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Background: The novel coronavirus disease 2019 (COVID-19) pandemic has significantly impacted end-of-life decisions for cancer patients in Japan, with disparities existing between preferred and actual care settings. Our study investigates the potential shifts in cancer death locations during the pandemic and if there were excess cancer deaths., Methods: Utilizing national mortality data from the Ministry of Health, Labour and Welfare from January 2012 to February 2023, we identified cancer deaths using International Classification of Disease, 10 th revision codes. We assessed death locations, including medical institutions, nursing facilities, and homes. The Farrington algorithm was employed to estimate expected death counts, and the differences between observed and expected counts were denoted as excess deaths., Results: From January 2018 to February 2023, there was consistently increase in the weekly observed cancer deaths. The presence of a definitive excess during the pandemic period remains uncertain. The percentage of deaths in medical institutions declined from 83.3% to 70.1%, while home deaths increased from 12.1% to 22.9%. Between April 2020 and February 2023, deaths in medical institutions frequently fell below the 95% prediction lower limit. Home deaths consistently exceeded the 95% prediction upper limit, with significant excess deaths reported annually., Conclusion: Our study found a shift in cancer death locations from medical institutions to homes in Japan during the COVID-19 pandemic. Our study did not confirm an overall increase in cancer deaths during this period. As with global trends, the profound shift from hospitals to homes in Japan calls for a comprehensive exploration to grasp the pandemic's multifaceted impact on end-of-life cancer care decisions.

Purpose: This study aimed to investigate the relationships of moderate-to-vigorous physical activity (MVPA) with all-cause and disease-specific mortality. We also investigated how the association between MVPA at leisure time (LT-MVPA) and health outcomes differs at different MVPA at work (WT-MVPA) levels., Methods: The 81,601 community-dwelling Japanese persons age 50-79 yr who responded to a questionnaire in 2000-2003 were followed until 2018. Cox proportional hazard model was used to examine the association of total MVPA with risks of all-cause, cancer, heart disease, stroke, and respiratory disease mortality. Then, we compared the mortality risk according to the tertile of LT-MVPA, stratified by the tertile of WT-MVPA., Results: During the 15.1 yr of average follow-up, 16,951 deaths were identified. Even total MVPA below the recommended volume (i.e., 0.1-1.49 MET·h·d -1 ) was associated with 11% to 24% reductions in all-cause (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.82-0.96) and heart disease mortality (HR, 0.76; 95% CI, 0.61-0.94), compared with no MVPA at all. The further reduced risks were seen in MVPA up to 10 MET·h·d -1 . The inverse association between LT-MVPA and mortality risks was more evident at lower WT-MVPA, which was also inversely associated with the risks., Conclusions: Health benefits were observed at low levels of MVPA and up to 10 MET·h·d -1 , although the fine threshold for excessive MVPA was not clear. LT-MVPA had distinct health benefits especially for persons with lower WT-MVPA., (Copyright © 2023 by the American College of Sports Medicine.)

The Japan Diabetes Society and the Japan Cancer Association launched a joint committee and published their "First Joint Committee Report on Diabetes and Cancer" in 2013, compiling recommendations for physicians and health-care providers as well as for the general population. In 2016, the "Second Joint Committee Report on Diabetes and Cancer" summarized the current evidence on glycemic control and cancer risk in patients with diabetes. The current "Third Joint Committee Report on Diabetes and Cancer", for which the joint committee also enlisted the assistance of the Japanese Society of Clinical Oncology and the Japanese Society of Medical Oncology, reports on the results from the questionnaire survey, "Diabetes Management in Patients Receiving Cancer Therapy," which targeted oncologists responsible for cancer management and diabetologists in charge of glycemic control in cancer patients. The results of the current survey indicated that there is a general consensus among oncologists and diabetologists with regard to the need for guidelines on glycemic control goals, the relevance of glycemic control, and glycemic control during cancer therapy in cancer patients., (© 2023 The Japanese Cancer Association (JCA) and The Japan Diabetes Society (JDS). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Cachexia is a common cancer complication and is associated with weight loss and anorexia. In this study, we investigated the ameliorating effects of cystine and theanine on cancer cachexia using a mouse model. In mice carrying the colon cancer cell line C-26, there was a suppression of body weight increase and reduction in both internal fat and lower limb muscles. Repeated cystine and theanine administration significantly prevented weight loss, internal fat loss, lower limb muscle loss, and serum IL-6 increase in the cachexia model. These results suggested that cystine and theanine may be effective in ameliorating cancer cachexia., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

This report summarizes the presentations and discussions in the first Asian Clinical Trials Network for Cancers (ATLAS) international symposium that was held on 24 April 2022, in Bangkok, Thailand, and hosted by the National Cancer Center Hospital (NCCH), co-hosted by the Pharmaceuticals and Medical Devices Agency (PMDA), Clinical Research Malaysia (CRM) and the Thai Society of Clinical Oncology (TSCO), and supported by Embassy of Japan in Thailand. Since 2020, the NCCH has conducted the ATLAS project to enhance research environments and infrastructures to facilitate international clinical research and cancer genomic medicine in the Asian region. The purpose of the symposium was to discuss what we can achieve under the ATLAS project, to share the latest topics and common issues in cancer research and to facilitate mutual understanding. Invitees included stakeholders from academic institutions, mainly at ATLAS collaborative sites, as well as Asian regulatory authorities. The invited speakers discussed ongoing collaborative research, regulatory perspectives to improve new drug access in Asia, the status of phase I trials in Asia, the introduction of research activities at the National Cancer Center (NCC) and the implementation of genomic medicine. As the next steps after this symposium, the ATLAS project will foster increased cooperation between investigators, regulatory authorities and other stakeholders relevant to cancer research, and establish a sustainable pan-Asian cancer research group to increase the number of clinical trials and deliver novel drugs to patients with cancer in Asia., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Although studies have found an association between chronic kidney disease (CKD) and cancer incidence, the results are inconsistent., Methods: This study included participants in the Japan Public Health Center-based Prospective Study who had data on serum creatinine measurements. We assessed the association between estimated glomerular filtration rate (eGFR) and the risk of total and site-specific cancer incidence using a systematic survey in Japan. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for participant demographics and lifestyle factors., Results: A total of 21 978 participants who met the inclusion criteria were followed up for a mean period of 12.9 years, during which a total of 2997 incident cancer cases were reported. In the multivariable adjusted models, an eGFR of <45 mL/min/1.73 m2 was not significantly associated with total cancer incidence (adjusted HR 1.22, 95% CI 0.94-1.60), compared with an eGFR of 60-89 mL/min/1.73 m2 (reference). The HR among those with eGFRs of ≥90 mL/min/1.73 m2 was 1.10 (95% CI 1.00-1.22)., Conclusions: In this large prospective study, a low eGFR was not significantly associated with an increased risk of total cancer incidence in patients with CKD, which may be partly due to an underpowered sample size. This finding may be due to the many shared risk factors between CKD and cancer., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Polytheonamide B (1) is an exceptionally large peptide that forms a transmembrane ion channel. The potent cytotoxicity of 1 against MCF-7 cancer cells originates from its two ion transport functions. Compound 1 depolarizes the plasma membrane and neutralizes acidic lysosomes. Here, we describe how we uncoupled these functions by designing and synthesizing new analogues of 1.

