 2014 and were followed up for mortality. The frequency of use of the five coping strategies was assessed using a questionnaire. Sex-specific, multivariable-adjusted hazard ratios (HRs) for using each coping strategy "sometimes," and "often/very often" (versus "very few" use) were computed for all-cause mortality. Furthermore, relationships were analyzed in specific follow-up periods when the proportion assumption was violated.

Results: During the follow-up (median: 8.5 years), 1,861 mortalities were recorded. In women, three coping strategies were related to lower total mortality. The HRs (95% confidence intervals) for "sometimes" were 0.81 (0.67-0.97) for emotional expression, 0.79 (0.66-0.95) for emotional support-seeking, and 0.80 (0.66-0.98) for disengagement. Men who "sometimes" used emotional expression and sometimes or often used problem-solving and positive reappraisal had a 15-41% lower HRs for all-cause mortality. However, those relationships were dependent on the follow-up period. There was evidence that sex modified the relationships between emotional support-seeking and all-cause mortality (p for interaction = 0.03).

Conclusions: In a large Japanese population, selected coping strategies were associated with all-cause mortality. The relationship of emotional support-seeking was different between men and women.
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http://dx.doi.org/10.2188/jea.JE20210220DOI Listing
September 2021

Insulin-Like Growth Factor 2 and Incidence of Liver Cancer in a Nested Case-Control Study.

Cancer Epidemiol Biomarkers Prev 2021 11 8;30(11):2130-2135. Epub 2021 Sep 8.

Department of Preventive Medicine, Nagoya University, Graduate School of Medicine, Nagoya, Japan.

Background: Insulin-like growth factor (IGF)2 is a potent mitogen. To elucidate the relationship between IGF2 and risk of tumorigenesis, we analyzed associations between serum levels of IGF2 and incidence of liver cancer in a prospective case-control study nested in the Japan Collaborative Cohort study.

Methods: A baseline survey was conducted from 1988 using blood samples from 39,242 subjects. Those who had been diagnosed with liver cancer by 1997 were regarded as cases. For each case, we randomly selected two or three controls matched for sex, age, and residential area. Conditional logistic regression was used to estimate ORs for cancer incidence associated with IGF2.

Results: This analysis included 86 cases and 294 controls. Low IGF2 was associated with risk of future liver cancer ( <0.001). After controlling for alcohol intake, body mass index, smoking, hepatitis viral infection, IGF1, and IGF-binding protein-3, participants with low IGF2 displayed a higher risk of liver cancer ( < 0.001). Individuals in quintiles 2 to 5 showed lower risk compared with quintile 1 (OR range, 0.05-0.16). In both sexes and in both nonelderly and elderly groups, subjects in the lowest quintiles showed higher risks of liver cancer. Limiting subjects to those followed for 3 years, low IGF2 was associated with cancer risk ( < 0.001).

Conclusions: Our findings suggest that low serum IGF2 level, especially below 460 ng/mL, is related to future risk of liver cancer.

Impact: Our findings highlight this important biomarker for further analysis in large prospective cohorts and pooled investigation with other cohorts.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0481DOI Listing
November 2021

A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants of among 30,685 Japanese Individuals.

Biomedicines 2021 Aug 13;9(8). Epub 2021 Aug 13.

Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan.

Background: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FE). Further studies on FE in hypouricemic individuals are needed for a more accurate diagnosis of RHUC.

Methods: In 30,685 Japanese health-examination participants, we genotyped the two most common nonfunctional variants of (NFV-), W258X (rs121907892) and R90H (rs121907896), in 1040 hypouricemic individuals (SUA ≤ 3.0 mg/dL) and 2240 individuals with FE data. The effects of NFV- on FE and SUA were also investigated using linear and multiple regression analyses.

Results: Frequency of hypouricemic individuals (SUA ≤ 3.0 mg/dL) was 0.97% (male) and 6.94% (female) among 30,685 participants. High frequencies of those having at least one allele of NFV- were observed in 1040 hypouricemic individuals. Furthermore, NFV- significantly increased FE and decreased SUA, enabling FE and SUA levels to be estimated. Conversely, FE and SUA data of hypouricemic individuals are revealed to be useful to predict the number of NFV-.

Conclusions: Our findings reveal that specific patterns of FE and SUA data assist with predicting the number of nonfunctional variants of causative genes for RHUC, and can also be useful for practical diagnosis of RHUC even before genetic tests.
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http://dx.doi.org/10.3390/biomedicines9081012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393673PMC
August 2021

Population-Based Impact of Smoking, Drinking, and Genetic Factors on HDL-Cholesterol Levels in J-MICC Study Participants.

J Epidemiol 2021 Aug 21. Epub 2021 Aug 21.

Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN.

Background: Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C.

Methods: Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10) were selected from the GWAS catalog, and seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF).

Results: We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively.

Conclusions: The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking.
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http://dx.doi.org/10.2188/jea.JE20210142DOI Listing
August 2021

Tooth brushing, tooth loss, and risk of upper aerodigestive tract cancer: a cohort study of Japanese dentisits.

