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To deal with the risk of emerging diseases with many unknowns, close and timely collaboration and communication between science experts and policymakers are crucial to developing and implementing an effective science-based intervention strategy. The Expert Meeting, an ad hoc medical advisory body, was established in February 2020 to advise Japan's COVID-19 Response Headquarters. The group played an important role in the policymaking process, promoting timely situation awareness and developing science-based proposals on interventions that were promptly reflected in government actions. However, this expert group may have been overly proactive in taking on the government's role in crisis management. For the next stage of managing the coronavirus disease pandemic and future pandemics, the respective roles of the government and its advisory bodies need to be clearly defined. Leadership and strategic risk communication by the government are key.

The involvement of patients and the public with researchers is essential in clinical research on cancer treatment. In recent years, patient and public involvement(PPI)has been required in all medical research processes. This paper summarizes practical considerations and examples of the PPI process referred to in the"Patient and Public Involvement(PPI)Guidebook"of the Japan Agency for Medical Research and Development(AMED). The process consists of the introduction of PPI, recruitment of PPI participants, conflict of interest management and rewards for PPI participants, the confidentiality of PPI participants, and reporting results and feedback. It is difficult to provide a standardized procedure because PPI activities vary among the research projects. It is recommended to implement PPI activities into your research project by utilizing the actual cases or existing information sources.

Since the 1990s, insurance has been the primary field focused on the social disadvantages of using genetic test results because of the concerns related to adverse selection. Although life insurance is popular in Japan, Japan does not currently have any regulations on the use of genetic information and insurers have largely kept silent for decades. To reveal insurers’ attitudes on the topic, we conducted an anonymous questionnaire survey with 100 insurance company employees and recruited nine interviewees from the survey respondents. We found that genetic discrimination is not generally considered as a topic of human rights. We also found that insurers have uncertain fears and concerns about adverse selection in terms of actuarial fairness but not regarding profits. When it comes to preparing guidelines on the use of genetic information by Japanese insurers, we believe that public dialog and consultation are necessary to gain understanding of the people.

Background The burden of dementia is growing rapidly and has become a medical and social problem in Japan. Prospective cohort studies have been considered an effective methodology to clarify the risk factors and the etiology of dementia. We aimed to perform a large-scale dementia cohort study to elucidate environmental and genetic risk factors for dementia, as well as their interaction. Methods The Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) is a multisite, population-based prospective cohort study of dementia, which was designed to enroll approximately 10,000 community-dwelling residents aged 65 years or older from 8 sites in Japan and to follow them up prospectively for at least 5 years. Baseline exposure data, including lifestyles, medical information, diets, physical activities, blood pressure, cognitive function, blood test, brain magnetic resonance imaging (MRI), and DNA samples, were collected with a pre-specified protocol and standardized measurement methods. The primary outcome was the development of dementia and its subtypes. The diagnosis of dementia was adjudicated by an endpoint adjudication committee using standard criteria and clinical information according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Revised Edition. For brain MRI, three-dimensional acquisition of T1-weighted images was performed. Individual participant data were pooled for data analyses. Results The baseline survey was conducted from 2016 to 2018. The follow-up surveys are ongoing. A total of 11,410 individuals aged 65 years or older participated in the study. The mean age was 74.4 years, and 41.9% were male. The prevalence of dementia at baseline was 8.5% in overall participants. However, it was 16.4% among three sites where additional home visit and/or nursing home visit surveys were performed. Approximately two-thirds of dementia cases at baseline were Alzheimer’s disease. Conclusions The prospective cohort data from the JPSC-AD will provide valuable insights regarding the risk factors and etiology of dementia as well as for the development of predictive models and diagnostic markers for the future onset of dementia. The findings of this study will improve our understanding of dementia and provide helpful information to establish effective preventive strategies for dementia in Japan.

Genome editing of human embryos could become a fundamental treatment approach for genetic diseases; however, a few technical and ethical issues need to be resolved before its application in clinical settings. Presently, the Japanese government has issued a statement prohibiting human germline editing and emphasizing the need for discussions that include a wide range of perspectives. However, current discussions tend to exclude the general public. Therefore, we conducted a survey of 10,881 general adults and 1044 patients in Japan who indicated that their disease conditions are related to their genetic makeup, and clarified their attitude toward this technology. The results clearly indicated that the Japanese people generally accepted the use of genome editing for disease-related genes, but many were concerned about the risks. In addition, many Japanese people did not understand the technology well. To improve awareness and understanding about genome editing, it is important that scientists and science communicators create opportunities for the public to participate in relevant discussions without harming vulnerable participants. It is also important to continuously track changes in the acceptance of genome editing by the public.

Introduction One of the ethical issues surrounding birth cohort studies is how to obtain informed assent from children as they grow up. What and how parents tell their children affects children's future choices about the study, yet few studies have focused on parents’ influence on children. Objective This study examines parents’ attitudes towards telling their children about their participation in a specific birth cohort study. Methods We conducted surveys and in‐depth interviews with the parents of children who participated in the “Japan Environment and Children's Study” (JECS), which follows children from the foetal stage to age 13. Results Forty‐four mothers and 23 fathers answered the survey, and 11 mothers and 3 fathers participated in in‐depth interviews. Parents’ attitudes towards “telling” were categorized into 3 communication styles depending on their perception of the risk/benefits for their children. Most parents predicted that the study would benefit their children and preferred “directive telling,” which we divided into “empowered telling” (provides children with a positive identity as participants) and “persuasive telling” (attempts to persuade children even if they express reluctance as they grow). A few parents, weighing the study's potential risk, preferred “non‐directive telling,” which respects children's choices even if that means withdrawing from the study. Discussion While “directive telling” may lead children to have positive associations with the study, children should also be told about the risks. Investigators can provide materials that support parents and give children age‐appropriate information about their participation, as well as ensure opportunities for children to express their feelings.