Purpose: To identify the factors associated with employment status among mothers of childhood cancer survivors (CCSs)., Methods: We conducted a questionnaire survey on mothers of survivors of childhood cancer to clarify practical factors such as care demands, psychological factors such as motivation to work, and support. After calculating descriptive statistics for all variables, binary logistic regression analysis was performed., Results: Of 171 mothers, 129 (75.4%) were employed. The most common form of employment was non-regular (n = 83; 48.5%), including part-time, dispatched, and fixed-term workers. At the time of the survey, compared with nonworking mothers, working mothers tended to be more motivated to work and have lower scores for "Long-term Uncertainty" on the Parent Experience of Child Illness Scale. The results of the binary logistic regression analysis indicated that employment was related to higher motivation to work, the continuation of employment during treatment, more outpatient visits, and a higher amount of support., Conclusion: As employment of CCSs' mothers is associated with psychological factors such as motivation to work and long-term uncertainty, psychological support for CCSs' mothers might promote employment. In addition, because the continuation of employment during treatment affects the employment of mothers after the end of cancer treatment, a leave system that covers the treatment period for childhood cancer needs to be established., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The number of long-term survivors after a cancer diagnosis is increasing. Few investigations have compared survivors' diets to their original pre-diagnosis dietary pattern or with the patterns of cancer-free controls. We examined the dietary changes in survivors for five years (i.e. before to after diagnosis) in cancer survivors, comparing them with cancer-free controls in a prospective cohort study in Japan. Using 1995-1998 for the baseline and 2000-2003 for the follow-up survey, a validated food frequency questionnaire was administered to 33,643 men and 39,549 women aged 45-74 years. During the follow-up period, 886 men and 646 women had developed cancer. Participants that had not been diagnosed with cancer served as controls. There was a greater decrease in the calorie intake (median change: - 168 kcal/d [Interquartile range: - 640, 278]) in male cancer survivors compared to controls (- 33 kcal/d [- 453, 380], P < .001). On comparison with cancer-free controls, multiple linear regression analysis revealed a significantly larger reduction in energy-adjusted ethanol intake for male cancer survivors (β =  - 0.36). There was no difference in changes in fruit and vegetable or red meat intake and no other significant differences in dietary changes between survivors and controls for either gender. This suggests that most dietary changes in survivors after cancer diagnosis are not systematically different from those that occur in people without a cancer diagnosis., (© 2023. The Author(s).)

The tumor suppressor protein, p53, is a critical molecule involved in cancer development. However, the association between p53 Arg72Pro polymorphism and cancer risk remains unclear, possibly due to the pro-tumor potential of p53 under metabolic stress. Here, we hypothesized that the p53 Arg72Pro polymorphism plays different roles during tumorigenesis by adiposity status. We measured baseline body mass index (BMI) and p53 Arg72Pro polymorphism for two case-cohorts, which included 4264 cancers with up to 20 years of follow-up. Multivariable-adjusted hazard ratios (HRs) and confidence intervals (CIs) were estimated using weighted Cox proportional-hazards method. Without consideration of adiposity status, p53 Arg72Pro polymorphism was not associated with cancer risk. However, proline (Pro) homozygous genotype conferred an increased cancer risk for individuals with a BMI <25 kg/m 2 (HR [95% CI]: 1.12 [1.00-1.26] for total cancer and 1.19 [1.02-1.38] for obesity-related cancer), but not for those with a BMI ≥ 25 kg/m 2 . The heterogeneous effect of p53 Arg72Pro polymorphism on cancer risk according to adiposity status was indicated (p heterogeneity : 0.07 for total cancer and 0.03 for obesity-related cancer). Furthermore, the association between overweight and cancer risk was only observed in arginine (Arg) carriers, but not in Pro homozygous carriers (p heterogeneity : 0.07 for total cancer and 0.02 for obesity-related cancer). Pro homozygous carriers were more likely to be predisposed to cancer than Arg carriers with normal-weight conditions. In addition, overweight was related to a higher cancer risk in Arg carriers than Pro homozygous carriers. Our findings may suggest the adiposity-dependent dual effects of p53 Arg72Pro polymorphism during tumorigenesis., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: A dose-response and nonlinear association between fruit and vegetable intake and mortality has been reported in Europe and the United States, but little is known about this association in Asia., Objectives: This study aimed to evaluate the association of fruit and vegetable intake with all-cause, cancer, cardiovascular, and respiratory disease mortality in a Japanese cohort., Methods: In the Japan Public Health Center-based prospective study, we included 94,658 participants (mean age: 56.4; 46.0% male) without cancer and cardiovascular disease at baseline. Information on fruit and vegetable intake was collected using a validated FFQ. The Cox proportional hazard model was used to estimate HRs and 95% CIs of each quintile of fruit and vegetable intake, separately, in relation to all-cause and cause-specific mortality using the first quintile as a reference. Nonlinear associations were evaluated using a likelihood ratio test, comparing a linear model with a restricted cubic spline model., Results: During a median of 20.9 follow-up years (IQR: 19.6-23.8 y), 23,687 all-cause deaths were documented. After adjusting for age, sex, and potential confounding factors, fruit and vegetable intake was nonlinearly and significantly associated with lower all-cause mortality, with the fourth and fifth quintiles having comparable HRs (fruit: fourth quintile HR: 0.91; 95% CI: 0.87, 0.95 and fifth quintile HR: 0.92; 95% CI: 0.88, 0.96; P-nonlinearity < 0.001; vegetable: fourth quintile HR: 0.92; 95% CI: 0.88, 0.97 and fifth quintile HR: 0.93; 95% CI: 0.89, 0.98; P-nonlinearity = 0.002). Fruit intake was significantly associated with lower cardiovascular mortality (HR in the fifth quintile: 0.91; 95% CI: 0.83, 0.99; P-nonlinearity = 0.01)., Conclusions: In the Japanese population, higher intake of fruits and vegetables was nonlinearly associated with decreased all-cause mortality. These findings may contribute to the establishment of dietary recommendations for enhancing life expectancy in Asia., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Sleep duration is emerging as an important modifiable risk factor for morbidity and mortality. We assessed the association between sleep duration and cancer incidence and mortality among Japanese adults using data from six population-based cohorts with 271 694 participants. During a total follow-up period of about 5.9 million person-years, we identified 40 751 incident cancer cases and 18 323 cancer deaths. We computed study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models and pooled the estimates using random-effects meta-analysis. Sleep duration of ≥10 hours (vs 7 hours) was associated with increased risk of cancer incidence among women (HR 1.19, 95% CI 1.02-1.38), but not men, and increased risk of cancer mortality among men (HR 1.18, 95% CI 1.00-1.39) and women (HR 1.44, 95% CI 1.20-1.73). Sleep duration of ≤5 hours (vs 7 hours) was not associated with cancer incidence and mortality. However, among postmenopausal women, sleep durations of both ≤5 and ≥10 hours (vs 7 hours) were associated with an increased risk of cancer mortality. Among Japanese adults, sleep duration of ≥10 hours is associated with increased risk of cancer incidence and mortality among women and cancer mortality among men., (© 2022 UICC.)

