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This population-based study aimed to evaluate the association between bowel habits from midlife and dementia. This was a cohort study using certification records for national long-term care insurance in Japan. Participants aged 50 to 79 years who reported bowel habits from eight districts within the Japan Public Health Center-based Prospective Study (JPHC Study) were followed from 2006 to 2016 for incident dementia. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for men and women separately using Cox proportional hazards models accounting for various lifestyle factors and medical histories. Among 19,396 men and 22,859 women, 1889 men and 2685 women were diagnosed with dementia. In men, the multivariable-adjusted HRs compared with bowel movement frequency (BMF) of once/day were 1.00 (95% CI: 0.87–1.14) for twice/day or more, 1.38 (1.16–1.65) for 5–6 times/week, 1.46 (1.18–1.80) for 3–4 times/week, and 1.79 (1.34–2.39) for <3 times/week (P for trend <0.001). In women, the corresponding HRs were 1.14 (0.998–1.31), 1.03 (0.91–1.17), 1.16 (1.01–1.33), and 1.29 (1.08–1.55) (P for trend = 0.043). Harder stool was associated with higher risk (P for trend: 0.0030 for men and 0.024 for women), with adjusted HRs compared to normal stool of 1.30 (1.08–1.57) for hard stool and 2.18 (1.23–3.85) for very hard stool in men, and 1.15 (1.002–1.32) and 1.84 (1.29–2.63) in women. Lower BMF and harder stool were each associated with higher risk of dementia. [ABSTRACT FROM AUTHOR]

Background: Evidence of the association between chronic low-grade inflammation, as reflected by C-reactive protein (CRP) measurements, and cancer risk is equivocal. Specifically, few studies have examined this in uncommon cancers and Asian populations.Methods: We utilised a case-cohort design consisting of multi-types of cancer (N = 3608), and a random subcohort (N = 4432) in a Japanese large population-based study, with a median follow-up time of 15.6 years, and measured baseline plasma CRP using high sensitivity assay. The hazard ratios (HRs) were estimated using weighted Cox proportional hazards methods.Results: The multivariable-adjusted HR (95% confidence interval) for the top quartile of CRP was 1.28 (1.11‒1.48) (Ptrend < 0.001) for overall cancer compared to the bottom quartile of CRP. Among site-specific cancers, higher CRP levels were associated with an increased risk of colorectal, lung, breast, biliary tract, and kidney cancer, and leukaemia. These positive associations remained among participants after >3 years' follow-up. Furthermore, subgroup analyses for overall cancer robustly showed a positive association with CRP levels, regardless of sex and obesity.Conclusion: Our consistent findings suggested that chronic low-grade inflammation measured by CRP is associated with the risk of cancer. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To assess the predictive ability of a genetic risk score for the incidence of Type 2 diabetes in a general Japanese population. Methods: This prospective case–control study, nested within a Japan Public Health Centre‐based prospective study, included 466 participants with incident Type 2 diabetes over a 5‐year period (cases) and 1361 control participants, as well as 1463 participants with existing diabetes and 1463 control participants. Eleven susceptibility single nucleotide polymorphisms, identified through genome‐wide association studies and replicated in Japanese populations, were analysed. Results: Most single nucleotide polymorphism loci showed directionally consistent associations with diabetes. From the combined samples, one single nucleotide polymorphism (rs2206734 at CDKAL1) reached a genome‐wide significance level (odds ratio 1.28, 95% CI 1.18–1.40; P = 1.8 × 10–8). Three single nucleotide polymorphisms (rs2206734 in CDKAL1, rs2383208 in CDKN2A/B, and rs2237892 in KCNQ1) were nominally significantly associated with incident diabetes. Compared with the lowest quintile of the total number of risk alleles, the highest quintile had a higher odds of incident diabetes (odds ratio 2.34, 95% CI 1.59–3.46) after adjusting for conventional risk factors such as age, sex and BMI. The addition to the conventional risk factor‐based model of a genetic risk score using the 11 single nucleotide polymorphisms significantly improved predictive performance; the c‐statistic increased by 0.021, net reclassification improved by 6.2%, and integrated discrimination improved by 0.003. Conclusions: Our prospective findings suggest that the addition of a genetic risk score may provide modest but significant incremental predictive performance beyond that of the conventional risk factor‐based model without biochemical markers. [ABSTRACT FROM AUTHOR]