Nagoya J Med Sci 2021 May;83(2):331-341

Kyoto University Health Service, Kyoto, Japan.

Previous studies have focused on the association between poor oral health and upper aerodigestive tract (UADT) cancer. However, whether toothbrushing and tooth loss are associated with UADT cancer risk is still unclear. Therefore, we investigated the association between toothbrushing or tooth loss and UADT cancer in the Longitudinal Evaluation of Multi-phasic, Odontological, and Nutritional Associations in Dentists (LEMONADE) cohort study. From 2001 to 2006, we recruited 20,445 dentists (mean age ± standard deviation, 51.8 ± 12.0 years; 1,607 women [7.9%]) and followed for incidence or mortality of UADT cancer through March 2014. Information on lifestyle and oral health was collected by the baseline questionnaire. The Cox proportional hazards model was used to estimate hazard ratios (HRs) for UADT cancer and corresponding 95% confidence intervals (CI) for brushing frequency and tooth loss with adjustment for covariates. During the mean follow-up of 9.5 years, we confirmed 62 incident or fatal cases of UADT cancer. Infrequent toothbrushing (< 2 times/day) was significantly associated with increased risk of UADT cancer (multivariate HR = 2.13, 95% CI: 1.04-4.37). On the contrary, tooth loss was not significantly correlated with UADT cancer risk; multivariate HR was 1.03 (95% CI: 0.41-2.61) for loss of 15-27 teeth and 1.37 (0.50-3.75) for that of 28 teeth compared to tooth loss of 0-14 teeth. In conclusion, Infrequent toothbrushing was significantly associated with the risk of UADT cancer.
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http://dx.doi.org/10.18999/nagjms.83.2.331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236682PMC
May 2021

Association between frequency of snacking and all-cause mortality among community-dwelling young-old adults: An age-specific prospective cohort study.

Geriatr Gerontol Int 2021 Aug 25;21(8):697-704. Epub 2021 Jun 25.

Department of Public Health, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan.

Aim: We aimed to clarify whether snacking habits decrease the risk of all-cause mortality in an older Japanese population.

Methods: The study participants were 64- or 65-year-old community-dwelling residents recruited each survey year from 1996 through 2005. Data on the frequency of snacking and other lifestyle factors were obtained during the baseline survey using self-administered questionnaires, and the participants were followed up annually until the end of 2017. In total, 2943 participants (1484 men and 1459 women) were eligible. All-cause mortality was compared among participants grouped by frequency of snacking (no snacking, one to four times/week, or every day).

Results: The number of deaths recorded over the study period of 43 204 person-years was 357 (24.1%) for men and 173 (11.9%) for women. The mean ± standard deviations for the follow-up period were 14.2 ± 4.9 years in men and 15.2 ± 4.5 years in women. Cox proportional hazard regression analyses showed that after adjusting for potential confounding factors, the hazard ratios for women were 0.64 (95% confidence interval [CI], 0.43-0.94) in the group that had a habit of snacking one to four times/week, and 0.93 (95% CI 0.63-1.36) in the group that had a habit of snacking every day compared with those in the no snacking group. These associations were not observed among men.

Conclusions: A moderate frequency of snacking slightly decreases the risk of all-cause mortality among women. Our findings might be useful for improving the nutrition statuses in older female adults. Geriatr Gerontol Int 2021; 21: 697-704.
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http://dx.doi.org/10.1111/ggi.14209DOI Listing
August 2021

Comparison of frailty associated factors between older adult patients with rheumatoid arthritis and community dwellers.

Arch Gerontol Geriatr 2021 Sep-Oct;96:104455. Epub 2021 Jun 2.

Department of Frailty, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Obu, Japan; Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Purpose: To determine whether frailty associated factors differ between community dwellers and older adult patients with rheumatoid arthritis (RA).

Methods: We used the cross-sectional data for patients with RA from the RA epidemiological quality-of-life study (n = 210, mean age 71.8 ± 3.7 years) and community dwellers from the Japan Gerontological Evaluation Study (n = 53,255, mean age 71.7 ± 4.0 years). Frailty status was assessed using the Kihon Checklist (KCL), and the primary outcome was frailty (KCL score ≥8 points). Information on predictor variables, including age, sex, marital status, educational level, body mass index (BMI), drinking and smoking status and social participation were obtained from a standardized questionnaire. We employed Poisson regression to calculate the prevalence ratio (PR) of frailty according to its predictors.

Results: We found frailty in 37.6% of the patients with RA and 15.7% of the community dwellers. In the multivariate models, BMI and social participation were independently associated with frailty in patients with RA (BMI <18.5: PR, 1.62; 95% confidence interval [CI] 1.09-2.41. BMI ≥25.0: PR, 1.81; 95% CI 1.20-2.71. Active social participation: PR, 0.61; 95% CI 0.42-0.87) and community dwellers (BMI <18.5: PR, 1.77; 95% CI 1.67-1.88. BMI ≥25.0: PR, 1.27; 95% CI 1.22-1.33. Active social participation: PR, 0.46; 95% CI 0.44-0.48). All other predictors were significantly associated with frailty in the community dwellers.

