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The Japanese government's 2013 suspension of its proactive recommendation for Human papillomavirus (HPV) vaccination resulted in low HPV vaccination coverage and was unique. However, data on awareness and knowledge of HPV vaccines in the general population was limited. Here, to investigate more recent awareness and knowledge of HPV vaccines by age, gender, and socioeconomic status, we used data from the INFORM Study 2020, a nationally representative cross-sectional survey of self-administered questionnaires with 1,998 Japanese individuals aged 20 to 59 years. We found that 47.5% of females and 21.0% of males had heard of HPV, and 33.6% of females and 16.8% of males had knowledge of HPV vaccine efficacy. After adjusting for potential confounders, females aged 50–54 years were more likely to be aware of HPV than females aged 20–24 (AOR, 2.02, 95%CI: 1.12–3.65). Females (AOR, 2.13, 95%CI: 1.48–3.07) and males (AOR, 1.64, 95%CI: 1.03–2.59) with higher education had more awareness than those with less education. Females with higher education had more knowledge about HPV vaccine efficacy than those with less education (AOR, 1.70; 95%CI: 1.16–2.50). We found a generally low level of awareness and knowledge about HPV vaccines in Japan, which might be attributable to the suspension of proactive recommendations. Additionally, we identified disparities in awareness and knowledge by age, gender, socioeconomic status, and health literacy. Enhancing HPV awareness and understanding of HPV vaccines and implementing targeted efforts for specific subpopulations within Japan after the resumption of proactive recommendation for HPV vaccines, are imperative. [ABSTRACT FROM AUTHOR]

Older patients with cancer are less likely to express their treatment preferences than younger patients. Question prompt lists (QPLs) facilitate communication between patients and physicians. Geriatric assessment (GA) is recommended when older patients with cancer make treatment decisions. This study estimated the effect size of a shared decision-making (SDM) support program combining QPLs with GA in terms of patients' subjective evaluation of the SDM process for a future definitive randomized controlled trial. We also evaluated the number and quality of aging-related communication during consultations, and feasibility and acceptability of the study for exploratory purposes. This is a pilot study with randomized allocation and blind evaluation. Patients aged 65 years or older at the National Cancer Center Hospital, Tokyo, Japan, scheduled to discuss the changes of their treatment, were randomly assigned in a 1:1 ratio to the SDM support program or usual care. This program consisted of 30–60 min of face-to-face coaching, with QPLs and GA provided before the coaching. As the primary endpoint, the decisional conflict scores given by the patients immediately after the consultation were compared between the two groups. For the secondary endpoints, the number and quality of aging-related communications during the consultations were assessed by evaluators (blinded) using audio-recordings. Adherence, burden, and usefulness were assessed for evaluating feasibility and acceptability of the SDM support program. Forty patients were enrolled. All patients completed the GA questionnaire, for which 70% did not require any individual assistance. Answering the questionnaires took approximately 11 min. The decisional conflict scores were mean [ standard deviation (SD) ]: 19.3 [10.8] vs. 18.0 [11.1] (effect size: Cohen's d = 0.12) for the SDM support program and usual care groups, respectively. The number of aging-related communications during the consultation for the new treatment was higher in the SDM support program group than the usual care (mean [ SD ]: 3.3 [1.2] vs. 2.2 [1.5], effect size: cohen's d = 1.32). Patients felt that the SDM support program was useful but not burdensome or difficult. The SDM support program was considered useful and feasible for older patients and able to facilitate communication regarding aging-related concerns. The study protocol was registered on September 23, 2020, in the UMIN Clinical Trials Registry (UMIN000041867). [ABSTRACT FROM AUTHOR]

Background: Soy is commonly consumed in east Asian countries and is suggested to reduce colorectal cancer (CRC) risk. However, results from epidemiologic studies are inconsistent, despite the anti-inflammatory and antiproliferative properties of soy isoflavones and soy protein.Objective: We evaluated the association between soy isoflavones and soy protein and CRC risk using 4 prospective cohort studies from China and Japan.Methods: Data were pooled from the Shanghai Women's Health Study (SWHS), Shanghai Men's Health Study (SMHS), Japan Public Health Center-based Prospective Study Cohort 1 (JPHC1), and Cohort 2 (JPHC2). Cox proportional hazards models estimated HRs and corresponding 95% CIs for the association of soy protein and isoflavone intake with CRC risk. The study included 205,060 individuals, among whom 2971 were diagnosed with incident CRC over an average follow-up of 12.7 y.Results: No statistically significant associations with CRC risk were observed for soy protein or isoflavone intake. No association was observed among ever smokers consuming higher isoflavones (HRisoflavones: 0.83; 95% CI: 0.68, 1.00) and soy protein (HRsoy protein: 0.81; 95% CI: 0.39, 1.10). However, risk reductions were observed among premenopausal women with a body mass index [BMI (kg/m2)] <23.0 at baseline for higher isoflavone (HRisoflavones: 0.58, 95% CI: 0.34, 0.98).Conclusions: No evidence for an overall reduction in CRC risk by increasing soy food intake (i.e., protein or isoflavones) was observed. However, the association between soy and CRC risk may vary by BMI, smoking, and menopausal status among women. Future investigations are needed to further understand the biologic mechanisms observed. [ABSTRACT FROM AUTHOR]