Objective To investigate the association between serum total cholesterol ( TC) and suicide using a large general population cohort with long follow-up times. Method Analyses included 16 341 men and 28 905 women aged 40-69 from the Japan Public Health Center-based Prospective Study followed from 1990 to 2012. TC levels were defined per clinical guidelines: low (<4.66 mmol/l [180 mg/dl]), normal (4.66-5.70 mmol/l [180-220 mg/dl]), and high (≥5.70 mmol/l [220 mg/dl]). Cox proportional hazards regression models were used to determine hazard ratios ( HR) and confidence intervals ( CI) for suicide according to TC level. Mean follow-up time was 19 years for men and 20 years for women. Results There were 185 suicides (men: 107; women: 78) during follow-up. Compared to women with normal TC, women with high TC had a significantly increased risk of suicide ( HR = 1.90, 95% CI, 1.13-3.19). Incremental increases (0.26 mmol/l [10 mg/dl]) of low-density lipoprotein ( HR = 1.11, 95% CI, 1.02-1.21) and non-high-density lipoprotein cholesterol ( HR = 1.09, 95% CI, 1.01-1.18) were also associated with increased risk of suicide in women. There was no association between TC levels, or lipid fractions, and suicide in men. Conclusion High TC levels may be associated with an increased risk of suicide in women. [ABSTRACT FROM AUTHOR]

Summary: This study assessed the effects of physical activity on a 10-year incidence of self-reported vertebral fractures in adult women of a large Japanese cohort. Medium levels of strenuous activity and long-duration sedentary activity were associated with a lower incidence of vertebral fractures; association patterns appear to be different from hip fractures. Introduction: Physical activity helps prevent hip fracture, but little is known about the longitudinal association between physical activity and vertebral fractures. The purpose of this study was to evaluate the effects of physical activity on the 10-year incidence of symptomatic vertebral fractures using data from the Japan Public Health Center-based Prospective Study. Methods: Baseline studies were conducted in 1993-1994, and the follow-up study was conducted 10 years later. We analyzed 23,757 women aged 40-69 years. At baseline, physical activity was assessed as a predictor by using a questionnaire. Subjects were asked to report vertebral fractures that occurred during the 10-year follow-up period. Relative risks (RRs) adjusted for confounders were estimated by multiple logistic regression analysis. Results: The 10-year cumulative incidence of vertebral fractures was 0.67 %. Those who engaged in strenuous physical activity of <1 h/day had a significantly lower incidence of vertebral fractures than those who did not engage in such activity (RR = 0.52, 95 % CI 0.28-0.97), while those engaged in such activity ≥1 h/day did not (RR = 0.82, 95 % CI 0.58-1.14). Long-duration sedentary activity was associated with a low incidence of vertebral fractures ( P for trend = 0.0002), but the frequencies of sports activities and metabolic equivalents were not ( P for trend = 0.0729 and 0.4341, respectively). Conclusions: Strenuous activity and sedentary activity are associated with the incidence of vertebral fractures, although the association may not be linear. The pattern of association between physical activity and vertebral fractures appears to be different from that of hip fractures. [ABSTRACT FROM AUTHOR]