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces cancer cell death and contributes to tumor rejection by cytotoxic lymphocytes in cancer immunosurveillance and immunotherapy. TRAIL and TRAIL receptor agonists have garnered wide popularity as promising agents for cancer therapy. We previously demonstrated that the loss of fucosylation in cancer cells impairs TRAIL sensitivity; however, the precise structures of the fucosylated glycans that regulate TRAIL sensitivity and their carrier molecules remain elusive. Herein, we observed that Lewis glycans among various fucosylated glycans positively regulate TRAIL-induced cell death. Specifically, Lewis glycans on lacto/neolacto glycosphingolipids, but not glycoproteins including TRAIL receptors, enhanced TRAIL-induced formation of the cytosolic caspase 8 complex, without affecting the formation of the membranous receptor complex. Furthermore, type I Lewis glycan expression in colon cancer cell lines and patient-derived cancer organoids was positively correlated with TRAIL sensitivity. These findings provide novel insights into the regulatory mechanism of TRAIL-induced cell death and facilitate the identification of novel predictive biomarkers for TRAIL-related cancer therapies in future., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Due to recent increases in cancer burden worldwide, we investigated current awareness of cancer risk factors and the association between information sources and health behaviors for cancer prevention in Japan. A nationwide representative sample aged 20 years or older (563 men and 653 women) responded to a questionnaire as part of a population-based survey in December 2018. Tobacco smoking (55.7% of the mean attributable fraction of cancer risk overall) and cancer-causing infection (52.0%) were regarded more highly than other lifestyle factors as causes of cancer (obesity [36.6%], physical inactivity [31.9%], unbalanced diet [30.9%], and alcohol consumption [26.2%]). The association between information sources and health behaviors for cancer prevention was evaluated using a logistic regression model. The websites of public institutions, and health professionals were associated with a broad range of health behaviors including improving diet, exercise, cancer screening/health check-up, and abstinence from smoking/drinking. Among sources of print media, positive associations were observed between books and improving diet/exercise, brochures and cancer screening/health check-up, and advertisements and abstinence from smoking/drinking. A strategic health communication approach that utilizes various information sources and delivery channels is needed to inform the public about cancer prevention and to motivate risk-reducing behaviors in the population., (© 2022. The Author(s).)

(1) Background: Oxaliplatin is used as first-line chemotherapy not only for colorectal cancer but also for gastric and pancreatic cancers. However, it induces peripheral neuropathy with high frequency as an adverse event, and there is no effective preventive or therapeutic method. (2) Methods: The effects of omeprazole, a proton pump inhibitor (PPI), on oxaliplatin-induced peripheral neuropathy (OIPN) was investigated using an in vivo model and a real-world database. (3) Results: In a rat model, oxaliplatin (4 mg/kg, i.p., twice a week for 4 weeks) caused mechanical hypersensitivity accompanied by sciatic nerve axonal degeneration and myelin sheath disorder. Repeated injection of omeprazole (5−20 mg/kg, i.p., five times per week for 4 weeks) ameliorated these behavioral and pathological abnormalities. Moreover, omeprazole did not affect the tumor growth inhibition of oxaliplatin in tumor bearing mice. Furthermore, clinical database analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) suggests that the group using omeprazole has a lower reporting rate of peripheral neuropathy of oxaliplatin-treated patients than the group not using (3.06% vs. 6.48%, p < 0.001, reporting odds ratio 0.44, 95% confidence interval 0.32−0.61). (4) Conclusions: These results show the preventing effect of omeprazole on OIPN.

Background: Accumulating evidence suggests that consuming coffee may lower the risk of death, but evidence regarding tea consumption in Asians is limited. We examined the association between coffee and tea consumption and mortality in Asian populations., Methods: We used data from 12 prospective cohort studies including 248 050 men and 280 454 women from the Asia Cohort Consortium conducted in China, Japan, Korea and Singapore. We estimated the study-specific association of coffee, green tea and black tea consumption with mortality using Cox proportional-hazards regression models and the pooled study-specific hazard ratios (HRs) using a random-effects model., Results: In total, 94 744 deaths were identified during the follow-up, which ranged from an average of 6.5 to 22.7 years. Compared with coffee non-drinkers, men and women who drank at least five cups of coffee per day had a 24% [95% confidence interval (CI) 17%, 29%] and a 28% (95% CI 19%, 37%) lower risk of all-cause mortality, respectively. Similarly, we found inverse associations for coffee consumption with cardiovascular disease (CVD)-specific and cancer-specific mortality among both men and women. Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption., Conclusions: In Asian populations, coffee consumption is associated with a lower risk of death overall and with lower risks of death from CVD and cancer. Green tea consumption is associated with lower risks of death from all causes and CVD., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Epidemiological evidence on the effects of a long-term low-carbohydrate diet (LCD) on cancer incidence remains sparse. We investigate the association between LCD and the risk of overall and specific cancer site incidence in a Japanese population-based prospective cohort study among 90 171 participants aged 45-74. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median 17.0 y of follow-up, we identified 15 203 cancer cases. A higher overall LCD score was associated with increased overall cancer risk (HR = 1.08 [CI: 1.02-1.14], P-trend = .012), while it was associated with decreased gastric cancer (GC) risk (0.81 [0.71-0.93], P-trend = .006). A higher animal-based LCD score was associated with higher risk of overall cancer (1.08 [1.02-1.14], P-trend = .003), colorectal cancer (CRC) (1.11 [0.98-1.25], P-trend = .018), rectal cancer (RC) (1.24 [1.00-1.54], P-trend = .025), lung cancer (LC) (1.16 [1.00-1.34], P-trend = .042), and lower risk of GC (0.90 [0.79-1.01], P-trend = .033). Furthermore, we found that plant-based LCD score was related to lower GC incidence (0.87 [0.77-0.99], P-trend = .031). Additionally, adjusted for plant fat intake amplified the adverse associations (overall cancer: 1.08 [1.02-1.14] vs. 1.11 [1.05-1.18]; CRC: 1.08 [0.95-1.22] vs. 1.13 [0.99-1.30]; LC: 1.14 [0.98-1.33] vs. 1.19 [1.01-1.41]). We conclude that LCD enriching with animal products was associated with increased overall cancer, CRC, and LC incidence. These adverse associations could be attenuated by plant fat consumption. LCD reduces the risk of developing GC. Long-term adherence to LCD without paying attention to the balance between animal and plant food source consumption might cause adverse overall cancer incidence consequences., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