Many studies have suggested that fish intake is associated with protection from risk of atherosclerotic diseases; however, this association with aortic diseases has not been elucidated worldwide. We hypothesized that fish intake is inversely associated with mortality from aortic diseases (aortic dissection and aneurysm). The study was conducted as a pooled analysis of original data from a maximum of 8 cohort studies, comprising a total of 366,048 community-based men and women who had no history of cardiovascular disease or cancer. In each cohort, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality from aortic dissection, aneurysm and total aortic disease according to the frequency of fish intake and estimated summary HRs derived from each study. Nonlinear inverse associations were found between fish intake and total aortic disease. Compared with persons who ate fish 1–2 times/week, persons who seldom ate fish had higher mortality from total aortic disease (multivariable-adjusted pooled HR = 1.93; 95% CI, 1.13–3.31). Higher mortality was not seen in those who ate fish 1–2 times/month. A similar pattern was observed for aortic dissection. Regarding aortic aneurysm, both persons who seldom ate fish and those who ate fish 1–2 times/month had higher mortality (HR = 1.99; 95% CI, 0.90–4.40 and HR = 1.86; 95% CI, 0.87–3.98, respectively). Persons who seldom ate fish had higher mortality from aortic dissection, aneurysm, and total aortic diseases. • Fish intake may have a protective role for developing aortic diseases, but no epidemiological studies exist on this issue. • In this pooled analysis, we first identified that low fish intake was a risk factors for mortality from aortic diseases. • A threshold was suggested between the seldom and 1–2 times/month categories of fish intake. [ABSTRACT FROM AUTHOR]

Summary Background & aims Cruciferous vegetables contain isothiocyanates, which effectively reduce inflammation and oxidative stress related to chronic diseases, inhibit the bioactivation of procarcinogens, and enhance the excretion of carcinogens. However, at present, no large cohort studies have investigated the effect of cruciferous vegetable on mortality. We aimed to examine the association between cruciferous vegetable intake and all-cause mortality, namely cancer, heart disease, cerebrovascular disease, and injuries, in a large cohort study conducted between 1990 and 1993, in Japan. Methods The analysis included 88,184 participants (age: 45–74 years) with no history of cancer, myocardial infarction, and stroke. Participants were tracked for a median of 16.9 years, during which 15,349 deaths were occurred. The association between cruciferous vegetable intake and risk of all-cause and cause-specific mortality was determined by Cox proportional hazard regression analysis to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs), after adjustment for potential confounding factors. Results An inverse association was found between cruciferous vegetable intake and total mortality in both gender. HRs (95% CI) for all-cause mortality in the highest compared to the lowest quintile were 0.86 (0.80, 0.93) for men (P = 0.0002 for trend) and 0.89 (0.81, 0.98) for women (P = 0.03 for trend). Cruciferous vegetable intake was associated with lower cancer mortality in men, as well as with heart disease-, cerebrovascular disease-, and injury-related mortality in women. Conclusions This prospective study suggests that a higher cruciferous vegetables intake is associated with reduced risk of all-cause mortality. [ABSTRACT FROM AUTHOR]

Various guidelines recommend geriatric assessment (GA) for older adults with cancer, but it is not widely implemented in daily practice. This study uses an implementation framework to comprehensively and systematically identify multi-level barriers and facilitators to implementing GA in daily oncology practice. We conducted 16 semi-structured interviews with healthcare providers in 10 designated cancer hospitals in Japan, using purposive and convenience sampling. The Consolidated Framework for Implementation Research (CFIR) was used to guide collection and analysis of interview data following a deductive content analysis approach with consensual qualitative research methods. After coding the interview data, ratings were assigned to each CFIR construct for each case, reflecting the valence and strength of each construct relative to implementation success. Then, those constructs that appeared to distinguish between high-implementation hospitals (HI) where GA is routinely performed in daily practice and low-implementation hospitals (LI) where GA is performed only for research purposes or not at all were explored. Of the 24 CFIR constructs assessed in the interviews, 15 strongly distinguished between HI and LI. In HI, GA was self-administered (Adaptability), or administered via a mobile app with interpretation (Design Quality and Packaging). In HI, healthcare providers were strongly aware of the urgent need to change practice for older adults (Tension for Change) and recognized that GA was compatible with existing workflow as part of their jobs (Compatibility), whereas in LI, they did not realize the need to change practice, and dismissed GA as an extra burden on their heavy workload. In HI, usefulness of GA was widely recognized by healthcare providers (Knowledge & Beliefs about the Intervention), GA had a high priority (Relative Priority) and had strong support from hospital directors, managers, and nursing chiefs (Leadership Engagement), and multiple stakeholders were successfully engaged, including nurses (Key Stakeholders), peer doctors (Opinion Leaders), and those who drive implementation of GA (Champions). These findings suggest that successful implementation of GA should focus on not only individual beliefs about the usefulness of GA and the complexity of GA itself, but also organizational factors related to hospitals and the engagement of multiple stakeholders. [ABSTRACT FROM AUTHOR]

