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Background: Obesity is a reported risk factor for various health problems. Genome-wide association studies (GWASs) have identified numerous independent loci associated with body mass index (BMI). However, most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities. Methods: We conducted a cross-sectional study to examine the associations of 282 GWAS-identified single nucleotide polymorphisms with three BMI-related traits, current BMI, BMI at 20 years old (BMI at 20), and change in BMI (BMI change), among 11,586 Japanese individuals enrolled in the Japan Multi-Institutional Collaborative Cohort study. Associations were examined using multivariable linear regression models. Results: We found a significant association (P < 0.05/282 = 1.77 × 10−4) between BMI and 11 polymorphisms in or near FTO, BDNF, TMEM18, HS6ST3, and BORCS7. The trend was similar between current BMI and BMI change, but differed from that of the BMI at 20. Among the significant variants, those on FTO were associated with all BMI traits, whereas those on TMEM18 and HS6SR3 were only associated with BMI at 20. The association of FTO loci with BMI remained, even after additional adjustment for dietary energy intake. Conclusions: Previously reported BMI-associated loci discovered in Europeans were also identified in the Japanese population. Additionally, our results suggest that the effects of each loci on BMI may vary across the life course and that this variation may be caused by the differential effects of individual genes on BMI via different pathways.

Prostate cancer is emerging as a significant global public health burden. The incidence and prevalence of prostate cancer has increased in Japan, as westernized lifestyles become more popular. Recent advances in genetic epidemiology, including genome-wide association studies (GWASs), have identified considerable numbers of human genetic factors associated with diseases. Several GWASs have reported significant loci associated with serum prostate-specific antigen (PSA) levels. One GWAS, which was based on classic GWAS microarray measurements, has been reported for Japanese so far. In the present study, we conducted a GWAS of serum PSA using 1000Genomes imputed GWAS data (n =1,216) from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, to detect candidate novel genetic loci that influence serum PSA levels in Japanese. The association of SNPs/genetic variants with serum PSA as a continuous variable was tested using the linear Wald test. SNP rs10000006 in SGMS2 (sphingomyelin synthase 2) on chromosome 4 had genome-wide significance (P, This is an Open Access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view the details of this license, please visit (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Forest walking or Shinrin-yoku is a health promotion activity in Japan. Although some studies have reported the acute effects of walking a few hours in forested areas in reducing blood pressure level compared to other environments, studies investigating whether successive walking has long-term effects in lowering blood pressure levels or lowering prevalence of hypertension are rare. This study aimed to reconfirm the presence or absence of an association between the frequency of forest walking and prevalence of hypertension in a Japanese population. This J-MICC Daiko Study was conducted targeting residents in Nagoya City. A total of 5,109 participants (1,452 men and 3,657 women; age, mean ± standard deviation: 52.5 ± 10.3 years) were included in the analysis. Age-adjusted blood pressure level by frequency of forest walking was not significant. After adjusting for age and lifestyle, the adjusted odds ratios (aORs) of the most frequent group (n=88, 1.7%; once a week or more group) relative to the less than once a month group (n=4,558, 89.2%) for prevalence of hypertension were not also significant [0.80 (95% CI: 0.40–1.62) for men and 1.48 (95% CI: 0.73–3.00) for women]. This study reconfirmed that either lowering blood pressure level or lowering the prevalence of hypertension is not associated with frequency of forest walking, similar to the results of our previous J-MICC Shizuoka Study. Given that these two studies were cross-sectional studies, cohort studies investigating the causal relationship are required to evaluate the effect of frequent forest walking on the prevention of hypertension., This study was supported by Grant-in-Aid for Scientific Research on Priority Areas of Cancer (No. 17015018), Innovative Areas (No. 221S0001), and JSPS KAKENHI Grant (No. 16H06277 and 18K11065) from the Ministry of Education, Culture, Sports, Science and Technology, Japan and Foundation for Total Health Promotion, Japan.

