The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies ...the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi‐Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3‐year follow‐up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60‐74 ml/min/1.73 m2, the adjusted hazard ratios (HRs) (95% confidence intervals CIs) for eGFRs of ≥90, 75‐89, 45‐59, 30‐44 and 10‐29 ml/min/1.73 m2 were 1.18 (1.07‐1.29), 1.09 (1.01‐1.17), 0.93 (0.83‐1.04), 1.36 (1.00‐1.84) and 1.12 (0.55‐2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75‐89 ml/min/1.73 m2 were 1.58 (1.29‐1.94) and 1.27 (1.08‐1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m2 revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m2, with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U‐shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.
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Despite suspected associations between chronic kidney disease and cancer, it remains unknown whether kidney function modifies cancer risk. Moreover, the majority of studies examining possible associations have involved Caucasian populations, with limited investigation particularly of Asian groups. The present analysis explored potential links between kidney function and cancer among Japanese patients. Analyses reveal a U‐shaped relationship between estimated glomerular filtration rate (eGFR) and cancer incidence, wherein cancer risk was elevated in association with moderately low and high eGFR. Cancer risk from smoking increased as eGFR decreased, highlighting the importance of avoiding smoking, especially in the context of reduced kidney function.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective: Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) have been shown to accumulate in the human body. The purpose of the present study was to examine the factors associated with ...the blood levels of PFOS and PFOA. Methods: A cross-sectional study was performed on 307 men and 301 women (aged 16-76 years) living in 15 prefectures in Japan. Blood levels of PFOS and PFOA were measured by liquid chromatography-mass spectrometry. Hepatic enzymes (γ-GTP, GOT, and GPT) and ω-3 polyunsaturated fatty acids (DHA and EPA) levels in serum were also measured. Associations between the levels of PFOS and PFOA in blood and the intake frequency of 41 kinds of dishes, foods and beverages and the serum levels of liver enzymes and ω-3 polyunsaturated fatty acids were examined using rank correlations. Results: Frequency of intake of boiled fish in broth, sliced raw fish and coastal fish showed significant positive correlations with PFOS concentrations in blood after adjustments for potential confounders. Serum levels of GOT, GPT, DHA and EPA showed significant positive correlations with PFOS and PFOA in blood. There was also a significant regional difference in the blood levels of PFOS and PFOA, with medians being highest in the Tokai/Hokuriku/Kinki region. Conclusions: These findings suggest that the concentrations of PFOS in blood were mainly associated with fish consumption and that the levels of PFOS and PFOA were associated with the serum levels of liver enzymes in Japanese populations. Further investigations are required to clarify the reason for the regional differences in blood levels of PFOS and PFOA in Japan.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene–environment interactions in lifestyle-related diseases, including cancers, among the ...Japanese. This report describes the study design and baseline profile of the study participants.Methods: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history and collected peripheral blood samples.Results: The baseline survey included 92,610 adults (mean age: 55.2 standard deviation, 9.4 years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65–69 years for men and 60–64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women.Conclusions: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Backgrounds: The fatty liver index (FLI) is a good non-invasive approach for fatty liver disease diagnosis. The objective of this study was to examine the associations of nutrient patterns with ...non-alcoholic fatty liver disease (NAFLD) in a Japanese population.Methods: A total of 1,588 subjects (789 men and 799 women) aged 35–69 years were recruited in the baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima Prefecture. Factor analysis was applied to energy-adjusted intake of 21 nutrients, and nutrient patterns were extracted. Multiple logistic regression analysis was used to analyze the relationships between nutrient patterns and the high FLI category (≥60).Results: Four nutrient patterns were extracted: Factor 1, vitamins, dietary fiber, iron and potassium pattern; Factor 2, fats and fat-soluble vitamins pattern; Factor 3, saturated fat, calcium, vitamin B2 and low carbohydrate pattern; and Factor 4, sodium, protein and vitamin D pattern. After adjustment for sex, age, and other potential confounding variables, higher Factor 1 scores were significantly associated with lower odds ratios of NAFLD (P for trend <0.05). Analysis of each component of FLI showed that there were significant inverse associations between Factor 1 scores and high body mass index and large waist circumference.Conclusion: The present findings suggest that a nutrient pattern rich in vitamins, fiber, iron, and potassium was associated with lower prevalence of NAFLD in a Japanese population. Obesity and abdominal obesity may be intermediate variables for the association between this nutrient pattern and NAFLD.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