BackgroundLeftover samples obtained during autopsies are extremely important basic materials for forensic research. However, there are no established practices for research-related use of obtained samples.ObjectiveThis study discusses good practice for the secondary use of samples collected during medicolegal autopsies.MethodsA questionnaire was posted to all 76 departments of forensic medicine performing medicolegal autopsies in Japan, and 48 responses were received (response rate: 63.2%). As a secondary analysis, we surveyed information provided on department websites.ResultsEthical reviews conducted when samples were to be used for research varied greatly among departments, with 21 (43.8%) departments reporting ‘fundamentally, all cases are subject to review’, eight (16.7%) reporting ‘only some are subject to review’ and 17 (39.6%) reporting ‘none are subject to review’. Information made available on websites indicated that 11 departments had a statement of some type to bereaved families about the potential research use of human samples obtained during autopsies. Nine of these included a notice stating that bereaved families may revoke their consent for use. Several departments used an opt-out system.ConclusionThere is no common practice in the field of legal medicine on the ethical use for medical research of leftover samples from medicolegal autopsies. The trust of not only bereaved families but also society in general is required for the scientific validity and social benefits of medical studies using leftover samples from medicolegal autopsies through the use of opt-out consenting and offline and online dissemination and public-relations activities.

The Japanese government instituted countermeasures against COVID-19, a pneumonia caused by the new coronavirus, in January 2020. Seeking "people's behavioral changes," in which the government called on the public to take precautionary measures or exercise self-restraint, was one of the important strategies. The purpose of this study is to investigate how and from when Japanese citizens have changed their precautionary behavior under circumstances in which the government has only requested their cooperation. This study uses micro data from a cross-sectional survey conducted on an online platform of an online research company, based on quota sampling that is representative of the Japanese population. By the end of March 2020, a total of 11,342 respondents, aged from 20 to 64 years, were recruited. About 85 percent reported practising the social distancing measures recommended by the government including more females than males and more older than younger participants. Frequent handwashing is conducted by 86 percent of all participants, 92 percent of female, and 87.9 percent of over-40 participants. The most important event influencing these precautionary actions was the infection aboard the Diamond Princess cruise ship, which occurred in early February 2020 (23 percent). Information from the central and local governments, received by 60 percent of the participants, was deemed trustworthy by 50 percent. However, the results also showed that about 20 percent of the participants were reluctant to implement proper prevention measures. The statistical analysis indicated that the typical characteristics of those people were male, younger (under 30 years old), unmarried, from lower-income households, a drinking or smoking habit, and a higher extraversion score. To prevent the spread of infection in Japan, it is imperative to address these individuals and encourage their behavioural changes using various means to reach and influence them.

Background Prostate cancer is the sixth leading cause of cancer-related deaths in Japan. We aimed to elucidate the clinical and histopathological characteristics of patients with prostate cancer in the BioBank Japan (BBJ) project. Methods Four thousand, seven hundred and ninety-three patients diagnosed with prostate cancer in the BBJ project were included. Clinical and histopathological data, including causes of death, were analyzed. Relative survival (RS) rates of prostate cancer were calculated. Results Four thousand, one hundred and seventy-one prostate cancer patients with available histological data had adenocarcinoma. The mean age of the patients was 72.5 years. The proportion of patients who were non-smokers, non-drinkers, had a normal body mass index, did not exercise, had a normal prostate-specific antigen level, and had a family history of prostate cancer were 30.7%, 28.0%, 66.6%, 58.1%, 67.6%, and 6.5%, respectively. The proportion of patients with Stage II, III, and IV disease were 24.4%, 7.3%, and 4.4%, respectively. After limiting to patients with a time from the initial diagnosis of prostate cancer to entry into the study cohort of ≤90 days (n = 869), the 5- and 10-year RS rates were 96.3% and 100.5%, respectively, although we were unable to consider management strategies due to a plenty of data missing. Conclusions We provide an overview of patients with prostate cancer in the BBJ project. Our findings, coupled with those from various high throughput “omics” technologies, will contribute to the implementation of prevention interventions and medical management of prostate cancer patients., Highlights • Prostate cancer represents the second leading cause of cancer incidence worldwide. • We aimed to provide an overview of patients with prostate cancer. • Based on prostate cancer histology, 99.3% had adenocarcinoma. • The 5- and 10-year relative survival rates were 96.3% and 100.5%. • Future studies will help develop preventive programs for prostate cancer.

Background Liver cancer is the fifth cause of cancer-related deaths in Japan. The BioBank Japan (BBJ) project included 200,000 patients with 47 diseases and samples; their clinical information can be used for further studies. Methods Patients diagnosed with liver cancer (n = 1733; 1316 men, 417 women) were included. Histology, patient characteristics, clinical characteristics, and causes of death were collected. Cumulative and relative survival rates for liver cancer were calculated. Results Of the 1354 patients with available liver cancer histology, 91.9% had hepatocellular carcinoma (HCC). Compared with the National Health and Nutrition Examination Survey, greater proportions of the male patients in this cohort were daily alcohol consumers (26%), and a greater proportion of the men was overweight/obesity (22%). Although Japan is the only Asian country with a predominance of hepatitis C virus (HCV)-related HCC, the prevalence of HCV infection (44%) was lower than that in a previous study. The 3-, 5-, and 10-year cumulative survival rates were 57%, 47%, and 25% in men, respectively, and 49%, 41%, and 27% in women, respectively. Conclusions The present results provide an overview of the patients with liver cancer in the BBJ project. We are planning further analyses combined with various high-throughput ‘omics’ technologies., Highlights • Liver cancer is the second leading cause of death worldwide. • We aimed to provide an overview of patients with liver cancer. • Based on liver cancer histology, 91.9% had hepatocellular carcinoma. • The 10-year relative survival rates were 34% in men and 38% in women. • Future studies will help develop preventive programs for liver cancer.