Purpose The association between metabolic syndrome (MetS) and the risk of death from cancer is still a controversial issue. The purpose of this study was to examine the associations of MetS and metabolically unhealthy obesity (MUHO) with cancer mortality in a Japanese population. Methods We used data from the Japan Multi-Institutional Collaborative Cohort Study. The study population consisted of 28,554 eligible subjects (14,103 men and 14,451 women) aged 35–69 years. MetS was diagnosed based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) and the Japan Society for the Study of Obesity (JASSO), using the body mass index instead of waist circumference. The Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for total cancer mortality in relation to MetS and its components. Additionally, the associations of obesity and the metabolic health status with cancer mortality were examined. Results During an average 6.9-year follow-up, there were 192 deaths from cancer. The presence of MetS was significantly correlated with increased total cancer mortality when the JASSO criteria were used (HR = 1.51, 95% CI 1.04–2.21), but not when the NCEP-ATP III criteria were used (HR = 1.09, 95% CI 0.78–1.53). Metabolic risk factors, elevated fasting blood glucose, and MUHO were positively associated with cancer mortality (P

Aim: Stroke is associated closely with vascular homeostasis, and several complex processes and interacting pathways, which involve various genetic and environmental factors, contribute to the risk of stroke. Although adrenomedullin (ADM) has a number of physiological and vasoprotective functions, there are few studies of the ADM receptor system in humans. The ADM receptor comprises a calcitonin-receptor-like receptor (CLR) and receptor activity-modifying proteins (RAMPs). We analyzed single nucleotide polymorphisms (SNPs) in the RAMP2 and CLR genes to determine their association with stroke in the light of gene-environment interactions. Methods: Using cross-sectional data from the Japan Multi-Institutional Collaborative Cohort Study in the baseline surveys, 14,087 participants from 12 research areas were genotyped. We conducted a hypothesis-based association between stroke prevalence and SNPs in the RAMP2 and CLR genes based on data abstracted from two SNPs in RAMP2 and 369 SNPs in CLR. We selected five SNPs from among the CLR variants (rs77035639, rs3815524, rs75380157, rs574603859, and rs147565266) and one RAMP2 SNP (rs753152), which were associated with stroke, for analysis. Results: Five of the SNPs (rs77035639, rs3815524, rs75380157, rs147565266, and rs753152) showed no significant association with obesity, ischemic heart disease, hypertension, dyslipidemia, and diabetes. In the logistic regression analysis, rs574603859 had a lower odds ratio (0.238; 95% confidence interval, 0.076–0.745, adjusted for age, sex, and research area) and the other SNPs had higher odds ratios for association with stroke. Conclusions: This was the first study to investigate the relationships between ADM receptor genes (RAMP2 and CLR) and stroke in the light of gene-environment interactions in human.

Occupation could affect the distribution of smoking status of workers, and the success of smoking cessation among workers depends partly on worksite conditions. Blue collar workers have been identified as a high-risk group for smoking. The aim of the present study was to examine trends in smoking rates among urban civil servants in Japan according to occupational categories. Subjects were urban civil servants aged 30–59 years. They annually reported smoking status in a questionnaire in a worksite health check-up each year from 2004 to 2011. Urban civil servants reported substantially lower current smoking rates than national smoking rates in Japan (20.2%, 23.8%, and 27.0% for males in their 30s, 40s, and 50s and 2.4%, 6.3%, and 9.5% for females, respectively, in 2011). In analysis by occupational categories, current smoking rates declined among all groups except female white collar workers in their 50s. The current and persistent smoking rates (number of current smokers/[number of ex-smokers and current smokers]) among blue collar workers were higher than those among white collar workers at almost all time points in all age and gender groups. This study found relatively lower current smoking rates among urban civil servants than the national average and higher current and persistent smoking rates in blue collar workers than in white collar workers among them. These results would help to make suitable worksite smoking cessation policies for each occupational category.