Summary Background & aims A finding between dietary pattern and cancer may provide visions beyond the assessment of individual foods or nutrients. We examined the influence of dietary pattern with colorectal cancer (CRC) among a Japanese population. Methods A total of 93,062 subjects (43,591 men, 49,471 women) who participated in the Japan Public Health Center-based Prospective Study were followed from 1995–1998 to the end of 2012, during which 2482 cases of CRC (1514 men, 968 women) were newly identified. Dietary data was obtained from a validated food-frequency questionnaire between 1995 and 1998. Results Three dietary pattern was derived from principal components factor: prudent, westernized, and traditional pattern. After controlled for potential confounders, the prudent pattern showed a decreased association of CRC risk in men (HR for highest quintile vs lowest: 0.85; 95% CI: 0.72–1.00; P trend <0.05), slightly more strongly with distal colon cancer ( P trend <0.05); but an increased risk of rectal cancer in women ( P trend <0.05). The westernized pattern showed a significant positive linear trend for colon ( P trend <0.05) and distal cancer ( P trend <0.05) in women. There was no apparent association of traditional Japanese dietary pattern on the overall or any specific sites risk of CRC. Conclusions A prudent dietary pattern showed an inverse association with CRC risk in men, and a westernized pattern was related with a higher risk of colon and distal cancer in women. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled studies have investigated the short-term effect of soy product intake on blood pressure (BP) in normotensive people. To our knowledge, no prospective studies exist on the effect of habitual intake of fermented soy products, separate from total soy products, on BP in the general population.Objective: We examined the association between the habitual intake of soy products, including fermented soy products, and the development of high BP during a 5-y period among participants in a population-based prospective cohort study in Japan.Methods: The study included normotensive participants aged 40-69 y at baseline (926 men and 3239 women) who completed 2 questionnaires and whose BP was measured at the baseline survey between 1993 and 1994 and the 5-y follow-up in the Japan Public Health Center-Based Prospective Study Cohort II. The intake of soy products was assessed with a food-frequency questionnaire. High BP was defined as systolic blood pressure ≥130 mm Hg, diastolic blood pressure ≥85 mm Hg, or antihypertensive medication use. ORs and 95% CIs of high BP by frequency of soy products (miso, natto, and tofu) consumption, intake of total and fermented soy products, and intake of isoflavones from total and fermented soy products were estimated with the use of multiple logistic regression analysis.Results: Multivariable-adjusted ORs of high BP for the highest compared with the lowest tertile of total and fermented soy product intake were 1.03 (95% CI: 0.84, 1.25; P-trend = 0.786) and 0.72 (95% CI: 0.56, 0.92; P-trend = 0.009), respectively. The frequency of nonfermented soy product (tofu) intake was not associated with the development of high BP (P-trend = 0.597).Conclusions: The intake of fermented soy products, but not total or nonfermented soy products, was inversely associated with developing high BP in men and women with normal BP. [ABSTRACT FROM AUTHOR]

Background: Cruciferous vegetables, a rich source of isothiocyanates, have been reported to lower the risk of several types of cancer, including lung cancer. However, evidence from prospective observations of populations with a relatively high intake of cruciferous vegetables is sparse.Objective: We investigated the association between cruciferous vegetable intake and lung cancer risk in a large-scale population-based prospective study in Japan.Methods: We studied 82,330 participants (38,663 men; 43,667 women) aged 45-74 y without a past history of cancer. Participants were asked to respond to a validated questionnaire that included 138 food items. The association between cruciferous vegetable intake and lung cancer incidence was assessed with the use of Cox proportional hazard regression analysis to estimate HRs and 95% CIs (with adjustments for potential confounding factors).Results: After 14.9 y of follow-up, a total of 1499 participants (1087 men; 412 women) were diagnosed with lung cancer. After deleting early-diagnosed cancer and adjusting for confounding factors, we observed a nonsignificant inverse trend between cruciferous vegetable intake and lung cancer risk in men in the highest compared with the lowest quartiles (multivariate HR: 0.85; 95% CI: 0.69, 1.06; P-trend = 0.13). Stratified analysis by smoking status revealed a significant inverse association between cruciferous vegetable intake and lung cancer risk among those who were never smokers and those who were past smokers after deleting lung cancer cases in the first 3 y of follow-up [multivariate HR for never smokers: 0.49 (95% CI: 0.27, 0.87; P-trend = 0.04); multivariate HR for past smokers: 0.59 (95% CI: 0.35, 0.99; P-trend = 0.10)]. No association was noted in men who were current smokers and women who were never smokers.Conclusion: This study suggests that cruciferous vegetable intake may be associated with a reduction in lung cancer risk among men who are currently nonsmokers. [ABSTRACT FROM AUTHOR]