Background Breast cancer is currently the most common type of cancer in Japanese females. Unlike most other types of cancer, breast cancer develops more frequently in middle-aged females than in elderly females. Methods Of all Japanese female breast cancer patients aged ≥20 years whom the BioBank Japan Project originally enrolled between 2003 and 2008, 2034 were registered within 90 days after their diagnosis. We described the lifestyle and clinical characteristics of these patients at study entry. Furthermore, we examined the effect of these characteristics on all-cause mortality. Results In the female patients registered within 90 days after diagnosis, the frequency of stage 0 or unclassified, stage I, II, III and IV were 11.4%, 47.9%, 37.0%, 2.9% and 0.8%, respectively. The proportion of histological types was 12.9% for non-invasive carcinoma (ductal carcinoma and lobular carcinoma), 81.0% for invasive carcinoma (papillotubular carcinoma, solid tubular carcinoma, scirrhous carcinoma and special types), 0.2% for Paget's diseases and 5.8% for others. Those positive for the estrogen and progesterone receptors accounted for 75.8% and 62.1% of all patients, respectively. Among 1860 female participants registered within 90 days, 218 participants died during 144,54 person-years of follow-up. More advanced stage, elevation of serum carcinoembryonic antigen and carbohydrate antigen 15-3 levels and absence of the estrogen receptor at study entry were crudely associated with an increased risk of all-cause mortality after adjustment for age. Conclusions This study showed the association of several clinical characteristics with all-cause mortality in female breast cancer patients., Highlights • About 1% of Japanese female breast cancer patients were diagnosed as stage IV. • Invasive carcinoma was much more common than non-invasive carcinoma. • Papillotubular carcinoma was the most common type of invasive carcinoma. • About 75% were positive for estrogen receptor and 60% for progesterone receptor. • Some characteristics would affect all-cause mortality in breast cancer patients.

Background Colorectal cancer is the third most common cancer worldwide, and in Japan, it is estimated that about 10% of men and 8% of women will be diagnosed with colorectal cancer during their lifetime. Methods We focused on 5864 participants (3699 men and 2165 women) who had colorectal cancer and were registered with BioBank Japan (BBJ) between April 2003 and March 2008. Characteristics of colon and rectal cancer patients were calculated separately. Among the enrolled patients registered in BBJ within 90 days after diagnosis, we also calculated the 5-year cumulative and relative survival rates, and estimated the effect of lifestyle factors on all-cause mortality. Results Our participants included younger men than those in the Patient Survey and the Cancer Registry Japan. In more than 95% of cases the histological type was adenocarcinoma both in colon and rectal cancer. Rectal cancer patients tended to eat more meat and less green leafy vegetables compared with colon cancer patients. The 5-year cumulative survival rate was 73.0% (95% CI; 70.1%–75.7%) and the 5-year relative survival rate was 80.6% (77.4%–83.6%), respectively, for colon cancer. For rectal cancer, the rates were 73.3% (69.1%–77.0%) and 80.9% (76.3%–85.0%), in the same order. Lifestyle factors such as consuming less green leafy vegetables, being underweight, smoking, not consuming alcoholic beverages and being physically inactive were found to be related to poor survival. Conclusions We described lifestyle characteristics of colorectal cancer patients in BBJ and examined the impacts on subsequent all-cause mortality., Highlights • More than 95% were adenocarcinoma both in colon and rectal cancer. • Rectal cancer patients ate more meat and less green vegetables than colon cancer. • Eating green vegetables and drinking alcohol moderately decreased the mortality risk.

Background The number of patients with diabetes is increasing worldwide. Macrovascular disease, chronic kidney disease, chronic respiratory disease, cancer and smoking frequently accompany type 2 diabetes. Few data are available related to mortality of Asians with diabetes associated with these serious comorbidities. The present study aimed to quantify the excess mortality risks of type 2 diabetic patients with comorbidities. Methods We analysed the available records of 30,834 Japanese patients with type 2 diabetes from the BioBank Japan Project between 2003 and 2007. Men and women were followed up for median 8.03 and 8.30 years, respectively. We applied Cox proportional hazard model and Kaplan–Meier estimates for survival curves to evaluate mortality in diabetic patients with or without macrovascular disease, chronic respiratory disease, chronic kidney disease, cancer and smoking. Results Adjusted hazard ratios (HRs) for mortality were 1.39 (95% CI, 1.09–1.78) for male sex, 2.01 (95% CI, 1.78–2.26) per 10-year increment of age. Adjusted HRs of primary interest were 1.77 (95% CI, 1.42–2.22), macrovascular disease; 1.58 (95% CI, 1.08–2.31), chronic respiratory disease; 2.03 (95% CI, 1.67–2.47), chronic kidney disease; 1.16 (95% CI, 0.86–1.56), cancer; and 1.74 (95% CI, 1.30–2.31), current smoking. Conclusions Diabetic patients with a past or current history of chronic kidney, macrovascular or respiratory diseases or smoking habit have exhibited the highest risk of mortality. Data were limited to those of survivors of comorbidities but we propose the need to improve comorbidities and terminate cigarette smoking for better prognosis in patients with diabetes., Highlights • Fatal diseases frequently accompany diabetes. • Data for survival of Asian patients with diabetes with comorbidities are scarce. • Comorbid chronic kidney disease was associated with the most fatalities. • Current smoking was as fatal as 10 years of ageing in diabetic patients. • Values of 1% HbA1c and 10 mmHg blood pressure confer 11% excess mortality risk.