According to national cancer registry data in Japan, approximately 20,000 adolescents and young adults (AYAs, age 15-39 years) are newly diagnosed with cancer each year. Improvements in treatment and care for AYAs with cancer are included in the Phase Three Basic Plan to Promote Cancer Control Programs in Japan. This article reviews current cancer incidence and survival for AYAs with cancer in Japan using population-based cancer registry data. Mortality data through 2019 from the Vital Statistics of Japan are also described. Encouragingly, the 5-year survival probability for AYA cancers has continued to improve, in parallel with childhood cancers, and the mortality rate has decreased. There has been increasing attention to these vulnerable patients and improved partnerships and collaboration between adult and pediatric oncology; however, obstacles to the care of this population still exist at multiple levels. These obstacles relate to specific areas: research efforts and enrollment in clinical trials on AYA malignancies, AYA-specific psychosocial support such as education, financial support, and oncofertility care, and cancer care systems. It is important for Japanese oncologists, health care providers, and health policy makers to recognize that the AYA population remains vulnerable and still have unmet needs., (© 2021. The Author(s).)

Purpose: This study compared working cancer survivors' self-rated health status (SRHS), physical functional capacity, depressive symptoms, and happiness to those of cancer-free workers., Methods: A nationwide general population-based cross-sectional study on a sample of Japanese was conducted. Prevalence of deteriorated SRHS, restricted physical functional capacity, depressive symptoms, and perceived happiness were compared between working cancer survivors and cancer-free workers with multivariable logistic regression analysis adjusted for age and sociodemographic and health-related backgrounds., Results: Of the 28,311 male and 26,068 female workers, 977 (3.5%) and 1267 (4.9%) were cancer survivors, respectively. Working cancer survivors reported deteriorated SRHS more frequently than cancer-free workers: 21.3% vs. 13.8%, multivariable-adjusted odds ratio (95% confidence interval), 1.64 (1.39-1.95) for men, 23.8% vs. 17.5%, 1.34 (1.16-1.54) for women. Restricted physical functional capacity was reported more frequently in working cancer survivors than cancer-free workers: 6.8% vs. 2.6%, 1.76 (1.34-2.32) for men, 4.9% vs. 2.0%, 2.06 (1.56-2.71) for women. No significant difference was found for depressive symptoms: 21.6% vs. 22.9% in men, 30.0% vs. 28.5% in women. Working cancer survivors felt happiness more frequently than cancer-free survivors in men (77.3% vs. 71.7%, 1.21 (1.01-1.45)) but not in women (76.1% vs. 74.9%)., Conclusions: Working cancer survivors had worse SRHS and more restricted physical functional capacity than cancer-free workers. In men, working cancer survivors felt happiness more frequently than cancer-free workers., Implications for Cancer Survivors: Continuous support to improve cancer survivors' SRHS and physical functional capacity would be necessary even while they are working., (© 2021. The Author(s).)

Green tea is commonly consumed in China, Japan, and Korea and certain parts of North Africa and is gaining popularity in other parts of the world. The aim of this review was to objectively evaluate the existing evidence related to green tea consumption and various health outcomes, especially cancer, cardiovascular disease and diabetes. This review captured evidence from meta-analyses as well as expert reports and recent individual studies. For certain individual cancer sites: endometrial, lung, oral and ovarian cancer, and non-Hodgkins lymphoma the majority of meta-analyses observed an inverse association with green tea. Mixed findings were observed for breast, esophageal, gastric, liver and a mostly null association for colorectal, pancreatic, and prostate cancer. No studies reported adverse effects from green tea related to cancer although consuming hot tea has been found to possibly increase the risk of esophageal cancer and concerns of hepatotoxity were raised as a result of high doses of green tea. The literature overall supports an inverse association between green tea and cardiovascular disease-related health outcomes. The evidence for diabetes-related health outcomes is less convincing, while the included meta-analyses generally suggested an inverse association between green tea and BMI-related and blood pressure outcomes. Fewer studies investigated the association between green tea and other health outcomes such as cognitive outcomes, dental health, injuries and respiratory disease. This review concludes that green tea consumption overall may be considered beneficial for human health.

Background/objectives: The association of fermented soy products, separately from total soy products, with cardiovascular disease (CVD) and total cancer has not been reported. We examined this association in a population-based prospective cohort study in Japan., Subjects/methods: We studied 79,648 participants (42,788 women; 36,860 men) aged 45-74 years without a history of cancer, myocardial infarction, or stroke. Participants completed a food frequency questionnaire (1995-1998) and were followed to 2009-2012. Cox proportional hazards regression analysis was used to calculate the hazard ratios (HR) and 95% confidence intervals (CI) of incidence of CVD and total cancer according to quartiles of total soy products, nonfermented soy products, fermented soy products, miso soup, natto, total isoflavones from soy products, isoflavones from nonfermented soy products, and isoflavones from fermented soy products., Results: In women, we observed a significant inverse association between fermented soy product intake and the risk of CVD (multivariate HR in the highest compared with the lowest quartile of fermented soy product intake: 0.80; 95% CI: 0.68, 0.95; P for trend = 0.010), and also found significant inverse associations for natto and isoflavones among fermented soy products. In site-specific analysis, we observed a similar, significant inverse association between fermented soy product intake and the risk of stroke in women. We found no significant association between any soy product and risk of CVD in men or total cancer in both sexes., Conclusions: Intake of fermented soy products such as natto was inversely associated with the risk of CVD in women.