Seafood/fish intake has been regarded as a protective factor for coronary heart disease (CHD), while smoking is a strong risk factor. To examine whether associations between smoking and risk of CHD are modified by seafood/fish intake, we studied 72,012 Japanese men and women aged 45–74 years who completed 2 food frequency questionnaires, 5 years apart, during the period 1995–2009. After 878,163 person-years of follow-up, 584 incident cases of CHD (101 fatal and 483 nonfatal), including 516 myocardial infarctions, were documented. There was a clear dose-response association between smoking and CHD risk among subjects with a low seafood/fish intake (<86 g/day) but not among those with a high seafood/fish intake (≥86 g/day). Compared with never smokers, the multivariable hazard ratios in light (1–19 cigarettes/day), moderate (20–29 cigarettes/day), and heavy (≥30 cigarettes/day) smokers were 2.39 (95% confidence interval (CI): 1.60, 3.56), 2.74 (95% CI: 1.90, 3.95), and 3.24 (95% CI: 2.12, 4.95), respectively, among low seafood/fish eaters and 1.13 (95% CI: 0.64, 1.99), 1.29 (95% CI: 0.95, 2.04), and 2.00 (95% CI: 1.18, 3.51), respectively, among high seafood/fish eaters. Compared with heavy smokers with a low seafood/fish intake, light smokers with a high seafood/fish intake had substantially reduced risk of CHD (hazard ratio = 0.57, 95% CI: 0.32, 0.98). High seafood/fish intake attenuated the positive association between smoking and risk of CHD. [ABSTRACT FROM PUBLISHER]

Background:Colorectal cancer (CRC) incidence rate increased rapidly in Japan between the 1950s and 1990s. We examined the association between rice intake and CRC risk in comparison with bread, noodles and cereal among Japanese adults enrolled in the Japan Public Health Center-based prospective Study.Methods:A total of 73 501 Japanese men and women were followed-up from 1995 to 1999 until the end of 2008 for an average of 11 years. During 801 937 person-years of follow-up, we identified 1276 incident cases of CRC. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CRC for rice, noodle, bread and cereal intake were calculated by Cox proportional hazards model.Results:Overall, no significant association was observed for the highest quartile of rice intake compared with the lowest and the risk of CRC and its subsites in men (HR, 0.77; 95% CI, 0.56-1.07) and women (HR, 1.10; 95% CI, 0.71-1.68). However, a non-significant inverse trend was observed between rice intake and rectal cancer in men. No clear patterns of association were observed in bread, noodle and cereal intake.Conclusion:Our findings suggest that the consumption of rice does not have a substantial impact on the risk of CRC in the Japanese population. [ABSTRACT FROM AUTHOR]

Summary The present study examined the association of denture quality and health-related quality of life (HRQoL) in patients with removable dentures. In a study of 171 consecutive patients with removable partial dentures or complete dentures (mean age: 68·0 ± 9·3 years) at a university-based prosthodontic clinic, dentists rated two aspects of denture quality (stability and aesthetics) using a 100-mm visual analog scale (VAS). HRQoL was evaluated using the mental and physical component summary (MCS and PCS) scores of the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36). Oral health-related quality of life (OHRQoL) was evaluated using the Oral Health Impact Profile-Japanese version (OHIP-J). The associations among denture quality, OHRQoL, and HRQoL were examined by linear regression models. Bivariable linear regression analyses revealed that denture stability was significantly associated with the SF-36 MCS [regression coefficient = 0·52 for a 10-unit increase in denture stability on a 0-100 VAS, 95% confidence interval (CI): 0·03-1·00, P = 0·04], but not with the PCS (0·11, 95% CI: −0·49 to 0·70). Denture aesthetics was not related to the PCS or the MCS (0·22, 95% CI: −0·44 to 0·88 or 0·07, 95%CI: −0·47 to 0·62). When OHIP-J was added to the regression model, this variable was substantially and significantly associated with the MCS and PCS summary scores; in addition, the regression coefficient for denture quality decreased in magnitude and was statistically nonsignificant in all analyses. The quality of removable dentures had a minimal effect on HRQoL in patients with removable dentures, and this association was mediated by OHRQoL. [ABSTRACT FROM AUTHOR]

IL-17 has an important role in the host defense against extracellular pathogens and the pathophysiology of autoimmune diseases. This study retrospectively examined the impact of a single-nucleotide polymorphism (rs2275913, G197A) in the IL-17 gene of a total 510 recipients with hematologic malignancies and their unrelated donors on the clinical outcomes in HLA-matched myeloablative (discovery study) and nonmyeloablative (validation study) BMT through the Japan Marrow Donor Program (JMDP). In the discovery study, the presence of a 197A genotype in the recipient resulted in a higher incidence of grades II-IV acute GVHD (hazard ratio (HR), 1.87; 95% confidence interval (CI), 1.23-2.85; P=0.004). The donor IL-17A genotype did not significantly influence the transplant outcomes. The validation study showed a trend toward an association of the recipient 197A genotype with an increased risk of grades III-IV acute GVHD (HR, 5.84; 95% CI, 0.75-45.72; P=0.09), as well as a significantly increased risk for chronic GVHD (HR, 3.86; 95% CI, 1.29-11.59; P=0.02). These results suggest an association of the 197A genotype in the recipient side with the development of acute GVHD. [ABSTRACT FROM AUTHOR]