Background Controlling serum cholesterol is critical to prevent cardiovascular disease in patients with dyslipidaemia. Guidelines emphasise the need to select treatment for dyslipidaemia based on specific patient profiles; however, there is little information about the serum cholesterol levels of patients in each profile in Japan. Therefore, we aimed to describe the serum cholesterol levels and prevalence of uncontrolled cases in Japanese patients with dyslipidaemia. Methods We included data for patients with dyslipidaemia between 2003 and 2007 from the BioBank Japan Project (66 hospitals). Then, we reported their serum cholesterol levels by age, body mass index, glycaemic control (glycated haemoglobin A1c), blood pressure, smoking, drinking, comorbidity and medication profiles. Results We included 22,189 male and 21,545 female patients. The mean serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG) and non-HDL-C levels in males were 117.4 mg/dL, 51.0 mg/dL, 187.6 mg/dL and 153.6 mg/dL, respectively; the corresponding levels in females were 129.5 mg/dL, 60.5 mg/dL, 144.9 mg/dL and 157.9 mg/dL, respectively. In both males and females, the LDL-C levels were the highest in the following profiles: age 19–44 years, body mass index 18.5–22 kg/m2, glycated haemoglobin A1c, Highlights • Evidence of serum cholesterol control in Japanese dyslipidaemic patients is scarce. • We analysed data for a large-scale population in hospital settings. • Our findings provide serum cholesterol levels by different risk profiles. • Serum lipid levels were the lowest in the youngest patients. • Data should be carefully applied to patients with mild hyperlipidaemia.

Owing to the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic worldwide, individuals experience considerable psychological distress daily. The present study aimed to clarify the prevalence of psychological distress and determine the population most affected by risk factors such as the pandemic, socioeconomic status (SES), and lifestyle-related factors causing psychological distress in the early phases of the pandemic in Japan. This study was conducted via a web-based survey using quota sampling to ensure representativeness of the Japanese population aged 20–64 years. A cross-sectional study of 11,342 participants (5,734 males and 5,608 females) was conducted using a self-administered questionnaire that included the Japanese version of the Kessler 6 Psychological Distress Scale (K6) and questions related to the pandemic, SES, and lifestyle. The prevalence of psychological distress, represented by a K6 score of 5 or more, was 50.3% among males and 52.6% among females. Both males and females with annual household incomes less than 2 million yen and males aged in their twenties had significantly higher K6 scores than those with annual household incomes above 2 million yen and males aged over 30 years. Binary logistic regression analyses found pandemic-related factors such as medical history, inability to undergo clinical tests immediately, having trouble in daily life, unavailability of groceries, new work style, and vague anxiety; SES-related factors such as lesser income; and lifestyle-related factors such as insufficient rest, sleep, and nutritious meals to be significantly related to psychological distress. Psychological distress was more prevalent among people with low income and in younger generations than among other groups. There is an urgent need to provide financial, medical, and social support to those affected by the coronavirus disease 2019 (COVID-19) pandemic.

Background Platforms for sharing genomic and phenotype data have been developed to promote genomic research, while maximizing the utility of existing datasets and minimizing the burden on participants. The value of genomic analysis of trios or family members has increased, especially in rare diseases and cancers. This article aims to argue the necessity of protection when sharing data from both patients and family members. Main text Sharing patients’ and family members’ data collectively raises an ethical tension between the value of datasets and the rights of participants, and increases the risk of re-identification. However, current data-sharing policies have no specific safeguards or provisions for familial data sharing. A quantitative survey conducted on 10,881 general adults in Japan indicated that they expected stronger protection mechanisms when their family members’ clinical and/or genomic data were shared together, as compared to when only their data were shared. A framework that respects decision-making and the right of withdrawal of participants, including family members, along with ensuring usefulness and security of data is needed. To enable this, we propose recommendations on ancillary safeguards for familial data sharing according to the stakeholders, namely, initial researchers, genomic researchers, data submitters, database operators, institutional review boards, and the public and participants. Conclusions Families have played significant roles in genetic research, and its value is re-illuminated in the era of genomic medicine. It is important to make progress in data sharing while simultaneously protecting the privacy and interests of patients and families, and return its benefits to them.

Objectives This study examines the dissemination of Honnintsuchiseido (a system of providing notifications to citizens that a municipality issued a copy of resident record to a third party) in Japan and its effect on the use of copies of resident record for academic research.Methods In February and March 2015, a telephone survey was conducted in 1,741 municipalities (including special wards) in Japan. The survey examined the implementation of Honnintsuchiseido and standards for issuing copies of resident record for academic research in the municipalities. Further, we analyzed the implementation of Honnintsuchiseido and the results of requests for issuing copies of resident record for the Biobank Japan (BBJ) project.Results The results found that 28.9% of the municipalities had already introduced Honnintsuchiseido. Approximately 85% of the municipalities responded that their each official judged the issuance of copies of resident record for academic research based on a handbook of paperwork for the Basic Resident Registration. Further, approximately 14% responded that they had common definite standards in their officials for judging the issuance of copies of resident record for academic research. One of the main reasons for the refusal to issue copies of resident record in the BBJ project was that the consent form of the project did not specify the use of the resident record. In addition, some municipalities refused because the standards for judgments were revised with the implementation of Honnintsuchiseido. However, there was no significant association between the introduction of Honnintsuchiseido and the refusal to issue copies of resident record for the BBJ project.Conclusions Some municipalities refused to issue copies of resident record because the standards were revised with the implementation of Honnintsuchiseido. Further, many municipalities did not have any common specific criteria for judging the issuance of copies of resident record for academic purposes. Therefore, specific standards should be formulated to clarify the type of research having public interest, which will support the judgment of municipalities regarding the issuance of copies of resident record for academic research.