Background: Risk prediction models offer a promising approach to lifestyle modification. We evaluated the effect of personalized advice based on cancer risk prediction in improving five lifestyle habits (smoking, alcohol consumption, salt intake, physical activity, and body mass index) compared with standard advice without risk prediction among a Japanese general population with at least one unhealthy lifestyle habit., Methods: In a parallel-design, single-blind, randomized controlled trial between February 2018 and July 2019, 5984 participants aged 40-64 years with unhealthy lifestyle habits were recruited from persons covered under a life insurance policy. They were randomly assigned to an intervention or control group and received personalized or standard advice, respectively. They were also sent an invitation to participate in a lifestyle modification program aimed at improving lifestyle. Primary outcome was an improvement in lifestyle, defined as an increase in healthy lifestyle habits within 6 months., Results: The proportion of participants who improved their lifestyle within 6 months in the intervention group did not significantly differ from that in the control group (18.4% vs. 17.7%; P = 0.488). Among participants with low health literacy and two or fewer of five healthy habits, the proportion of participants subscribing to the lifestyle modification program was higher in the intervention group than in the control group., Conclusions: Compared with standardized advice, personalized advice based on cancer risk prediction had no effect on improving lifestyle., Impact: Provision of predicted cancer risk information did not induce change in unhealthy lifestyle., (©2021 American Association for Cancer Research.)

Abstract: Immune checkpoint inhibitors (ICIs) have emerged as evolutionary treatments for malignant diseases. Although ICIs can cause immune-related adverse events (irAEs) in various organs, precise timing after ICI initiation has been scarcely reported. Elucidating the effects of irAEs, such as time to onset, involvement of major organs, influence on progression-free survival (PFS), and overall survival (OS), are critical issues for physicians. Furthermore, lung-irAE as a whole is not well known.We conducted a retrospective study of 156 patients who were treated with ICIs and compared 82 irAE patients with 74 non-irAE patients.This study clearly demonstrated that the preferred period after induction of ICIs was significantly longer in lung-irAE than in other major organs (skin, digestive tract, and endocrine). The effect of irAEs on PFS and OS was evident PFS in the irAE group (n = 82) (median 128 days, interquartile range [IQR] 62-269 days, P = .002) was significantly longer than that in the non-irAE group (n = 74) (median 53 days, IQR 33-151 days). Similarly, OS was significantly longer in the irAE group (median 578 days, IQR 274-1027 days, P = .007) than in the non-irAE group (median 464 days, IQR: 209-842 days). However, this positive effect of irAEs in the lungs was not proportional to the extent of severity.Lung-irAEs can occur at a later phase than non-lung-irAEs and seemed not to prolong OS and PFS. However, further studies are needed to support these findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Little is known about the risk of cerebrovascular disease in cancer survivors. We aimed to assess the association between incident cancer and the subsequent risk of stroke using a large-scale, population-based prospective study. 74,530 Japanese aged between 40 and 69 years at baseline study were matched by the status of cancer diagnosis during follow-up using propensity score nearest-neighbor matching with allowance for replacement. A total of 2242 strokes were reported during 557,885 person-years of follow-up. Associations between incident cancer and the subsequent risk of all strokes, cerebral infarction, and intracerebral hemorrhage were assessed using a Cox proportional hazards model stratified on the propensity score-matched pairs. No significant association was observed between the status of cancer diagnosis of all types, gastric, colorectal and lung cancer, and subsequent occurrence of all strokes, cerebral infarction, and intracerebral hemorrhage. However, analysis by discrete time periods suggested an elevated risk in cancer patients for one to three months after a cancer diagnosis in all stroke (HR, 2.24; 95% CI, 1.06, 4.74) and cerebral infarction (HR, 2.62; 95% CI, 1.05, 6.53). This prospective cohort study found no association between the status of cancer diagnosis and the subsequent occurrence of all strokes and its subtypes during the entire follow-up period but suggested an increase in stroke risk during the active phase of malignancy.

Oxaliplatin is an essential drug in the chemotherapy of colorectal, gastric, and pancreatic cancers, but it frequently causes peripheral neuropathy as a dose-limiting factor. So far, animal models of oxaliplatin-induced peripheral neuropathy have been established. The mechanisms of development of neuropathy induced by oxaliplatin have been elucidated, and many drugs and agents have been proven to have neuroprotective effects in basic studies. In addition, some of these drugs have been validated in clinical studies for their inhibitory effects on neuropathy. In this review, we summarize the basic and clinical evidence for the therapeutic effects of oxaliplatin. In basic research, there are many reports of neuropathy inhibitors that target oxidative stress, inflammatory response, sodium channel, transient receptor potential (TRP) channel, glutamate nervous system, and monoamine nervous system. Alternatively, very few drugs have clearly demonstrated the efficacy for oxaliplatin-induced peripheral neuropathy in clinical trials. It is important to activate translational research in order to translate basic research into clinical research.

Purpose: As the prognosis of cancer patients deteriorates, secondary carcinogenesis after chemotherapy, especially secondary hematological malignancies, becomes a serious problem. However, information on the frequency and time of onset of secondary hematological malignancies and the risk of hematological malignancy with different drugs is scarce. This study aimed to evaluate the incidence of leukemia and myelodysplastic syndrome in patients with solid tumors, including breast, colon, gastric, pancreatic, small cell lung, non-small cell lung, esophageal, ovarian, cervical, and endometrial cancers., Methods: Using the United States Food and Drug Administration Adverse Event Reporting System, we analyzed the reporting rates, reporting odds ratios, and the reporting onset times of secondary leukemia and myelodysplastic syndrome for each drug used., Results: The leukemia reporting rates were higher in breast, small cell lung, ovarian, and endometrial cancers than in other cancers, and the myelodysplastic syndrome reporting rates were higher in ovarian and endometrial cancers than in other cancers. For each cancer type, the reporting odds ratios of cytocidal anticancer agents, such as taxanes, anthracyclines, alkylating agents, platinum, and topoisomerase inhibitors, were higher than those of other drugs. Alternatively, the reporting odds ratios of molecular targeted drugs and immune checkpoint inhibitors were not higher than those of other drugs. Approximately half of the cases of leukemia and myelodysplastic syndrome were reported within 1 to 4 years after chemotherapy., Conclusions: Our study clarified the risks of leukemia and myelodysplastic syndrome for several anticancer drugs in patients with solid tumors. Our data may aid in the assessment of the risks of secondary leukemia and myelodysplastic syndrome when medical oncologists, clinical pharmacists, and patients select chemotherapy regimens.

Purpose: We examined the association between meat intake and mortality due to all-cause and major causes of death using a population-based cohort study in Japan., Methods: 87,507 Japanese aged between 45 and 74 years old at 5-year follow-up study were followed for 14.0 years on average. Associations between meat intake and mortality risk were assessed using a Cox proportional hazards model., Results: A heavy intake of total meat was associated with a higher risk of all-cause mortality relative to the lowest quartile intake in men (Q4: HR,1.18; 95%CIs, 1.06-1.31). A higher intake of total meat was associated with a lower risk of stroke mortality in women (Q2: HR, 0.70; 95%CIs, 0.51-0.94, Q3: HR, 0.68; 95%CIs, 0.50-0.95, Q4: HR, 0.66; 95%CIs, 0.44-0.99). A heavy intake of red meat was also associated with all-cause mortality (Q4: HR, 1.13; 95%CIs, 1.02-1.26) and heart disease mortality (Q4: HR, 1.51; 95%CIs, 1.11-2.06) in men but not in women. Heavy intake of chicken was inversely associated with cancer mortality in men., Conclusions: Heavy intakes of total and red meat were associated with an increase in all-cause and heart disease mortality in men, while total meat intake was associated with a lower risk of stroke mortality in women., Competing Interests: The authors have declared that no competing interests exist.

