Kaori Muto

Overview of the BioBank Japan Project: Study design and profile

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.

The Relationship between Media Consumption and Health-Related Anxieties after the Fukushima Daiichi Nuclear Disaster

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.

Relationship between public attitudes toward genomic studies related to medicine and their level of genomic literacy in Japan

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.

Cross-sectional analysis of BioBank Japan clinical data: A large cohort of 200,000 patients with 47 common diseases

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.

For what am I participating? The need for communication after receiving consent from biobanking project participants: experience in Japan

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.

Overview of BioBank Japan follow-up data in 32 diseases

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.

Demographic and lifestyle factors and survival among patients with esophageal and gastric cancer: The Biobank Japan Project

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.

Statin use and all-cause and cancer mortality: BioBank Japan cohort.

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.

Characteristics and prognosis of Japanese male and female lung cancer patients : The BioBank Japan Project

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.

Characteristics and prognosis of Japanese colorectal cancer patients : The BioBank Japan Project

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.