Background We established a patient-oriented biobank, BioBank Japan, with information on approximately 200,000 patients, suffering from any of 47 common diseases. This follow-up survey focused on 32 diseases, potentially associated with poor vital prognosis, and collected patient survival information, including cause of death. We performed a survival analysis for all subjects to get an overview of BioBank Japan follow-up data. Methods A total of 141,612 participants were included. The survival data were last updated in 2014. Kaplan–Meier survival analysis was performed after categorizing subjects according to sex, age group, and disease status. Relative survival rates were estimated using a survival-rate table of the Japanese general population. Results Of 141,612 subjects (56.48% male) with 1,087,434 person-years and a 97.0% follow-up rate, 35,482 patients died during follow-up. Mean age at enrollment was 64.24 years for male subjects and 63.98 years for female subjects. The 5-year and 10-year relative survival rates for all subjects were 0.944 and 0.911, respectively, with a median follow-up duration of 8.40 years. Patients with pancreatic cancer had the least favorable prognosis (10-year relative survival: 0.184) and patients with dyslipidemia had the most favorable prognosis (1.013). The most common cause of death was malignant neoplasms. A number of subjects died from diseases other than their registered disease(s). Conclusions This is the first report to perform follow-up survival analysis across various common diseases. Further studies should use detailed clinical and genomic information to identify predictors of mortality in patients with common diseases, contributing to the implementation of personalized medicine., Highlights • 141,612 participants with any of 32 diseases were included in the follow-up survey. • Subject characteristics at enrollment for the follow-up survey were identified. • The relative survival analysis showed the worst prognosis in pancreatic cancer. • The most common cause of death in all subjects was malignant neoplasms.

Background Evidence of characteristics of Japanese patients with diabetes from a large-scale population is necessary. Few studies have compared glycaemic controls, complications and comorbidities between type 1 and 2 diabetic patients. This paper focuses on illustrating a clinical picture of Japanese diabetic patients and comparing glycaemic control and prognoses between type 1 and 2 diabetes using multi-institutional data. Methods The BioBank Japan Project enrolled adult type 1 and 2 diabetic patients between fiscal years 2003 and 2007. We have presented characteristics, controls of serum glucose, cholesterol and blood pressure, prevalence of complications and comorbidities and survival curves. We have also shown glycaemic controls according to various individual profiles of diabetic patients. Results A total of 558 type 1 diabetic patients and 30,834 type 2 diabetic patients participated in this study. The mean glycated haemoglobin A1c was higher in type 1 diabetes than in type 2 diabetes. In the type 1 diabetic patients, the glycated haemoglobin A1c had no consistent trend according to age and body mass index. The Kaplan–Meier estimates represented a longer survival time from baseline with type 1 diabetes than with type 2 diabetes. Compared with type 1 diabetic patients, type 2 diabetic patients had double the prevalence of macrovascular complications. Conclusions This work has revealed detailed plasma glucose levels of type 1 and 2 diabetic patients according to age, body mass index, blood pressure, serum cholesterol levels and smoking and drinking habits. Our data have also shown that the prognosis is worse for type 2 diabetes than for type 1 diabetes in Japan., Highlights • Detailed glycaemic control data of diabetic patients are necessary. • Few studies have compared the survival times between type 1 and 2 diabetes. • Higher glycated HbA1c was observed in type 1 than in type 2 diabetes. • Data showed higher hazard ratio of mortality in type 1 than in type 2 diabetes. • Fewer macrovascular complications accompany type 1 than type 2 diabetes.

Background To implement personalized medicine, we established a large-scale patient cohort, BioBank Japan, in 2003. BioBank Japan contains DNA, serum, and clinical information derived from approximately 200,000 patients with 47 diseases. Serum and clinical information were collected annually until 2012. Methods We analyzed clinical information of participants at enrollment, including age, sex, body mass index, hypertension, and smoking and drinking status, across 47 diseases, and compared the results with the Japanese database on Patient Survey and National Health and Nutrition Survey. We conducted multivariate logistic regression analysis, adjusting for sex and age, to assess the association between family history and disease development. Results Distribution of age at enrollment reflected the typical age of disease onset. Analysis of the clinical information revealed strong associations between smoking and chronic obstructive pulmonary disease, drinking and esophageal cancer, high body mass index and metabolic disease, and hypertension and cardiovascular disease. Logistic regression analysis showed that individuals with a family history of keloid exhibited a higher odds ratio than those without a family history, highlighting the strong impact of host genetic factor(s) on disease onset. Conclusions Cross-sectional analysis of the clinical information of participants at enrollment revealed characteristics of the present cohort. Analysis of family history revealed the impact of host genetic factors on each disease. BioBank Japan, by publicly distributing DNA, serum, and clinical information, could be a fundamental infrastructure for the implementation of personalized medicine., Highlights • The BioBank Japan Project (BBJ) annually collected clinical information. • Analysis of the clinical information at enrollment characterized the BBJ cohort. • Analysis of family history revealed impacts of host genetic factors on the diseases.

Background Statins are the first-line agents used to treat patients with high serum low-density lipoprotein cholesterol levels, thus reducing the risk of death from arterial sclerotic cardiovascular disease; however, little is known about the effects of non-statin pharmacological interventions on mortality as well as about the potential protective effects of statin use against cancer death. This work aimed to compare all-cause and cancer mortality among patients with hyperlipidaemia who did and did not receive statin treatment. Methods Between 2003 and 2007 fiscal years, we recruited Japanese patients diagnosed with hyperlipidaemia from 66 hospitals. Patients in our cohort were followed up for a maximum of 12 years to observe the causes of death. Kaplan–Meier estimates from the baseline were used to compare the mortality of patients based on the administered medicine. All-cause mortality were compared among patients with/without administration of statins and other agents; any-organ and colorectal cancer mortality were compared between patients with/without administration of statins. Results Our cohort included 41,930 patients with mean ages of 64–66 years and mean body mass indices of 24–25 kg/m2. Patients who received statin monotherapy and were treated with lifestyle modification exhibited nearly identical survival curves, whereas statin use represented a non-significant but potentially protective effect against colorectal cancer-related mortality. The lowest mortality in this cohort was associated with resin monotherapy. Conclusions Mortality rate has been similar for patients treated with statin monotherapy and lifestyle modification. Statin monotherapy could potentially reduce any-organ- and colorectal cancer-related mortality., Highlights • Statin-mediated reduction of low-density lipoprotein levels reduces mortality. • Little is known on the effect of non-statin hyperlipidaemia medicines on mortality. • Statin monotherapy is safe in terms of cancer mortality. • Statin use may reduce colorectal cancer-related mortality. • Resin monotherapy was associated with the lowest mortality.