Conclusion: Maintaining appropriate body weight and participating in social activities are important for preventing frailty in patients with RA as well as community dwellers.
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http://dx.doi.org/10.1016/j.archger.2021.104455DOI Listing
September 2021

Effect of Underlying Cardiometabolic Diseases on the Association Between Sedentary Time and All-Cause Mortality in a Large Japanese Population: A Cohort Analysis Based on the J-MICC Study.

J Am Heart Assoc 2021 07 14;10(13):e018293. Epub 2021 Jun 14.

Department of Preventive Medicine Nagoya University Graduate School of Medicine Aichi Japan.

Background This study aimed to determine the association between sedentary time and mortality with regard to leisure-time physical activity with or without cardiometabolic diseases such as hypertension, dyslipidemia, and diabetes mellitus. Methods and Results Using data from the J-MICC (Japan Multi-Institutional Collaborative Cohort) Study, 64 456 participants (29 022 men, 35 434 women) were analyzed. Hazard ratios (HRs) and 95% CIs were used to characterize the relative risk of all-cause mortality to evaluate its association with sedentary time (categorical variables: <5, 5 to <7, 7 to <9, ≥9 h/d and 2-hour increments in exposure) according to the self-reported hypertension, dyslipidemia, and diabetes mellitus using a Cox proportional hazards model. A total of 2257 participants died during 7.7 years of follow-up. The corresponding HRs for each 2-hour increment in sedentary time among participants with all factors, no factors, hypertension, dyslipidemia, and diabetes mellitus were 1.153 (95% CI, 1.114-1.194), 1.125 (95% CI, 1.074-1.179), 1.202 (95% CI, 1.129-1.279), 1.176 (95% CI, 1.087-1.273), and 1.272 (95% CI, 1.159-1.396), respectively. Furthermore, when analyzed according to the combined different factors (hypertension, dyslipidemia, and diabetes mellitus), HRs increased with each additional factor, and participants reporting all 3 conditions had the highest HR of 1.417 (95% CI, 1.162-1.728) independently of leisure-time metabolic equivalents. Conclusions The association between sedentary time and increased mortality is stronger among patients with hypertension, dyslipidemia, and diabetes mellitus regardless of leisure-time physical activity in a large Japanese population.
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http://dx.doi.org/10.1161/JAHA.120.018293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403304PMC
July 2021

Erratum to: Response to Dr Shikata's letter: 'Secondhand smoke exposure and risk of lung cancer in Japan: a systematic review and meta-analysis of epidemiologic studies'.

Jpn J Clin Oncol 2021 May;51(6):1021

Division of Cancer Statistics Integration, Center for Cancer Control and Information Services, National Cancer Center, Tokyo, Japan.

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http://dx.doi.org/10.1093/jjco/hyab053DOI Listing
May 2021

Prediction of 11-year incidence of psychophysically dependent status or death among community-dwelling younger elderlies: from an age-specified community-based cohort study (the NISSIN project).

Environ Health Prev Med 2021 Apr 10;26(1):45. Epub 2021 Apr 10.

Department of Public Health, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan.

Background: Predicting adverse health events and implementing preventative measures are a necessary challenge. It is important for healthcare planners and policymakers to allocate the limited resource to high-risk persons. Prediction is also important for older individuals, their family members, and clinicians to prepare mentally and financially. The aim of this study is to develop a prediction model for within 11-year dependent status requiring long-term nursing care or death in older adults for each sex.

Methods: We carried out age-specified cohort study of community dwellers in Nisshin City, Japan. The older adults aged 64 years who underwent medical check-up between 1996 and 2000 were included in the study. The primary outcome was the incidence of the psychophysically dependent status or death or by the end of the year of age 75 years. Univariable logistic regression analyses were performed to assess the associations between candidate predictors and the outcome. Using the variables with p-values less than 0.1, multivariable logistic regression analyses were then performed with backward stepwise elimination to determine the final predictors for the model.

Results: Of the 1525 female participants at baseline, 105 had an incidence of the study outcome. The final prediction model consisted of 15 variables, and the c-statistics for predicting the outcome was 0.763 (95% confidence interval [CI] 0.714-0.813). Of the 1548 male participants at baseline, 211 had incidence of the study outcome. The final prediction model consisted of 16 variables, and the c-statistics for predicting the outcome was 0.735 (95% CI 0.699-0.771).

Conclusions: We developed a prediction model for older adults to forecast 11-year incidence of dependent status requiring nursing care or death in each sex. The predictability was fair, but we could not evaluate the external validity of this model. It could be of some help for healthcare planners, policy makers, clinicians, older individuals, and their family members to weigh the priority of support.
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http://dx.doi.org/10.1186/s12199-021-00968-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035719PMC
April 2021
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