The genome-wide association study identified associations between the LRP2 polymorphism rs2544390 and serum uric acid (SUA) levels in a Japanese population. Our previous study on the LRP2 rs2544390 polymorphism identified an interaction between SUA and alcohol consumption. Here, we investigated an interaction with body mass index (BMI) using the same dataset. Subjects were 3,742 health checkup examinees (2,544 males and 1,198 females) aged 35–69 years. Those with the SLC22A12 258WW genotype, SLC2A9 rs11722228 C allele, and ABCG2 126QQ genotype and 141Q allele were selected for analysis to remove the strong influences of these genetic traits. In males, the odds ratio of BMI ≥25.0 relative to BMI

Prostate specific antigen (PSA) testing plays a major role in prostate cancer screening; however, the low positive predictive value of PSA testing leads to many unnecessary biopsies. Genetic background is one of factors that could cause it. That’s why an association between genetic background and PSA levels should be elucidated. This study aimed to investigate whether DPP4 genetic variants are associated with baseline PSA levels. A cross-sectional study was performed on 2,074 Japanese men aged between 35 and 69 in the Shizuoka area from the Japan Multi-institutional Collaborative Cohort (J-MICC) Study. Three DPP4 tagging single nucleotide polymorphisms (SNPs) were selected for genotyping: rs3788979 (A/G), rs7608798 (T/C), and rs2268889 (A/G). Higher mean serum PSA levels were significantly associated with an increase in the number of the rs7608798 C allele (p for trend = 0.02). A stratified analysis by age groups demonstrated that PSA levels had positive significant trends with the numbers of the minor alleles of rs3788979 or rs7608798 in the oldest group (men aged between 60 and 69) (p for trend=0.004 for rs3788979 and p for trend=0.001 for rs7608798). Haplotype analysis showed that the C-A (rs7608798- rs2268889) haplotype was significantly associated with increased PSA levels (p=0.006), compared with the most common haplotype, T-A. In summary, our study suggests that DPP4 genetic variants influence baseline PSA levels, especially in men aged between 60 and 69.

Patients with diabetes have been reported to be at an increased risk for cancers of the pancreas, liver, and colon; however, recent studies have suggested that men with diabetes are at a decreased risk for prostate cancer. Previous studies have found that obese men have lower serum prostate-specific antigen (PSA) concentrations than do non-obese men. Further understanding of how obesity and diabetes affect the PSA concentration may improve our ability to detect clinically relevant prostate tumors. This study examined the relationships among serum PSA level, obesity, and diabetes in apparently healthy Japanese males. We analyzed the baseline data from 2,172 Japanese males (age, 56.8 ± 6.1 years [mean ± SD]) who participated in the Japan Multi-Institutional Collaborative Cohort Study. Diabetes was defined as the presence of both a hemoglobin A1c (JDS) of ≥6.1% and a fasting plasma glucose level of ≥126 mg/dL, or a positive medical history. After adjusting for age, the PSA levels were elevated among males with a higher normal BMI (ranging from 23.0 to 24.9) and lowered among men with a BMI of ≥25.0. In the stratified analysis, these significant differences in BMI categories were absent among diabetics. The mean PSA levels were significantly lower in diabetics than in non-diabetics among subjects aged 60 and over. Our findings suggest that the pre-overweight men had increased PSA levels, and the diabetes was associated with a reduction of PSA levels in elderly.

Helicobacter pylori (H. pylori) has expanded to infect about half the world’s population. Although there were many studies on the prevalence of H. pylori infection for defined areas in the 1990s throughout the world, there were only limited sources tracking its latest prevalence among large populations. In the present study, we estimated the prevalence of H. pylori among the inhabitants of Nagoya, an urban area of Japan. Study subjects were 5,167 participants (1,467 males and 3,700 females) aged 35 to 69 years from the Daiko Study, a part of the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). A urinary anti-H. pylori antibody was used to detect H. pylori infection. The history of eradication treatments for H. pylori infection was obtained using self-administered questionnaires. The prevalence detected by the urinary test included 19.6% (95% confidence interval; 16.8–22.6%) for those aged 35–39 years, 25.8% (23.5–28.2%) for 40–49 years, 39.4% (36.8–42.1%) for 50–59 years, 50.3% (47.8–52.7%) for 60–69 years, and 36.4% (35.1–37.7%). Among 5,167 participants, 266 (5.1%) stated that they had received an eradication treatment. Since 167 subjects with negative urinary tests replied that they had been seropositive for H. pylori in the past, they were included among the ever-infected inhabitant group. Consequently, the overall rate of those with a history of persistent infection was 39.6% (38.3–40.9%). The prevalence of H. pylori infection observed in Nagoya seemed to be lower than the corresponding prevalence reported in other studies of Japan. That lower rate might be due to the reduced exposure from improved urban sanitary conditions.