Background Several studies have evaluated associations between the characteristics of patients with esophageal and gastric cancer and survival, but these associations remain unclear. We described the distribution of demographic and lifestyle factors among patients with esophageal and gastric cancer in Japan, and investigated their potential effects on survival. Methods Between 2003 and 2007, 24- to 95-year-old Japanese patients with esophageal and gastric cancer were enrolled in the BioBank Japan Project. The analysis included 365 patients with esophageal squamous cell carcinoma (ESCC) and 1574 patients with gastric cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using medical institution-stratified Cox proportional hazards models. Results During follow-up, 213 patients with ESCC (median follow-up, 4.4 years) and 603 patients with gastric cancer (median follow-up, 6.1 years) died. Among patients with ESCC, the mortality risk was higher in ever drinkers versus never drinkers (multivariable HR = 2.37, 95% CI: 1.24, 4.53). Among patients with gastric cancer, the mortality risk was higher in underweight patients versus patients of normal weight (multivariable HR = 1.66, 95% CI: 1.34, 2.05). Compared to patients with gastric cancer with no physical exercise habit, those who exercised ≥3 times/week had a lower mortality risk (multivariate HR = 0.75, 95% CI = 0.61, 0.93). However, lack of stage in many cases was a limitation. Conclusions Among patients with ESCC, alcohol drinkers have a poor prognosis. Patients with gastric cancer who are underweight also have a poor prognosis, whereas patients with physical exercise habits have a good prognosis., Highlights • Among ESCC patients, alcohol drinkers had a poor prognosis. • Underweight gastric cancer patients had a poor prognosis. • Gastric cancer patients who exercised had a good prognosis. • No association between esophageal or gastric cancer and smoking was observed.

Background In Japanese males and females, lung cancer is currently the second and fourth most common type of cancer, and the first and second leading cause of cancer-related deaths, respectively. Methods Of all Japanese male and female lung cancer patients aged ≥20 years whom the BioBank Japan Project originally enrolled between 2003 and 2008, 764 males and 415 females were registered within 90 days after their diagnosis. We described the lifestyle and clinical characteristics of these patients at study entry. Furthermore, we examined the effect of these characteristics on all-cause mortality. Results In the lung cancer patients registered within 90 days, the frequencies of occult or stage 0, stage I, II, III and IV were 0.4%, 55.8%, 10.8%, 22.0% and 11.0% for males and 0.3%, 62.4%, 9.9%, 17.1% and 10.2% for females, respectively. The proportions of histological types in males and females were 56.3% and 82.4% for adenocarcinoma, 26.9% and 8.2% for squamous cell carcinoma, 4.5% and 1.5% for large cell carcinoma, 7.7% and 4.1% for small cell carcinoma and 4.6% and 3.8% for others, respectively. Among 1120 participants who registered within 90 days, 572 participants died during 5811 person-years of follow-up. Low body mass index, ever smoker, more advanced stage, squamous cell or small cell carcinoma and high serum carcinoembryonic antigen level at study entry were crudely associated with an increased risk of all-cause mortality after adjustment for age. Conclusions This study showed the association of several lifestyle and clinical characteristics with all-cause mortality in lung cancer patients., Highlights • Nearly one-tenth of Japanese lung cancer patients were diagnosed as stage IV. • Adenocarcinoma was the most common histological type in both males and females. • Some characteristics would affect all-cause mortality in lung cancer patients.

To clarify the attitude toward genetic testing for neuromuscular diseases, a questionnaire was sent to 4,762 neurologists certified by the Japanese Society of Neurology. By December 21, 2011, 1,493 questionnaires (31.4%) were returned. Of these, 1,233 (82.6%) had experienced genetic testing, but only 396 (26.5%) had referred to the guideline for genetic testing of the Japanese Society of Neurology (2009). The numbers of respondents who were positive, or more positive than negative for genetic testing for myotonic dystrophy type 1 (DM1), Huntington's disease (HD), and familial amyloid polyneuropathy (FAP) were 753 (50.4%), 915 (61.3%), and 980 (65.6%), respectively. The predominant reason for a positive attitude toward genetic testing was to confirm or exclude the diagnosis. Conversely, the predominant reason for a negative attitude toward genetic testing differed between the diseases. For DM1, it was to confirm the diagnosis without genetic testing. For HD, it was that genetic testing would not result in effective prevention or therapy. In FAP, it was that post-testing psychosocial support for the patient and their family was difficult. Common to DM1, HD, and FAP, a significant number of respondents (approximately 60%) felt it difficult to explain the negative aspects that might occur after the disclosure of test results. Concerning predictive or prenatal genetic testing, most respondents referred at-risk individuals to specialized genetic counseling clinics. In general, neurologists are likely to conduct genetic testing properly in consideration not only of the characteristics of the diseases but also of the circumstances of each patient and his or her family. To support neurologists who are involved in genetic testing, the guidelines should be more easily accessible. Many respondents wanted information on the institutions that provide genetic counseling and testing; however, financial support to such institutions is indispensable for fulfilling this requirement.

