The pentameric hydrocoel lobes organize adult pentameral structures in a sea cucumber, Apostichopus japonicus.

Despite being one of the bilaterians, the body plan of echinoderms shifts from bilateral symmetry to five-fold radial, or pentaradial symmetry during embryogenesis or their metamorphosis. While the clarification of the developmental mechanism behind this transition will be a basis for understanding their unique body plan evolution, it is still poorly understood. With this regard, the hydrocoel, a mesodermal coelom formed on the left side of bilateral larva, would be a clue for understanding the mechanism as it is the first pentaradial structure that appears before metamorphosis and develops into the water vascular system of adults. By analyzing the development of a sea cucumber, Apostichopus japonicus, we found that the hydrocoel expresses genes related in muscle and neural formation such as myosin heavy chain, tropomyosin, soxC, and elav, implying that cells of the hydrocoel contributes to muscle and neural structures in the adult. Furthermore, ablation of one of the hydrocoel lobes led to incomplete development of adult pentameral structures. The ablation of primary hydrocoel lobes resulted in the reduction in tentacles and the ablation of secondary hydrocoel lobes resulted in the reduction in water vascular canals and nerve cords. Our findings suggest that the hydrocoel lobes may serve as a potential organizing center for establishing the pentaradial body plan in echinoderms.

Expectations, concerns, and attitudes regarding whole-genome sequencing studies: a survey of cancer patients, families, and the public in Japan.

Whole-genome sequencing (WGS) is being used in research and clinical settings in cancer genomics. Studies show that cancer patients generally have positive attitudes toward tumor profiling tests; however, few works revealed their attitudes toward WGS. This study clarifies the expectations, concerns, and result preferences of cancer patients (CPs), family members (FMs) and general adults (GAs) regarding WGS study in Japan. We conducted an anonymous survey with 1204 CPs, 5958 FMs, and 2915 GAs in 2021. Despite low awareness of the WGS studies, CPs had the highest expectations for it. FMs had a higher level of concern than CPs and GAs; feeling anxious by knowing the results, being treated unfavorably if germline findings were detected. Both the FMs and CPs were highly concerned about the protection of genetic information. CPs preferred results with actionability, however, only half preferred to know germline findings. Given the possibility of detecting variants across multidisciplinary diseases and the long-term continuity of WGS research, a system is needed in which study participants can consult and receive decision-making support at any time according to their needs.

Is legislation to prevent genetic discrimination necessary in Japan? An overview of the current policies and public attitudes.

Genetic discrimination (GD) has not been discussed in East Asia as extensively as in Europe and North America. Influenced by UNESCO's universal declaration in 1997, the Japanese government took a stringent approach toward GD by releasing the Basic Principles on Human Genome Research in 2000. However, Japanese society has mostly been ignoring the prevention of GD for decades, and the principle of prohibiting GD was never adhered to in any of the Japanese laws. We conducted anonymous surveys among the general adult population in 2017 and 2022 to explore their experiences of GD and attitudes toward laws carrying penalties to prevent GD in Japan. In both years, approximately 3% of the respondents had experienced some unfavorable treatment regarding their genetic information. They showed higher recognition of the benefits of using genetic information and lower recognition of concerns about using genetic information and GD in 2022 than in 2017. However, the awareness regarding the need for legislation with penalties on GD had increased over the five-year period. In 2022, the framework of a bill to promote genomic medicine and prevent GD without any relevant penalties was released by the Bipartisan Diet Members Caucus. Considering that the absence of regulations may be a barrier to obtaining genomic medicine, as the initial step toward making the prohibition of GD more effective, legislation that no form of GD will be tolerated may stimulate education and awareness regarding respect for the human genome and its diversity.

Age-related differences in glenohumeral internal rotation deficit, humeral retrotorsion angle, and posterior shoulder tightness in baseball players.

BACKGROUND: Glenohumeral internal rotation deficit is generally recognized as a risk factor for throwing disability in baseball players. However, the pathology, timing of onset, role in the onset of humeral retrotorsion angle (HTA) and soft tissue extensibility (STE), and the relationship with age remain unclear. Therefore, the purpose of this cross-sectional study was to investigate age-related glenohumeral internal rotation deficit, HTA, and STE in Japanese baseball players and determine whether these factors correlate with throwing disability. METHODS: Participants were 172 male baseball players divided into a symptomatic group (n = 68) and an asymptomatic group (n = 104). The mean age at examination was 15.4 ± 3.2 (range, 8-22) years. Measurement items were range of motion of bilateral internal and external rotation at 90° abduction (2ndIR and 2ndER, respectively), bilateral HTA, and posterior shoulder muscle elasticity. Correlations of age, symptom, and dominance with these measurements were investigated, and significant bilateral differences in HTA and STE by age and symptom were analyzed. RESULTS: HTA and 2ndER of the dominant side were significantly greater than those of the nondominant side in those over the age of 13 years in both the asymptomatic and symptomatic groups. In contrast, 2ndIR of the dominant side was significantly smaller than that of the nondominant side in those over the age of 13 years in both the asymptomatic and symptomatic groups. The difference in HTA between the dominant and nondominant sides increased and then plateaued at 12° after the age of 16 years. STE was observed only in the symptomatic group, and the value of STE was significantly greater in players aged >16 years compared with that in players aged <12 years (P = .001). Muscle elasticity did not differ significantly between sides and showed no correlation with STE. CONCLUSIONS: The difference in HTA between the dominant and nondominant sides increased with age until 16 years old regardless of symptoms. STE in the dominant side was observed only in symptomatic baseball players after the age of 13 years and increased with age, plateauing around the age of 16 years. Posterior shoulder muscle elasticity was not indicated as a cause of STE.

Attitudes toward genomic tumor profiling tests in Japan: patients, family members, and the public.

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.

Correction: Attitudes toward genomic tumor profiling tests in Japan: patients, family members, and the public.

The version of this article originally published was not open access. This article should have been open access. The error has been fixed, and the article is now open access.

Survey on the perception of germline genome editing among the general public 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.

[National survey of municipalities examining the introduction of Honnintsuchiseido and its effect on the issuance of resident record copies for academic research].

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.

Serum glucose, cholesterol and blood pressure levels in Japanese type 1 and 2 diabetic patients: BioBank Japan.

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.

Clinical and histopathological characteristics of patients with prostate cancer in the BioBank Japan project.

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.

Characteristics and prognosis of Japanese female breast cancer patients: The BioBank Japan project.

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.

Characteristics of patients with liver cancer in the BioBank Japan project.

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.

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.

Survival of macrovascular disease, chronic kidney disease, chronic respiratory disease, cancer and smoking in patients with type 2 diabetes: BioBank Japan cohort.

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.

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.

Risk prediction models for mortality in patients with cardiovascular disease: The BioBank Japan project.

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.

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.

Cholesterol levels of Japanese dyslipidaemic patients with various comorbidities: BioBank Japan.

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 <6.0%, never smoker, chronic respiratory disease as a comorbidity and no medication use. CONCLUSIONS: These data provide details of serum cholesterol levels by risk-factor profile in patients with dyslipidaemia and could add evidence of treatment decisions.