Family history (FH) of cancer is an important factor of increased risk of several cancers. Although the association between FH of cancer and concordant cancer risk has been reported in many previous epidemiological studies, no comprehensive prospective study with adjustment for lifestyle habits has evaluated the association of FH of cancer and concordant cancer risk. We investigated the association between FH of cancer and concordant cancer risk in a Japanese population-based prospective study, initiated in 1990 for cohort I and in 1993 for cohort II. We analyzed data on 103,707 eligible subjects without a history of cancer who responded to a self-administered questionnaire including FH of cancer at baseline. Study subjects were followed through 2012 and analyzed using multivariable-adjusted Cox proportional hazards regression models. During 1,802,581 person-years of follow-up, a total of 16,336 newly diagnosed cancers were identified. Any site (Hazard ratios = 1.11 (95% confidence interval = 1.07-1.15]), esophagus (2.11 [1.00-4.45]), stomach (1.36 [1.19-1.55]), liver (1.69 [1.10-2.61]), pancreas (2.63 [1.45-4.79]), lung (1.51 [1.14-2.00]), uterus (1.93 [1.06-3.51]) and bladder cancers (6.06 [2.49-14.74]) with FH of the concordant cancer were associated with an increased risk compared to those without FH. Our findings suggest that having FH of cancer is associated with an increased risk of several concordant cancer incidences in an Asian population. Enquiring about FH of several types of cancer may be important in identifying groups at high-risk of those cancers., (© 2019 UICC.)

Purpose: Immune checkpoint inhibitors (ICIs) show promising clinical activity in advanced cancers. However, the safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies (ANA) are unclear., Methods: 191 patients treated with nivolumab, pembrolizumab, atezolizumab, or durvalumab for unresectable advanced cancers between September 2014 and December 2018 were identified retrospectively. Patients were divided into positive (ANA titers ≥ 1:160) and negative ANA groups (ANA titers < 1:160). Development of immune-related adverse events (irAEs), the overall response rate (ORR), and disease control rate (DCR) were monitored., Results: Positive ANA titers were seen in 9 out of 191 patients. Four patients in the positive ANA group and 69 patients in the negative group developed irAEs of any grade without a significant difference between the groups. The development of endocrine, pulmonary, and cutaneous irAEs was not significant, whereas positive ANA was significantly higher in patients who developed colitis (2/9) than in patients who did not (3/182, P = 0.0002). DCR in the positive and negative ANA group was 37.5% and 67.5%, respectively, and was not statistically significant, but had better efficacy in patients without ANA (P = 0.08). ANA-related autoimmune diseases such as SLE, Sjögren's syndrome, MCTD, scleroderma, dermatomyositis, and polymyositis was not induced in either group. However, one patient with preexisting dermatomyositis had a flare up after initiation of atezolizumab., Conclusion: Further studies to identify predictive factors for the development of irAEs are required to provide relevant patient care and maximize the therapeutic benefits of ICIs.

Although occupational sitting time has been associated with adverse health outcomes and mortality, the association with cancer incidence remains unknown. This study investigated the association between occupational sitting time and risk of total and site-specific cancer in a Japanese population. We evaluated 33 307 participants aged 50-79 years who responded to a questionnaire in 2000-2003 in the Japan Public Health Center-based Prospective Study and were followed until 2013. Participants were grouped by sitting time at work. Hazard ratio (HR) and 95% confidence interval (CI) of cancer incidence were calculated with adjustment for potential confounders including moderate-to-vigorous physical activity. During 10.2 years of follow-up, 3807 newly diagnosed cases of cancer were identified. Occupational sitting time was marginally associated with total cancer, with multivariable HRs for the ≥7 h/d vs 1 to <3 h/d category of 1.12 (95% CI, 0.99-1.26; P for trend = .071) in men, but not women. Among findings for cancers at specific sites, long occupational sitting time was associated with increased risk of pancreas cancer, with multivariable HRs for the ≥7 h/d vs 1 to <3 h/d category of 2.25 (95% CI, 1.17-4.34; P for trend = .021) in men, and lung cancer, with multivariable HRs for the ≥7 h/d vs 1 to <3 h/d category of 2.80 (95% CI, 1.33-5.90; P for trend = .013) in women. Extended sitting time at work was associated with an increased risk of pancreas cancer in men and lung cancer in women., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Earlier cohort studies using conventional regression models have consistently shown an increased cancer risk among individuals with type 2 diabetes. However, reverse causality and residual confounding due to common risk factors could exist, and it remains unclear whether diabetes per se contributes to cancer development. Mendelian randomization analyses might clarify the true association between diabetes and cancer risk. We conducted a case-cohort study with 10,536 subcohort subjects and 3,541 newly diagnosed cancer cases derived from 32,949 eligible participants aged 40-69 years within the Japan Public Health Center-based Prospective Study. With 29 known type 2 diabetes susceptibility variants, we used an inverse variance-weighted method to estimate hazard ratios for the associations of diabetes with risks of total and site-specific cancers. The hazard ratios of cancer per doubling of the probability of diabetes were 1.03 (95% confidence interval [CI], 0.92-1.15) overall, 1.08 (95% CI: 0.73-1.59) for the pancreas, 0.80 (95% CI: 0.57-1.14) for the liver and 0.90 (95% CI: 0.74-1.10) for the colorectum. Additional analyses, using publicly available large-scale genome-wide association study data on colorectal cancer in Japan, resulted in a narrower CI (hazard ratio: 1.00; 95% CI: 0.93-1.07). In this prospective Mendelian randomization study with a large number of incident cancer cases, we found no strong evidence to support associations between diabetes and overall and site-specific cancer risks. Our findings suggest that there is little evidence to support the genetic role of type 2 diabetes in cancer development in the Japanese population., (© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The aim of our study was to assess the association between green tea consumption and all-cause and cause-specific mortality in a pooled analysis of eight Japanese population-based cohort studies. Pooled hazard ratios (HR) and 95% confidence intervals (CI), derived from random effects models, were used to evaluate the associations between green tea consumption, based on self-report at baseline, and risk of all-cause and cause-specific mortality. During a mean follow-up of 17.3 years, among 313,381 persons, 52,943 deaths occurred. Compared with individuals who consumed < 1 cup/day, those in the highest consumption category (≥ 5 cups/day) had a decreased risk of all-cause mortality [the multivariate-adjusted HR was 0.90 (95% CI 0.87-0.94) for men and 0.82 (0.74-0.90) for women]. A similar inverse association was observed for heart disease mortality [HR 0.82 (0.75-0.90) for men, and 0.75 (0.68-0.84) for women], and cerebrovascular disease mortality [HR 0.76 (0.68-0.85) for men, and 0.78 (0.68-0.89) for women]. Among women, green tea consumption was associated with decreased risk of total cancer mortality: 0.89 (0.83-0.96) for the 1-2 cups/day category and 0.91 (0.85-0.98) for the 3-4 cups/day category. Results for respiratory disease mortality were [HR 0.75 (0.61-0.94)] among 3-4 cup daily consumers and [HR 0.66 (0.55-0.79)] for ≥ 5 cups/day. Higher consumption of green tea is associated with lower risk for all-cause mortality in Japanese, especially for heart and cerebrovascular disease. Moderate consumption decreased the risk of total cancer and respiratory disease mortality in women.