In July 2019, in accordance with the Medical Information Distribution Service Manual for Guideline Development 2014, which was based on the Grading of Recommendations Assessment, Development and Evaluation approach, the Japanese Society of Medical Oncology (JSMO) and the Japan Society of Clinical Oncology (JSCO) published clinical practice guidelines (CPGs) on chemotherapy and other drug therapies for older patients with cancer (JSMO-JSCO CPGs). In September 2020, at one year after the publication of these guidelines, a survey was conducted to determine the extent to which they had been disseminated to JSMO and JSCO members and implemented in daily practice. This nationwide, cross-sectional, web-based survey was conducted with JSMO and JSCO members. We surveyed the participants' overall awareness of the JSMO-JSCO CPGs, and their knowledge about, attitudes toward, and perceived barriers to adherence to each recommendation using validated questionnaires based on theoretical frameworks used in previous studies (Awareness to Adherence Model, Clinicians' Assessments of Practice Guidelines in Oncology questionnaires, and Knowledge–Attitudes–Behavior Framework). Among JSMO and JSCO members who had been informed of the survey, 1230 responded (response rate: 8.6% and 4.8%, respectively). From these respondents, 107 were excluded because they did not practice anticancer drug therapy at the time of the survey. Of the remaining 1123 eligible participants, 674 (60.0%) were aware of the JSMO-JSCO CPGs before the survey, 492 (73.0%) of whom had read all or part of the guidelines (publications 57.1%, JSMO website 34.8%, and JSCO website 14.0%). Knowledge about, attitudes toward, and barriers to adherence to each recommendation differed widely according to the clinical questions. The most commonly cited barriers were lack of awareness, lack of agreement, lack of evidence, lack of outcome expectancy, patient values and preferences, and patient factors. This survey identified different barriers to guideline adherence, including providers' knowledge, attitudes, and external factors, depending on each recommendation. Effective strategies to overcome these barriers can be expected to improve the implementation of the guideline recommendations. Based on the results of this survey, efforts should be made to promote further the use of the clinical guidelines in daily practice. [ABSTRACT FROM AUTHOR]

Background: Food sources and intakes of zinc and heme iron may differ between Western and Asian populations. However, all of the studies on the association between zinc and heme iron intakes and colorectal cancer have been conducted in Western populations. Objective: We investigated the association between zinc and heme iron intakes and colorectal cancer risk in a Japanese general population. Design: We conducted a large, population-based prospective study in 39,721 men and 45,376 women aged 45-74 y. Heme iron and zinc intakes were measured by using a validated food-frequency questionnaire in either 1995 or 1998. Results: During as many as 808,053 person-years of follow-up until the end of 2006, 1284 colorectal cancer cases were identified. In multivariate-adjusted models, zinc and heme iron intakes were not associated with colorectal cancer in either men or women. In comparison with the lowest quartile, the HRs (95% CIs) for developing colorectal cancer in the fourth quartile of zinc and heme iron intakes were 0.77 (0.58, 1.03; P-trend = 0.2) and 1.06 (0.79, 1.42; P-trend = 0.6), respectively, for men and 1.05 (0.77, 1.44; /"-trend = 0.4) and 0.88 (0.61, 1.29; F-trend = 0.4), respectively, for women. Conclusion: Our results in a Japanese population with lower intakes and different major food sources of zinc and heme iron in comparison with those of Western populations suggest that zinc and heme iron intakes are not associated with colorectal cancer. [ABSTRACT FROM AUTHOR]

Background & Aims: Fish is a rich source of n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Although consumption of fish and n-3 PUFA has been reported to protect against the development of some types of cancer, little is known about its association with hepatocellular carcinoma (HCC). Methods: We investigated the association between fish and n-3 PUFA consumption and HCC incidence (n = 398) in a population-based prospective cohort study of 90,296 Japanese subjects (aged, 45–74 y). Hazard ratios and 95% confidence intervals (CIs) for the highest vs the lowest quintile were estimated from multivariable adjusted Cox proportional hazards regression models. We also conducted subanalyses of subjects with known hepatitis B virus (HBV) or hepatitis C virus (HCV) status, and of subjects who were anti-HCV and/or hepatitis B surface antigen positive. All tests of statistical significance were 2-sided. Results: Among all subjects, consumption of n-3 PUFA-rich fish and individual n-3 PUFAs was associated inversely with HCC, in a dose-dependent manner. Hazard ratios for the highest vs lowest quintiles were 0.64 (95% CI, 0.42–0.96) for n-3 PUFA-rich fish, 0.56 (95% CI, 0.36–0.85) for EPA, 0.64 (95% CI, 0.41–0.98) for DPA, and 0.56 (95% CI, 0.35–0.87) for DHA. These inverse associations were similar irrespective of HCV or HBV status. Conclusions: Consumption of n-3 PUFA-rich fish or n-3 PUFAs, particularly EPA, DPA, and DHA, appears to protect against the development of HCC, even among subjects with HBV and/or HCV infection. [ABSTRACT FROM AUTHOR]