Background Cardiovascular disease (CVD) is a leading cause of death in Japan. The present study aimed to develop new risk prediction models for long-term risks of all-cause and cardiovascular death in patients with chronic phase CVD. Methods Among the subjects registered in the BioBank Japan database, 15,058 patients aged ≥40 years with chronic ischemic CVD (ischemic stroke or myocardial infarction) were divided randomly into a derivation cohort (n = 10,039) and validation cohort (n = 5019). These subjects were followed up for 8.55 years in median. Risk prediction models for all-cause and cardiovascular death were developed using the derivation cohort by Cox proportional hazards regression. Their prediction performances for 5-year risk of mortality were evaluated in the validation cohort. Results During the follow-up, all-cause and cardiovascular death events were observed in 2962 and 962 patients from the derivation cohort and 1536 and 481 from the validation cohort, respectively. Risk prediction models for all-cause and cardiovascular death were developed from the derivation cohort using ten traditional cardiovascular risk factors, namely, age, sex, CVD subtype, hypertension, diabetes, total cholesterol, body mass index, current smoking, current drinking, and physical activity. These models demonstrated modest discrimination (c-statistics, 0.703 for all-cause death; 0.685 for cardiovascular death) and good calibration (Hosmer-Lemeshow χ2-test, P = 0.17 and 0.15, respectively) in the validation cohort. Conclusions We developed and validated risk prediction models of all-cause and cardiovascular death for patients with chronic ischemic CVD. These models would be useful for estimating the long-term risk of mortality in chronic phase CVD., Highlights • We developed risk prediction models for death after cardiovascular disease (CVD). • Performances of these models were validated in an independent cohort. • Our models may be used to estimate mortality risk in chronic CVD patients.

Background The BioBank Japan (BBJ) Project was launched in 2003 with the aim of providing evidence for the implementation of personalized medicine by constructing a large, patient-based biobank (BBJ). This report describes the study design and profile of BBJ participants who were registered during the first 5-year period of the project. Methods The BBJ is a registry of patients diagnosed with any of 47 target common diseases. Patients were enrolled at 12 cooperative medical institutes all over Japan from June 2003 to March 2008. Clinical information was collected annually via interviews and medical record reviews until 2013. We collected DNA from all participants at baseline and collected annual serum samples until 2013. In addition, we followed patients who reported a history of 32 of the 47 target diseases to collect survival data, including cause of death. Results During the 5-year period, 200,000 participants were registered in the study. The total number of cases was 291,274 at baseline. Baseline data for 199,982 participants (53.1% male) were available for analysis. The average age at entry was 62.7 years for men and 61.5 years for women. Follow-up surveys were performed for participants with any of 32 diseases, and survival time data for 141,612 participants were available for analysis. Conclusions The BBJ Project has constructed the infrastructure for genomic research for various common diseases. This clinical information, coupled with genomic data, will provide important clues for the implementation of personalized medicine., Highlights • The BioBank Japan Project (BBJ) enrolled 200,000 patients with 47 target diseases. • The BBJ is one of the largest patient-based biobanks in the world. • The BBJ may allow for personalized medicine in the future.

This study aimed to assess public attitudes in Japan to the promotion of genomic selection in crop studies and to examine associated factors. We analysed data from a nationwide opinion survey. A total of 4,000 people were selected from the Japanese general population by a stratified two-phase sampling method, and 2,171 people participated by post; this survey asked about the pros and cons of crop-related genomic studies promotion, examined people’s scientific literacy in genomics, and investigated factors thought to be related to genomic literacy and attitude. The relationships were examined using logistic regression models stratified by gender. Survey results showed that 50.0% of respondents approved of the promotion of crop-related genomic studies, while 6.7% disapproved. No correlation was found between literacy and attitude towards promotion. Trust in experts, belief in science, an interest in genomic studies and willingness to purchase new products correlated with a positive attitude towards crop-related genomic studies.

Genomic tumor profiling tests (GTPTs) to find molecular targeted drugs for patients with advanced cancer are being introduced into clinical settings, which may result in secondary germline findings. Although small-scale qualitative studies have revealed patients' attitudes toward GTPTs and preferences on receiving germline findings, no large-scale quantitative research exists that includes family members. We conducted anonymous surveys with 757 cancer patients (CPs), 763 family members (FMs), and 3697 general adults (GAs) in Japan. Awareness of GTPTs was low in all groups, however, both CPs and FMs showed a higher degree of recognition in the benefits of GTPTs. FMs wanted information on germline findings to be shared more than the CPs. Since advanced CPs may have psychological burdens that make it difficult to express their opinions on their therapeutic options and sharing germline findings, GTPTs should be offered with advanced care planning for patients.

Informed consent is an essential part of an ethical clinical trial; to this end, researchers have developed several interventions to promote participants' full understanding of trials and thereby improve the consent process. However, few empirical studies have examined how patients make the decision of whether to give consent. The objective of this study, therefore, is to analyze patients' decision-making process when participating in clinical trials. We conduct an internet survey (n = 2,045) and interview data analysis (n = 40) with patients and categorize respondents into three types of participants: active, passive, and non-participation. Our results show that patients often make informal and quick decisions before medical staff provide them with relevant information during the informed consent process. For example, 55.9% of patients received initial information on clinical trials from an online article or web advertising, and 54.5% consulted no one about whether to participate in the clinical trial before making a decision. Only 20.7% of respondents subjectively spent time making the decision whether to participate; 43.0% of patients who said that they "spent time" coming to a decision took four or more days to reach a decision, while 8.3% of people who "did not spend time" making a decision took this among of time. Based on these results, we were able to break patients' decision-making process into four steps: first contact, informal decision making, relevant information, and formal decision making. Our results show that patients are most likely to make a decision based on the first information they receive on the clinical trial, whatever the source. To this end, having a list of questions for potential participants to ask researchers would be useful in helping better collecting information of clinical trials. In addition, research teams should give patients more than four days to decide between providing them with relevant information and obtaining written consent, even if the patient seems to make a quick decision.

