Green tea consumption and risk of hematologic neoplasms: the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study)

PurposeExperimental studies suggested that green tea may have an anticancer effect on hematologic neoplasms. However, few prospective studies have been conducted.MethodsA total of 65,042 individuals aged 40–79 years participated in this study and completed a self-administered questionnaire about their lifestyle and medical history at baseline (1988–1990). Of these, 52,462 individuals living in 24 communities with information on incident hematologic neoplasms available in the cancer registry, who did not have a history of cancer and provided valid information on frequency of green tea consumption, were followed through 2009. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of hematologic neoplasms according to green tea consumption were analyzed.ResultsThe incidence of hematologic neoplasms during a median follow-up of 13.3 years was 323. Compared with the never-drinkers of green tea, the multivariate HRs and 95% CIs for total hematologic neoplasms in green tea drinkers of ≤ 2 cups/day, 3–4 cups/day, and ≥ 5 cups/day were 0.65 (0.42–1.00), 0.73 (0.47–1.13), and 0.63 (0.42–0.96), respectively. The association was more prominent for acute myeloid leukemias and follicular lymphomas.ConclusionsThe present cohort study suggests a protective effect of green tea against hematologic neoplasms, especially acute myeloid leukemias

Triple-negative pleomorphic lobular carcinoma and expression of androgen receptor: Personal case series and review of the literature

Pleomorphic lobular carcinoma (PLC) is a histological variant of invasive lobular carcinoma (ILC) and is associated with worse prognosis than classical ILC. It exhibits a greater degree of cellular atypia and pleomorphism and is occasionally accompanied with apocrine morphology. We investigated the immunohistochemical characteristics of samples from 31 Japanese patients with PLC to elucidate the clinicopathological characteristics of PLC including androgen receptor (AR) immunoreactivity. The surrogate molecular subtypes were luminal A-like, luminal B-like, luminal B-like/HER2, HER2-type, and triple-negative in 5, 4, 3, 5, and 14 cases, respectively. AR was positive in 92.8% (13/14) of the triple-negative PLC cases and 100% (10/10) of the non-triple-negative PLC cases. Disease-specific survival was worse in patients with histological grade 3 PLCs than in those with histological grade 2 PLCs (p = 0.007). However, there was no significant difference in the progression-free survival between the two groups (p = 0.152). No other clinicopathological characteristics were associated with prognosis. These results reveal that PLC exhibits various surrogate molecular subtypes and that the triple-negative subtype frequently expresses AR. The observed molecular apocrine differentiation implicates that triple-negative PLC can be categorized into the luminal AR subtype. Furthermore, AR-targeted therapy might be useful for patients with triple-negative PLC

VEGF Polymorphism rs3025039 and Human T-Cell Leukemia Virus 1 (HTLV-1) Infection among Older Japanese Individuals: A Cross-Sectional Study

Previous studies have reported a close correlation between vascular endothelial growth factor (VEGF), which plays an important role in angiogenesis, and human T-cell leukemia virus 1 (HTLV-1). However, an association between genetic characteristics related to VEGF and HTLV-1 infection has not yet been reported. Because the VEGF polymorphism rs3025039 is inversely associated with serum concentrations of VEGF, we focus on rs3025039 in the present study. To clarify the association between the VEGF polymorphism rs3025039 and HTLV-1 infection, a cross-sectional study of 1924 Japanese individuals aged 60–79 years who participated in general health check-ups was conducted. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) for HTLV-1 infection in relation to rs3025039 genotype were calculated with adjustment for known confounders. Compared with rs3025039 CC-homozygotes, (T) allele carriers had a significantly lower OR for HTLV-1 infection. The adjusted OR and 95% CI for HTLV-1 infection was 0.70 (0.54–0.91) (p = 0.009). Genetic characteristics related to lower angiogenesis activity might be associated with a lower chance of establishing HTLV-1 infection. Although further investigation is necessary, angiogenesis might play a crucial role in the establishment of HTLV-1 infection

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Human Error Prediction Using Heart Rate Variability and Electroencephalography

As human’s simple tasks are being increasingly replaced by autonomous systems and robots, it is likely that the responsibility of handling more complex tasks will be more often placed on human workers. Thus, situations in which workplace tasks change before human workers become proficient at those tasks will arise more frequently due to rapid changes in business trends. Based on this background, the importance of preventing human error will become increasingly crucial. Existing studies on human error reveal how task errors are related to heart rate variability (HRV) indexes and electroencephalograph (EEG) indexes. However, in terms of preventing human error, analysis on their relationship with conditions before human error occurs (i.e., the human pre-error state) is still insufficient. This study aims at identifying biological indexes potentially useful for the detection of high-risk psychological states. As a result of correlation analysis between the number of errors in a Stroop task and the multiple HRV and EEG indexes obtained before and during the task, significant correlations were obtained with respect to several biological indexes. Specifically, we confirmed that conditions before the task are important for predicting the human error risk in high-cognitive-load tasks while conditions both before and during tasks are important in low-cognitive-load tasks

Percentage of income spent on tobacco and intention to quit: a cross-sectional analysis of the JASTIS 2020 study

Background: Existing indicators for the ease of purchasing tobacco did not reflect the actual amount smoked and individual income, and did not assess heated tobacco products (HTPs). This study assessed the percentage of income spent on tobacco, including combustible cigarettes and/or HTPs, at the individual level and its relation to quit intention. Methods: An internet-based self-reported questionnaire survey was conducted in 2020 as a part of the Japan Society and New Tobacco Internet Survey. A total of 954 smokers aged 15–72 years were analyzed. We calculated the percentage of income spent on tobacco according to income levels. A high percentage implies that tobacco is not easy to purchase. The odds ratios for quit intention according to three categories of percentage of income spent on tobacco (5%) were calculated by multivariable logistic regression. Results: The percentage of income spent on tobacco was higher as income level was lower, especially for dual cigarette and HTP users; the percentages in the lowest/highest income group were 7.1%/1.2% for exclusive combustible cigarette smokers; 6.5%/1.1% for exclusive HTPs users; and 9.2%/1.3% for dual users. The adjusted odds ratios (95% confidence intervals) of quit intention among the >5% of income spent on tobacco group compared with the <1% spent group were 0.43 (0.18–1.03) for exclusive combustible cigarette smokers, 0.71 (0.20–2.54) for exclusive HTPs users, and 0.11 (0.02–0.77) for dual users. Conclusions: Higher tobacco expenditure was not associated with quit intention for all categories of tobacco product users, probably due to the low price of tobacco in Japan