Background: Isoflavones are structurally similar to 17β-estradiol and may be able to prevent gastric cancer. However, there is contradictory evidence concerning the relation between the intake of soy food, which is rich in isoflavones, and gastric cancer. The association with gastric cancer might differ between isoflavones and soy foods, and research on the effects of isoflavone intake alone on gastric cancer is needed. Objective: We investigated the association between isoflavone intake and the incidence of gastric cancer. Design: We conducted a large, population-based prospective study of 39,569 men and 45,312 women aged 45-74 y. Dietary soy and isoflavone intakes were measured by using a validated food-frequency questionnaire in 1995 and 1998. Results: During 806,550 person-years of follow-up, we identified 1249 new gastric cancer cases. Isoflavone intake was not associated with gastric cancer in either men or women. Compared with the lowest quartile, the HR and 95% CI for developing gastric cancer in the fourth quartile of isoflavone intake was 1.00 (0.81, 1.24) for men and 1.07 (0.77, 1.50) for women. In a stratified analysis by exogenous female hormones (women only), however, we found an increasing trend in risk of gastric cancer associated with higher isoflavone intakes among exogenous female hormone users (P-trend = 0.03) but not for nonusers (P-interaction = 0.04). Conclusion: The current study does not support the hypothesis that higher intakes of isoflavones prevent gastric cancer in either men or women. [ABSTRACT FROM AUTHOR]

Coffee contains various compounds that have recently been reported to exert beneficial health effects. However, the conclusion of its relation with mortality has not yet been reached. In this study, we aimed to investigate the associations between coffee consumption and all-cause and cause-specific mortality in Japan. We included 37,742 participants (18,287 men and 19,455 women) aged 40-64 y without a history of cancer, myocardial infarction, or stroke at baseline in our analysis, based on the Miyagi Cohort Study initiated in 1990. The outcomes were mortality due to all causes, cardiovascular disease (CVD), and cancer. During the 10.3 y of follow-up, 2454 participants died, including 426 due to CVD and 724 due to cancer. In women, the multivariate hazard ratios (HR) (95% Cl) for all-cause mortality in participants who drank coffee never, occasionally, 1-2 cups (150-300 mL)/d, and ⩾3 cups/d were 1.00, 0.88 (0.73-1.06), 0.82 (0.66-1.02), and 0.75 (0.53-1.05), respectively (P-trend = 0.04). For CVD mortality in women, the multivariate HR (95% Cl) were 1.00, 0.56 (0.36-0.86), 0.48 (0.29-0.80), and 0.45 (0.20-1.03), respectively (P-trend = 0.006). Of the specific CVD diseases, there was a strong inverse association between coffee consumption and mortality due to coronary heart disease (CHD) in women (P-trend = 0.02) but not in men. Death due to cancer was not associated with coffee consumption in either men or women, except for colorectal cancer in women. Our results suggest that coffee may have favorable effects on morality due to all causes and to CVD, especially CHD, in women. [ABSTRACT FROM AUTHOR]

Abstract: Controversy remains as to whether the presence of the tryptophan-to-arginine (Trp64Arg) variant of the β 3-adrenergic receptor gene impedes the magnitude of body weight loss by diet and exercise intervention. The objectives of the present study were to compare the changes in body weight between carriers and noncarriers of the Trp64Arg variant before and after 6 months of diet and exercise interventions for weight loss. A total of 37 middle-aged Japanese individuals (12 carriers and 25 noncarriers of the Trp64Arg variant) participated in the study. There were no significant differences in body weight between the 2 groups at the baseline. There were significant reductions in body weight both in carriers and noncarriers, but no significant differences between the 2 groups with respect to changes in these variables. The weight changes were −2.52 kg (95% confidence interval [CI], −3.56 to −1.48) among carriers and −1.89 kg (95% CI, −2.65 to −1.13) among noncarriers, and the change in the variant carrier group minus the change in the variant noncarrier group was −0.47 (95% CI, −1.97 to 1.02). These results suggest that the presence of the Trp64Arg variant of the β 3-adrenergic receptor gene may not play a major role as a hindrance to weight reduction. [Copyright &y& Elsevier]

Background & Aims A marker is needed to identify individuals at risk for pancreatic cancer. Increases in branched-chain amino acids (BCAAs) have been associated with pancreatic cancer. We performed a prospective case–control study to study the association between plasma BCAA levels and risk of pancreatic cancer in a large cohort. Methods We conducted a nested case–control study selected from 30,239 eligible participants 40–69 years old within the Japan Public Health Center-based prospective study. Over 16.4 years, 170 newly diagnosed pancreatic cancer cases were identified. Each case was matched to 2 controls by age, gender, geographic area, and fasting time at blood collection. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer were calculated using conditional logistic regression models with adjustment for potential confounding factors. Results Increased plasma BCAA levels at baseline were associated with an increased risk of pancreatic cancer. Compared with the lowest quartile of BCAA levels, the OR in the highest quartile was 2.43 (95% CI 1.21–4.90), and the OR per 1 SD increase in BCAA levels was 1.32 (95% CI 1.05–1.67). The association was especially strong for cases with blood samples collected at least 10 years before cancer diagnosis (OR per SD 1.60, 95% CI 1.10–2.32) compared with those detected less than 10 years before diagnosis (OR per SD 1.16, 95% CI 0.86–1.57). Conclusions In an analysis of data from the Japan Public Health Center-based prospective study, we found an association between increased plasma BCAA level and increased risk of pancreatic cancer—particularly when the increase in BCAAs was observed at least 10 years before diagnosis. These findings add to the growing body of evidence for the association between BCAA levels and pancreatic cancer risk. [ABSTRACT FROM AUTHOR]