The aim of this study was to assess public attitudes toward the promotion of genomic studies related to medicine and to examine the relationship between public attitudes and the level of genomic literacy by analyzing data from a nationwide opinion survey. The participants comprised 4,000 people (age, 20-69) selected from the Japanese general population by using the two-step stratified random sampling method. They were queried on the following topics in a mail survey: (1) pros and cons of the promotion of genomic studies related to medicine, (2) level of scientific literacy in genomics, (3) demographic and socioeconomic background, and (4) knowledge and attitudes toward science in general and genetic testing in particular. We examined the relationship between the approval of promotion and literacy level, using logistic regression models stratified by gender. Our results showed the response rate was 54.3% (2,171/4,000), and 69.4% participants favored the promotion of genomic studies related to medicine. Only 1.3% participants expressed a negative attitude. Multivariate analysis revealed that approval of promotion was related to a high literacy score. This relationship was stronger in males than in females (the highest quartile of score vs. the lowest: adjusted odds ratio, 3.36 for males and 1.86 for females; 95% confidence interval, 1.88-5.98 for males and 1.17-2.95 for females). We determined that a majority of the Japanese participants currently approved of the promotion of genomic studies related to medicine and that people with a high level of genomic literacy tended to approve the promotion.

BACKGROUND: The Fukushima Daiichi nuclear disaster caused a global panic by a release of harmful radionuclides. In a disaster setting, misusage of contemporary media sources available today can lead to disseminated incorrect information and panic. The study aims to build a scale which examines associations between media and individual anxieties, and to propose effective media usages for future disaster management. METHODS: The University of Tokyo collaborated with the Fukushima local government to conduct a radiation-health-seminar for a total of 1560 residents, at 12 different locations in Fukushima. A 13 item questionnaire collected once before and after a radiation-seminar was used on factor analysis to develop sub-scales for multiple regression models, to determine relationships between the sub-scales and media type consumed. A paired t-test was used to examine any changes in sub-scale of pre- and post-seminar scores. RESULTS: Three sub-scales were revealed and were associated with different media types: was with rumors, while concern for the future was positively associated with regional-newspapers and negatively with national-newspapers. Anxiety about social-disruption was associated with radio. The seminar had a significant effect on anxiety reduction for all the three sub-scales. CONCLUSION: Different media types were associated with various heightened concerns, and that a radiation seminar was helpful to reduce anxieties in the post-disaster setting. By tailoring post-disaster messages via specific media types, i.e., radio, it may be possible to effectively convey important information, as well as to calm fears about particular elements of post-disaster recovery and to combat rumors.

This paper introduces methods used to communicate with participants in the 'Biobank Japan Project (BBJP)', which is a disease-focused biobanking project. The methods and their implications are discussed in the context of the ethical conduct of the biobanking project. Informed consent, which ensures the autonomous decisions of participants, is believed to be practically impossible for the biobanking project in general. Consequently, the concept of 'trust', which is 'judgement and action in conditions of less than perfect information', has been suggested to compensate for this limitation. As a means to maintain the trust participants feel for the project, this paper proposes communication with participants after receiving their consent. After describing the limitations of informed consent within the BBJP, based on a survey we conducted, we introduce our attempts to communicate with participants, discussing their implications as a means to compensate for the limitations of informed consent at the biobanking project.

As of 2008, surrogacy is legal and openly practised in various places; Japan, however, has no regulations or laws regarding surrogacy. This paper reports the situation of surrogacy in Japan and in five other regions (the USA, the UK, Taiwan, Korea and France) to clarify the pros and cons of prohibiting surrogacy, along with the problems and issues relating to surrogacy compensation. Not only in a country such as France that completely prohibits surrogacy within the country, but also in a country such as the UK that allows non-commercial surrogacy, infertile couples travel overseas for the purpose of surrogacy. In addition, some couples might seek underground surrogacy if the government prohibits surrogacy. If an intended parent couple and a surrogate make an agreement among themselves and then a problem occurs, they cannot ask for support from professionals or bring a case to court, as can be observed in South Korea and Taiwan. We also conclude that there is little difference between commercial surrogacy and non-commercial surrogacy in the absence of a clear definition of 'reasonable expenses.' In the UK, the law does not allow surrogates to receive compensation. However, in reality, there may be little difference between the amounts paid to surrogates for profit in the US and those paid to surrogates for reasonable expenses in the UK. We conclude that the issue of surrogacy demands further discussion in Japan.

The regulation of direct-to-consumer genetic testing has till now focused on identifying predispositions to specific health problems and quality issues in testing, such as analytical and clinical validity criteria. In the United States, for example, the Food and Drug Administration warned that federal regulations for medical devices will apply to commercial genetic tests for health purposes. By contrast, the regulation of commercial genetic testing for other purposes is rarely discussed. These tests are advertised as identifying intelligence, athletic ability, and artistic sensibility in children. One company offers testing for a "gold medalist gene" purportedly associated with remarkable athletic talent; in Japan, the test has been favorably featured on some television programs and is recruiting customers through the Internet. Although a link between genetic background and individual performance has been noted, we are a long way from practical application of this data. But we should anticipate global interest in the pragmatic application of genetic knowledge, especially in East Asian countries, where private spending constitutes most of education investment. Concerned with this situation, the Japan Society of Human Genetics released an amended statement on consumer genetics at the end of 2010, adding warnings against "genetic testing for minors related to ability, character and future career paths" to its original 2008 statement on direct-to-consumer genetic testing for health purposes. The amendment also demands that JSHG members more actively share their information and perspectives on emerging genetic knowledge, not only with the public, but also with childhood education experts. The statement reflects growing concerns about several ethical considerations. First, the potential impact on the tested individual's life can be profound. Test results may discourage people from considering a particular career or employment without taking into account their interests or values. Conversely, an individual with the "right" genotype may be put under more pressure to perform well. Keeping in mind that the UNESCO Universal Declaration on the Human Genome and Human Rights warns us "not to reduce individuals to their genetic characteristics and to respect their uniqueness and diversity," those who develop genetic technologies and knowledge must be aware of the potential implications on collective social values. …