Summary Introduction: T-helper cell type 1 (Th1) polarization of the immune response has been documented in patients with chronic immune thrombocytopenia (ITP). Interleukin (IL)-10 is the most important factor regulating Th1 and T-helper type 2 cytokine synthesis. This study evaluated the impact of IL-10 polymorphisms on both susceptibility to, and severity of, chronic ITP. Methods: We analyzed -1082(G/A), -812(C/T), and -592(C/A) IL-10 polymorphisms in 90 patients with adult chronic ITP and 202 race- and sex-matched healthy controls. Results: No significant differences in the genotype or haplotype frequencies were observed between the patient with chronic ITP and the control group. However, more patients with the -592AA genotype showed a severe thrombocytopenic state (platelet count <10 × 109/l) than those with the -592CC/CA genotypes (44.1% vs. 19.6%, P = 0.01). Furthermore, more patients with the ATA/ATA haplotype showed a severe thrombocytopenic state than those without the ATA/ATA haplotype (44.1% vs. 19.6%, P = 0.01). Conclusion: According to our data, patients with low producer type of IL-10 polymorphisms have more severe thrombocytopenia, suggesting that IL-10 gene polymorphisms may reflect the severity of ITP. [ABSTRACT FROM AUTHOR]

We retrospectively audited the performance of the commercial kit in use in our laboratory for the detection of Mycobacterium tuberculosis complex (MTBC) and found the sensitivity to be unacceptably low at 69% (52/75). We developed an in-house end-point polymerase chain reaction (PCR) detecting IS6110, an IS-like element of MTBC, and achieved a sensitivity of 90% (66/73) with the same DNA samples, re-emphasising the poor performance of the commercial kit. In order to avoid specificity issues surrounding gel-based PCR, we developed a probe-based real-time PCR assay with an internal control and achieved a sensitivity of 84%, specificity of 97% and diagnostic odds ratio (DOR) of 207. The evaluation was performed on clinically requested samples, so we expect the performance of the assay in real life to match the data from this evaluation. Centers for Disease Control and Prevention (CDC) guidelines recommending nucleic acid tests for the investigation of possible cases of tuberculosis are expected to promote the use of molecular assays. It is important that clinical laboratories do not assume that assays, in-house or commercial, will perform well or that they will continue to perform well. Audit at regular intervals is necessary to maintain confidence and to demonstrate that the assay works to specification in the real test population. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, e75-e81 (2012) Abstract Aims We investigated the value of persistent fasting hyperglycaemia as assessed by repeated elevated fasting plasma glucose in predicting the progression to diabetes. Methods A retrospective cohort study was conducted from 1998 to 2006 inclusive among 7929 persons (37 742 person-years), with a mean age of 53.0 years at baseline. The cumulative incidence of diabetes was measured. A baseline and follow-up fasting plasma glucose were categorized as normal fasting glucose (< 5.56 mmol/l), or impaired fasting glucose (5.56-6.94 mmol/l). Results The cumulative incidence and incidence density of diabetes were 3.5% (275 cases) and 7.3 per 1000 person-years over a mean follow-up period of 4.8 years. The cumulative incidence of diabetes among subjects with impaired fasting glucose at both previous examinations (persistent impaired fasting glucose) was 30.4% (222/1518) compared with 0.6% (15/5063) of those with normal fasting glucose at both baseline and initial follow-up. The hazard ratios to develop diabetes, adjusted for possible confounders, was 37.10 (95% CI, 21.6-63.7) for persistent impaired fasting glucose versus persistent normal fasting glucose. Persistent impaired fasting glucose predicted diabetes at 80.7% (222/275) sensitivity and 83.1% (6358/7654) specificity, whereas first baseline impaired fasting glucose only predicted diabetes at 86.9% (239/275) sensitivity and 74.9% (5730/7654) specificity. The model using both previous fasting plasma glucose levels had a greater AUROC (area under receiver operating characteristic) than that using first baseline fasting plasma glucose only (0.92 vs. 0.88; P < 0.001). Conclusions Repeated measurements of fasting plasma glucose better predicts incidence of diabetes than a single test. In particular, persistent fasting hyperglycaemia adds more substantial precision to the prediction of future diabetes than transient impaired fasting glucose. This combination is cost efficient and may be practical for early detection of high-risk individuals. [ABSTRACT FROM AUTHOR]