Abstract: The recent tendency of Japanese towards greater acceptance of being informed that they have cancer, along with the growing understanding and use of informed consent, appears to have improved the accuracy of self-reported cancer. To clarify the recent validity of self-reports, we measured the sensitivity and positive predictive value of self-reported cancer among a Japanese population. Using a 10-year follow-up questionnaire conducted in 2000–2004 and the cancer registry of the JPHC Study cohort (n =93,680), we calculated the sensitivity and positive predictive value of self-reported cancer diagnoses over 10 years. Sensitivity and positive predictive value of total self-reported cancer diagnoses were 53% and 60%, respectively, but varied by site, at 62% and 52% for stomach, 38% and 47% for colorectum, 57% and 46% for lung, 34% and 31% for liver, 82% and 58% for breast, and 59% and 22% for uterus, respectively. Sensitivity was considerably improved from that in the previous report (36%), which tested for 1990–1995, but was still not considered satisfactory. Self-reported diagnoses of cancer do not provide sufficient accuracy for the detection and classification of incident cancers. Our findings may be extrapolated to other Japanese populations. [Copyright &y& Elsevier]

Abstract: Unrelieved pain is a major factor that influences suicide risk among terminally ill patients, but little is known about the relationship between pain and the risk of completed suicide in the general population. We prospectively examined the association between self-reports of pain and subsequent risk of completed suicide in 26,481 men aged 40 to 79 years from the Ohsaki National Health Insurance Cohort study, a population-based, prospective cohort study initiated in 1994. On the basis of a five-item questionnaire on pain, individuals were classified as having no pain, very mild pain, mild pain, or moderate or severe pain. Completed suicide cases were documented from 1995 to 2001. During 131,027 person-years, 64 completed suicides were documented. After adjustment for covariates, the risk for completed suicide was significantly higher in the subjects with more pain. Multivariate hazard ratios (95% confidence intervals) relative to the subjects who had no pain were 1.36 (0.67–2.75), 2.11 (1.02–4.33), and 2.93 (1.34–6.42) in the subjects who had very mild pain, mild pain, and moderate or severe pain, respectively (P for trend=0.004). Stratified analysis showed that the positive association between pain and suicide risk was robust in the subjects with good health, low stress, adequate sleep, good physical activity, and no history of chronic diseases. Our results suggest that pain is associated with an increased risk of completed suicide among Japanese men. The association was consistently observed among apparently healthy subjects. [Copyright &y& Elsevier]

Abstract: The risk of suicide is well known to be increased among heavy alcohol drinkers. However, whether the risk is increased or decreased among light drinkers is still under debate. We investigated this association in a population-based sample of men in Japan. The Ohsaki Study was a population-based, prospective cohort study among Japanese adults aged from 40 to 79 years. Between October and December, 1994, 22,804 men in Miyagi Prefecture, Japan, completed a questionnaire on various health-related lifestyles, including alcohol drinking. During the subsequent 7 years follow-up, 73 participants committed suicide. We used the Cox proportional hazards regression model to estimate the hazard ratio (HR) for suicide mortality according to the quantity of alcohol consumed daily, with adjustment for potential confounders. There was a statistically significant positive and linear association between the amount of alcohol consumed and the risk of suicide: the multivariate HRs in reference to nondrinkers (95% confidence interval) were 1.2 (0.5–2.7), 1.5 (0.7–3.4), and 2.4 (1.2–4.6) in current drinkers who consumed ≤22.7g, 22.8g–45.5g, and ≥45.6g of alcohol per day, respectively (P-trend=.016). Even after the early death cases were excluded, a significant linear association was observed between alcohol consumption and the risk of suicide, with the risk of suicide also being nonsignificantly higher among the light drinkers than among nondrinkers (multivariate HR=1.7). This prospective cohort study indicated a positive linear association between alcohol consumption and the risk of suicide, and the suicide risk among the light drinkers was not decreased as compared with that in nondrinkers. [Copyright &y& Elsevier]

Purpose: Although height and body mass index (BMI) are reported to be positively associated with several common cancers, evidence regarding their association with brain tumor risk remains sparse, particularly in Asian populations. In this study, we analyzed the association between height and BMI and brain tumor risk in a Japanese population using a large population-based prospective cohort study.Methods: A total of 102,925 participants (48,213 men and 54,712 women) enrolled in the Japan Public Health Center-based Prospective Study were followed from baseline, namely 1990 for cohort I and 1993 for cohort II, until 2012. Information on participants' dietary and lifestyle habits, including height and body weight, was collected through survey questionnaires administered at baseline. We used the Cox proportional hazards regression model to estimate hazard ratios and 95% confidence intervals (CIs) for brain tumor incidence, with adjustment for potential confounding variables.Results: During an average follow-up of 18.1 years, 157 (70 men and 87 women) cases of brain tumor were newly diagnosed. BMI showed a statistically insignificant positive association with the risk of brain tumor. In addition, statistically significant positive trends were seen for men and meningioma, with multivariable-adjusted hazard ratios for a BMI of 27.5 to less than 40 versus 18.5 to less than 23 kg per m2 of 2.14 (95% CI = 0.99-4.59) (P = 0.03) and 1.98 (95% CI = 0.84-4.67) (P = 0.046), respectively. In contrast, height showed no clear association with brain tumor risk, overall or in subgroup analysis.Conclusions: Compared with a BMI of 18 to less than 23.5 kg per m2, a higher BMI was associated with higher risk of brain tumor, particularly in men and with meningioma. [ABSTRACT FROM AUTHOR]