Objective: To study the association of educational level and risk of death from all causes, cardiovascular disease (CVD) and cancer among Asian populations., Design: A pooled analysis of 15 population-based cohort studies., Setting and Participants: 694 434 Asian individuals from 15 prospective cohorts within the Asia Cohort Consortium., Interventions: None., Main Outcome Measures: HRs and 95% CIs for all-cause mortality, as well as for CVD-specific mortality and cancer-specific mortality., Results: A total of 694 434 participants (mean age at baseline=53.2 years) were included in the analysis. During a mean follow-up period of 12.5 years, 103 023 deaths were observed, among which 33 939 were due to cancer and 34 645 were due to CVD. Higher educational levels were significantly associated with lower risk of death from all causes compared with a low educational level (≤primary education); HRs and 95% CIs for secondary education, trade/technical education and ≥university education were 0.88 (0.85 to 0.92), 0.81 (0.73 to 0.90) and 0.71 (0.63 to 0.80), respectively (p trend =0.002). Similarly, HRs (95% CIs) were 0.93 (0.89 to 0.97), 0.86 (0.78 to 0.94) and 0.81 (0.73 to 0.89) for cancer death, and 0.88 (0.83 to 0.93), 0.77 (0.66 to 0.91) and 0.67 (0.58 to 0.77) for CVD death with increasing levels of education (both p trend <0.01). The pattern of the association among East Asians and South Asians was similar compared with ≤primary education; HR (95% CI) for all-cause mortality associated with ≥university education was 0.72 (0.63 to 0.81) among 539 724 East Asians (Chinese, Japanese and Korean) and 0.61 (0.54 to 0.69) among 154 710 South Asians (Indians and Bangladeshis)., Conclusion: Higher educational level was associated with substantially lower risk of death among Asian populations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Coffee consumption is increasing globally. We aimed to assess the effect of coffee consumption on the risk of all-cause and cause-specific mortality in a pooled analysis of eight population-based cohort studies in Japan (Japan Cohort Consortium). Data came from eight Japanese cohort studies (144,750 men and 168,631 women). During a mean follow-up time of 17 years, 52,943 deaths occurred. More specifically, 19,495 cancer deaths, 7321 deaths due to heart disease, 6387 cerebrovascular, 3490 respiratory disease and 3382 injuries and accidents. A random effects model was applied to obtain pooled hazard ratios (HRs) and 95% confidence intervals (95%CIs). In both sexes, coffee consumption up to 5 cups/day was overall protective in relation to all-cause mortality, with the association attenuating in the highest category of coffee consumption (≥5 cups/day). In men, a similar inverse association was observed for major causes of mortality except cancer. In women, coffee consumption decreased the risk for mortality due to heart disease in the 1-2 cups/day category, but increased the risk in the ≥5 cups/day category. Coffee consumption was not associated with cancer in both sexes. Results were similar among male current smokers and female never-smokers. Based on available data, this pooled analysis suggests that coffee consumption under five cups per day may be beneficial for reducing the risk of mortality due to major causes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Drug screening-i.e., testing the effects of a number of drugs in multiple cell lines-is used for drug discovery and development, and can also be performed to evaluate the heterogeneity of a disease entity. Notably, intertumoral heterogeneity is a large hurdle to overcome for establishing standard cancer treatment, necessitating disease models better than conventional established 2D cell lines for screening novel treatment candidates. In the present review, we outline recent progress regarding experimental cancer models having more physiological and clinical relevance for drug screening, which are important for the successful evaluation of cellular response to drugs. The review is particularly focused on drug screening using the cancer organoid model, which is emerging as a better physiological disease model than conventional established 2D cell lines. We also review the use of cancer organoids to examine intertumor and intratumor heterogeneity, and introduce the perspective of the clinical use of cancer organoids to enable precision medicine.

Background & Aims: Cruciferous vegetables contain isothiocyanates, which effectively reduce inflammation and oxidative stress related to chronic diseases, inhibit the bioactivation of procarcinogens, and enhance the excretion of carcinogens. However, at present, no large cohort studies have investigated the effect of cruciferous vegetable on mortality. We aimed to examine the association between cruciferous vegetable intake and all-cause mortality, namely cancer, heart disease, cerebrovascular disease, and injuries, in a large cohort study conducted between 1990 and 1993, in Japan., Methods: The analysis included 88,184 participants (age: 45-74 years) with no history of cancer, myocardial infarction, and stroke. Participants were tracked for a median of 16.9 years, during which 15,349 deaths were occurred. The association between cruciferous vegetable intake and risk of all-cause and cause-specific mortality was determined by Cox proportional hazard regression analysis to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs), after adjustment for potential confounding factors., Results: An inverse association was found between cruciferous vegetable intake and total mortality in both gender. HRs (95% CI) for all-cause mortality in the highest compared to the lowest quintile were 0.86 (0.80, 0.93) for men (P = 0.0002 for trend) and 0.89 (0.81, 0.98) for women (P = 0.03 for trend). Cruciferous vegetable intake was associated with lower cancer mortality in men, as well as with heart disease-, cerebrovascular disease-, and injury-related mortality in women., Conclusions: This prospective study suggests that a higher cruciferous vegetables intake is associated with reduced risk of all-cause mortality., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