Prospective evidence is inconsistent regarding the association between vegetable/fruit intake and the risk of gastric cancer. This pooled analysis of data from four large prospective studies in Japan suggests that vegetable intake reduces gastric cancer risk, especially the risk of distal gastric cancer among men.Background Prospective evidence is inconsistent regarding the association between vegetable/fruit intake and the risk of gastric cancer. Methods In an analysis of original data from four population-based prospective cohort studies encompassing 191 232 participants, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of gastric cancer incidence according to vegetable and fruit intake and conducted a meta-analysis of HRs derived from each study. Results During 2 094 428 person-years of follow-up, 2995 gastric cancer cases were identified. After adjustment for potential confounders, we found a marginally significant decrease in gastric cancer risk in relation to total vegetable intake but not total fruit intake: the multivariate-adjusted HR (95% CI; P for trend) for the highest versus the lowest quintile of total vegetable intake was 0.89 (0.77–1.03; P for trend = 0.13) among men and 0.83 (0.67–1.03; P for trend = 0.40) among women. For distal gastric cancer, the multivariate HR for the highest quintile of total vegetable intake was 0.78 (0.63–0.97; P for trend = 0.02) among men. Conclusion(s) This pooled analysis of data from large prospective studies in Japan suggests that vegetable intake reduces gastric cancer risk, especially the risk of distal gastric cancer among men. [ABSTRACT FROM PUBLISHER]

“We assessed the associations between BMI and breast cancer incidence by a pooled analysis from eight representative large-scale cohort studies in Japan. The increased risk of postmenopausal and premenopausal breast cancer was found among women with higher BMIs. Body mass in Asian women might have opposite effects on premenopausal breast cancer compared with Western women”.Background A positive association between body mass index (BMI) and breast cancer risk among postmenopausal women has been reported, and a weak inverse association has been suggested among premenopausal women from studies in the Western population. The effects of BMI on breast cancer have remained unclear among the Asian population, especially in premenopausal women. Methods We assessed the associations between BMI and breast cancer incidence by a pooled analysis from eight representative large-scale cohort studies in Japan. Cancer incidence was mainly confirmed through regional population-based cancer registries and/or through active patient notification from major local hospitals. Breast cancer was defined as code C50 according to ICD10. Pooled estimates of the hazard ratios (HRs) and 95% confidence interval (CIs) for breast cancer were calculated using random-effects models. Results Analytic subjects were 183 940 women, 1783 of whom had breast cancer during 2 194 211 person-years of follow-up. A positive association between BMI and the risk of postmenopausal breast cancer was observed (trend P < 0.001). The HRs for premenopausal breast cancer were 1.05 (95% CI 0.56–1.99), 1.07 (95% CI 0.76–1.52), 0.91 (95% CI 0.64–1.30), 1.15 (95% CI 0.76–1.73), 1.45 (95% CI 0.71–2.94), and 2.25 (95% CI 1.10–4.60), respectively, in BMIs of <19, 19 to <21, 21 to <23, 25 to <27, 27 to <30, and ≥30 kg/m2. These results were not substantially altered after excluding the patients who were diagnosed with breast cancer in the first 2 years of follow-up. Conclusions The increased risk of postmenopausal breast cancer among women with higher BMIs was confirmed in Japanese. A borderline-significant positive association between BMI and premenopausal breast cancer was observed, suggesting that body mass in Asian women might have opposite effects on breast cancer compared with Western women. [ABSTRACT FROM AUTHOR]