Somatic base substitution mutations of frequencies at the 10-6/bp level are expected to be present in many biomedical samples, such as tissues exposed to carcinogenic factors and exhausted stem cells. However, measurement of such rare mutations has been very difficult in human DNA samples. Here, we invented the use of 100 copies of genomic DNA as a template for amplicon deep sequencing so that a real mutation in a single DNA molecule would be detected at a variant allele frequency of 1% while sequencing errors have less frequency. In addition, we selected 15,552 error-resistant base positions whose mutation frequency was expected to reflect that of base positions that can drive carcinogenesis or potentially even of the entire genome. The validity of the method was first confirmed by the successful detection of mutations premixed at the frequency of 0.1%. Second, increasing mutation frequencies (4-60 × 10-6/bp) were successfully detected in cells treated with increasing doses of one of two mutagens, and their signature mutations were detected. The ratio of non-synonymous mutations to synonymous mutations time-dependently decreased after treatment with a mutagen, supporting the neutral theory of molecular evolution for somatic mutations. Importantly, gastric mucosae exposed to Helicobacter pylori infection was shown to have significantly higher mutation frequency than those without. These results demonstrated that our new method can be used to measure rare base substitution mutations at the 10-6/bp level, and is now ready for a wide range of applications. [ABSTRACT FROM AUTHOR]

Background: Psychological stress is a modifiable risk factor for health outcomes and can be managed through coping mechanisms. Biological and behavioral hypotheses have been proposed to explain the association between stress coping strategies and cancer outcomes.Methods: The Japan Public Health Center-based study asked questions on coping behaviors in its 10-year follow-up survey. 55,130 subjects aged 50-79 without a history of cancer diagnosis and who provided complete answers on coping were included in analyses on cancer incidence and mortality. Hazard Ratios (HR) according to coping style were determined using Cox regression models adjusted for known confounders for cancer.Results: Mean follow-up time was 9.5 years for cancer incidence and 9.8 years for cancer mortality. The utilization of the approach-oriented coping strategy (HR=0.85, 95% CI: 0.72-0.99) and a behavior of positive reappraisal (HR=0.84, 95% CI: 0.72-0.97) was associated with a reduced risk of cancer mortality. The approach-oriented coping strategy was further associated with localized cancer incidence (HR=1.13, 95% CI: 1.01-1.27) and screening-detected cancers (HR=1.35, 95% CI: 1.15-1.58). The avoidance oriented coping strategy was inversely associated with cancer incidence (HR=0.69, 95% CI: 0.50-0.94) only after excluding events occurring in the first three years of follow-up.Conclusion: The results of this study may favor the behavioral hypothesis to explain associations between premorbid coping styles and cancer outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Cross-sectional studies have shown an association between different coping styles and suicidal behavior. It is unknown whether there is any prospective association between coping behaviors and suicide in the general population. Methods: The study population consisted of participants of the Japanese Public Health Center-based Prospective Study. In the 10-year follow-up questionnaire, subjects aged 50–79 years were asked how they handle daily problems. Coping behaviors were used to determine two coping strategies (approach coping and avoidance coping). Of 99,439 subjects that returned the 10-year follow-up questionnaire, 70,213 subjects provided complete answers on coping and were included in our analyses. Cox regression models, adjusted for confounders, were used to determine the risk of committing suicide according to coping style. Mean follow-up time was 8.8 years. Results: Two coping behaviors were significantly associated with suicide over time: planning (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.41–0.98) and self-blame (HR, 2.20; 95% CI, 1.29–3.76). Of the coping strategies, only the avoidance coping strategy was significantly associated with suicide (HR, 2.45; 95% CI, 1.24–4.85). Conclusions: For the first time, two coping behaviors and one coping strategy have been shown to have a significant prospective association with suicide in a general population. [Copyright &y& Elsevier]

Purpose: Although obesity is a risk factor for kidney cancer, few reports have investigated this association in Asian populations, notwithstanding the substantially different proportion of obesity between Asian and Western populations. Herein, we investigate the association between body mass index (BMI) and kidney cancer risk in Japanese persons, a relatively lean population. Methods: The Japan Public Health Center–based Prospective Study was established in 1990 for Cohort I and in 1993 for Cohort II. Subjects in this study were 46,837 men and 52,625 women, 40–69 years of age, who answered a questionnaire at baseline and were followed up until the end of 2006. During this time, 101 men and 38 women were newly diagnosed with kidney cancer. Results: In men, a U-shaped association between BMI and kidney cancer risk was observed, with a BMI of 23.0–24.9 showing the lowest risk (23–24.9: reference; <21: hazard ratio [HR] = 1.86; 95% confidence interval [CI] = 1.01–3.45, ≥27: HR = 1.99, 95% CI = 1.04–3.81). In women, the association was not clear because of the small number of cases, but high BMI was insignificantly associated with an increased risk of kidney cancer (21–24.9: reference; ≥25: HR = 1.55, 95% CI = 0.76–3.18). Conclusions: Not only high but also low BMI may increase risk of kidney cancer in populations with low average BMI. [Copyright &y& Elsevier]