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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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background: Although many observational studies have demonstrated significant relationships between obesity and cardiometabolic traits, the causality of these relationships in East Asians remains to ...be elucidated.Methods: We conducted individual-level Mendelian randomization (MR) analyses targeting 14,083 participants in the Japan Multi-Institutional Collaborative Cohort Study and two-sample MR analyses using summary statistics based on genome-wide association study data from 173,430 Japanese. Using 83 body mass index (BMI)-related loci, genetic risk scores (GRS) for BMI were calculated, and the effects of BMI on cardiometabolic traits were examined for individual-level MR analyses using the two-stage least squares estimator method. The β-coefficients and standard errors for the per-allele association of each single-nucleotide polymorphism as well as all outcomes, or odds ratios with 95% confidence intervals were calculated in the two-sample MR analyses.Results: In individual-level MR analyses, the GRS of BMI was not significantly associated with any cardiometabolic traits. In two-sample MR analyses, higher BMI was associated with increased risks of higher blood pressure, triglycerides, and uric acid, as well as lower high-density-lipoprotein cholesterol and eGFR. The associations of BMI with type 2 diabetes in two-sample MR analyses were inconsistent using different methods, including the directions.Conclusion: The results of this study suggest that, even among the Japanese, an East Asian population with low levels of obesity, higher BMI could be causally associated with the development of a variety of cardiometabolic traits. Causality in those associations should be clarified in future studies with larger populations, especially those of BMI with type 2 diabetes.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Background: Nutrients have been proposed to be related to metabolic syndrome (MetS). The aims of this study were to identify dietary patterns that correlated with several nutrients using reduced rank ...regression (RRR) and to examine the association between extracted dietary patterns and prevalence of MetS in a Japanese population. Methods: The study population comprised 1,092 Japanese men and women (35–69 years old) who had participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study in Tokushima Prefecture. Dietary patterns were derived with RRR using 46 food items as predictors and six established nutrients (potassium, calcium, vitamin D, vitamin C, insoluble dietary fiber, and carotene) as response variables. Associations between extracted dietary patterns and MetS were then examined with logistic regression models. Results: Among the six dietary patterns, dietary pattern 1 (DP1) explained the largest proportion (60.1%) of variance in the six nutrients. Therefore, only DP1 was selected for further analysis. DP1 was characterized by high intake frequency of vegetables, fruits, fish and small fish, natto (fermented soybeans), and deep-fried tofu. After adjustment for potential confounders, significant inverse associations were found between DP1 score and MetS (odds ratio OR for each quartile: 1.00, 0.58, 0.60, 0.52; Ptrend = 0.02); DP1 and high blood pressure (Ptrend = 0.0002); and DP1 and high blood glucose (Ptrend = 0.02). Conclusion: A dietary pattern characterized by high intake of vegetables, fruits, fish and small fish, natto, and deep-fried tofu was associated with reduced prevalence of MetS in a Japanese population.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Aims: The association between dietary patterns and serum low density lipoprotein (LDL) cholesterol would be changing in recent dietary habits in Japan. We investigated the relationship between ...dietary patterns and serum LDL cholesterol in a large general population.Methods: From the baseline survey of Japan Multi-Institutional Collaborative Cohort Study between 2005 and 2013, 27,237 participants (13,994 were women) aged 35–69 years were cross-sectionally analyzed. Using a semi-quantitative food frequency questionnaire, five major sex-specific dietary patterns were identified using factor analysis. We assessed serum LDL cholesterol by quintiles of dietary pattern factor score.Results: We identified dietary patterns; “vegetable rich pattern” , “meat and fried food rich pattern” and “high bread and low rice pattern” in women and men; “fish and shellfish rich pattern” and “high confectioneries and low alcohol pattern” in men; “healthy Japanese diet pattern” and “high alcohol and low rice pattern” in women. Serum LDL cholesterol in men was associated with “high bread and low rice pattern” score (Q5 was 4.2 mg/dL higher than Q1, p for trend ＜0.001) and “high confectioneries and low alcohol pattern” scores (Q5 was 9.5 mg/dL higher than Q1, p for trend ＜0.001). In women, serum LDL cholesterol was associated with “high bread and low rice pattern” score (Q5 was 7.1 mg/dL higher than Q1, p for trend ＜0.001).Conclusion: Some recent dietary patterns in Japan were associated with serum LDL cholesterol. Serum LDL cholesterol was associated with high bread and low rice pattern in both sex, and high confectioneries and low alcohol pattern in men.
Background: Inflammation is thought to be a risk factor for kidney disease. However, whether inflammatory status is either a cause or an outcome of chronic kidney disease remains controversial. We ...aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using Mendelian randomization (MR) approaches.Methods: A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IVCRP and IVAsian, based on SNPs previously identified in European and Asian populations. IVCRP and IVAsian explained 3.4% and 3.9% of the variation in hs-CRP, respectively.Results: Using the IVCRP, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 0.000; 95% confidence interval CI, −0.019 to 0.020 and −0.003; 95% CI, −0.019 to 0.014, respectively). For IVAsian, we found similar results using the IVW and the WM methods (estimate, 0.005; 95% CI, −0.020 to 0.010 and −0.004; 95% CI, −0.020 to 0.012, respectively). The MR-Egger method also showed no causal relationships between hs-CRP and eGFR (IVCRP: −0.008; 95% CI, −0.058 to 0.042; IVAsian: 0.001; 95% CI, −0.036 to 0.036).Conclusion: Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
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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