Abstract: Objective: Obesity is an increasingly prevalent public health problem worldwide, and is associated with a higher risk of developing various noncommunicable diseases. To further examine the association between personality and overweight, obesity, or underweight, we conducted a cross-sectional analysis in Japan. We hypothesized that extraversion and psychoticism would have a positive association with overweight, and that neuroticism and lie would have an inverse association with overweight, whereas the association between personality and underweight would be the reverse image of overweight. Methods: In 1990, 30,722 subjects (40–64 years of age) completed a self-administered questionnaire including body weight and height and the Japanese version of the Eysenck Personality Questionnaire-Revised Short Form. Multivariate logistic regression analysis was used to calculate odds ratios for overweight [body mass index (BMI)≥25.0 kg/m2] or underweight (BMI<18.5) relative to each category on the personality subscale. Results: In men and women, extraversion and psychoticism had positive associations with overweight, whereas neuroticism had an inverse association. Lie had an inverse association with overweight in men. In men and women, only extraversion had an inverse association with underweight and neuroticism had a positive association with underweight. Conclusion: Our findings indicate that personality is associated with both overweight and underweight. These results may provide clues to devising more effective measures for preventing overweight, obesity, or underweight or for weight control intervention. [Copyright &y& Elsevier]

Abstract: The association between alcohol consumption and the risk of cancer of the proximal or distal colon or rectum remains controversial. We examined this association in a large population-based cohort of Japanese men. In 1990, a self-administered questionnaire on alcohol drinking and other health habits was delivered to 25,279 Japanese men aged 40 to 64 years of age. After exclusion of subjects who gave incomplete responses on alcohol drinking or prevalent cancer cases at the baseline, a total of 21,199 men remained. Of these, 307 men were diagnosed as having colorectal cancer after 11 years of follow-up. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with adjustments made for potential confounders. Compared with never drinkers, past and current drinkers had multivariate HRs of 1.1 (95% CI, 0.6–1.9) and 1.6 (95% CI, 1.1–2.2) for colorectal cancer, respectively. A dose-response relationship with current volume of alcohol drinkers was observed for cancer of the distal colon and rectum, but not for proximal colon. The multivariate HRs for distal colon and rectal cancer among current heavy drinkers (45.6 g or more ethanol per day) as compared with never drinkers were 4.2 (1.6–10.7; p for trend = 0.0002) and 1.8 (1.1–3.2; p for trend = 0.04), respectively. In contrast, no significant linear association was found for proximal colon cancer (p for trend = 0.2). These data indicate that alcohol consumption in Japanese men is associated with a statistically significant increased risk of cancer of the distal colon and rectum, but not cancer of the proximal colon. [Copyright &y& Elsevier]

Abstract: Objective: The aim of this study is to examine the association between obesity and depressive symptoms in Japan. Methods: We conducted a cross-sectional study of 1128 community-dwelling elderly Japanese aged 70 years or older in 2002. We calculated the body mass index [BMI=weight (kg)/height (m)2] from measured weight and height and evaluated depressive symptoms using the 30-item Geriatric Depression Scale (GDS 30), with a cut-off point of 11. Results: In men, no apparent association was observed between BMI and depressive symptoms. An inverse linear trend was observed in women overall, but stratified analysis of chronic medical conditions, such as stroke or cancer, showed an inverse association was evident only among women with the conditions. Among women without these chronic conditions, no apparent association was evident. Conclusion: No apparent association was observed in men overall or in apparently healthy women. An inverse trend was observed only in women with chronic medical conditions. [Copyright &y& Elsevier]

Purpose: We investigated the association between reproductive history and mortality from all and major causes among Japanese women.Methods: A large-scale population-based cohort study in Japan included 40,149 eligible women aged 40-69 years in 1990-1994. A total of 4788 deaths were reported during follow-up (average 20.9 years). A Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CI) for all-cause and major causes of mortality, adjusting for potential confounders.Results: Inverse associations with all-cause mortality were found in parous women (0.74 [0.67-0.82]), women with two or three births compared with a single birth (2 births: 0.88 [0.78-0.99]; 3 births: 0.83 [0.74-0.94]), parous women who breastfed (0.81 [0.75-0.87]), women who were older at menopause (0.88 [0.80-0.97]; p-trend: <0.01), and women who had a longer fertility span (0.85 [0.76-0.95]; p-trend: <0.01). A positive association was seen between all-cause mortality and later age at first birth (≥30 years) than early childbearing (≤22 years).Conclusions: Our study suggests that parous, two or three births, breastfeeding, late age at menopause, and longer reproductive span are associated with lower risk of all-cause of mortality. [ABSTRACT FROM AUTHOR]