To elucidate the individual impacts of insulin and blood glucose on cancer risk, we investigated the association of plasma C-peptide, a surrogated marker of insulin and glycated albumin (GA), a more stable marker of blood glucose, with all-site and site-specific cancer risk by mutually accounting for their confounding effects. The study was prospectively conducted with nearly 4,000 cancer cases arising in our population-based cohort of 33,736 subjects who answered the baseline questionnaire and supplied blood samples. After exclusion of subjects with apparent DM, analysis was done in 3,036 cancer cases and 3,667 subcohort subjects. Among men and women combined, highest levels of C-peptide were statistically significantly associated with an increased risk of all-site [Hazard ratio (HR): 1.21; 95% confidence interval: 1.02-1.42], colon [1.73; 1.20-2.47], liver [3.23; 1.76-5.91], kidney, renal pelvis and ureter cancers [2.47; 1.07-5.69], compared to the respective lowest levels, after adjustment for GA levels. Among these C-peptide-related cancers, colon and liver cancers also showed an increased risk associated with elevated GA levels independently of C-peptide levels. The corresponding HRs for colon and liver cancers compared to the highest and lowest GA levels were 1.43 [1.02-2.00] and 2.02 [1.15-3.55], respectively. Effect modification by gender was only evident for the association between C-peptide and colon cancer (p for interaction = 0.04). Higher insulin levels, independently of higher blood glucose levels, may be relevant to DM-related carcinogenesis for several cancer sites. Examination of circulating insulin levels is a plausible option in evaluating cancer risk even in individuals who have not developed DM., (© 2018 UICC.)

The idea of tumor dormancy originated from clinical findings that recurrence of cancer occurs several years or even several decades after surgical resection of the primary tumor. Tumor mass dormancy was proposed as a model, where there is equal balance between increases in the number of cancer cells by proliferation and decreases as a result of cell death. Tumor mass dormancy includes angiogenic dormancy and immune-mediated dormancy. Another emerging type of tumor dormancy is cellular dormancy in which cancer cells are in a quiescent state. Cellular dormancy is induced by cues such as the extracellular matrix environment, metastatic niches, a hypoxic microenvironment, and endoplasmic reticulum stress. Even the oncogenic pathways, on which active cancer cells depend for survival and growth, are suppressed in the dormant state. As tumor dormancy is one of the mechanisms of resistance against various cancer therapies, targeting dormant cancer cells should be considered for future treatment strategies., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: In Japan, freeze-dried live attenuated varicella-zoster vaccine is available for adults aged ≥50 years to prevent herpes zoster. However, limited evidence has been accumulated regarding vaccine safety for patients with underlying illnesses, who have been considered as the high-risk group for herpes zoster., Methods: A prospective cohort study of 1200 healthy adults and 300 patients with underlying illnesses such as malignancy, diabetes mellitus, autoimmune diseases, and renal diseases was conducted. All subjects were vaccinated and then their adverse events (AEs) were followed for 28 days after vaccination. Key safety measures included any AEs, severe AEs (SAEs), and vaccine-related AEs such as injection-site AEs and systemic AEs. The frequencies and 95% confidence intervals of AEs were calculated., Results: During the follow-up period, 2 SAEs (bone fracture and acute cholecystitis) among healthy adults and 1 SAE (disseminated mycobacteriosis) among patients with underlying illnesses were reported, although none of them was diagnosed as vaccine-related. Vaccine-related AEs were reported in 42% of healthy adults and patients with underlying illnesses, and the proportions were similar between the groups. The most frequent AEs were injection-site AEs in both groups (i.e., 41 and 39%), and systemic AEs were observed in 4% of both groups. Only among healthy adults, those with a history of herpes zoster were more likely to report injection-site AEs than those without a history of herpes zoster (53% vs 39%)., Conclusions: The present study confirmed the safety of freeze-dried, live attenuated varicella-zoster vaccine even in patients with underlying illnesses. A history of herpes zoster might be related to development of injection-site AEs in healthy adults., Trial Registration: The study was prospectively registered on Japic-Clinical Trials Information as JapicCTI-163415 on October 31, 2016.

Tumor angiogenesis inhibition is one of the most potent strategies in cancer chemotherapy. From past clinical studies, inhibition of the vascular endothelial growth factor pathway successfully treats malignant tumors. However, vascular endothelial growth factor inhibitors alone cannot cure tumors. Moreover, resistance to small molecule inhibitors has also been reported. Herein, we show the antiangiogenic potential of a newly synthesized curcumin analog, GO-Y078, that possibly functions through inhibition of actin stress fiber formation, resulting in mobility inhibition; this mechanism is different from that of vascular endothelial growth factor inhibition. In addition, we examined the detailed mechanism of action of the antiangiogenesis potential of GO-Y078 using human umbilical venous epithelial cells resistant to angiogenesis inhibitors (HUVEC-R). GO-Y078 inhibited the growth and mobility of HUVEC-R at 0.75 μmol/L concentration. Expression analyses by microarray and RT-PCR showed that expressions of genes including that of fibronectin 1 were significantly suppressed. Among these genes, fibronectin 1 is abundantly expressed and, therefore, seems to be a good target for GO-Y078. In a knockdown experiment using Si-oligo of fibronectin 1 (FN1), FN1 expression was decreased to half of that in mock experiments as well as GO-Y078. Knockdown of FN1 resulted in the suppression of HUVEC-R growth at 24 hours after treatment. Fibronectin is a key molecule contributing to angiogenesis that could be inhibited by GO-Y078. Thus, resistance to vascular endothelial growth factor inhibition can be overcome using GO-Y078., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

A comprehensive evidence-based cancer prevention recommendation for Japanese was developed. We evaluated the magnitude of the associations of lifestyle factors and infection with cancer through a systematic review of the literature, meta-analysis of published data, and pooled analysis of cohort studies in Japan. Then, we judged the strength of evidence based on the consistency of the associations between exposure and cancer and biological plausibility. Important factors were extracted and summarized as an evidence-based, current cancer prevention recommendation: 'Cancer Prevention Recommendation for Japanese'. The recommendation addresses six important domains related to exposure and cancer, including smoking, alcohol drinking, diet, physical activity, body weight and infection. The next step should focus on the development of effective behavior modification programs and their implementation and dissemination.

Privacy preserving data mining for medical information is an important issue to guarantee confidentiality of integrated multiple data sets. In this paper, we propose a secured scheme to estimate related risk of cancers accurately and effectively in a privacy-preserving way. We study models to configure the appropriate set of attributes to reduce risk of identity of an individual from being determined. We examine the proposed privacy preserving protocol for encrypted hypothesis test, using actual cohort data supplied by National Cancer Center.

Background: Although East Asia is one of the largest tobacco-epidemic regions in the world, only a few prospective studies from Asia have investigated the impact of smoking and cessation of smoking on cancer. We aimed to assess the effect of cessation of smoking on the risk of cancer using eight population-based cohort studies in Japan., Methods: We analyzed pooled data from eight population-based prospective cohort studies in Japan with more than 320,000 participants to assess the effect of smoking cessation on the risk of total cancers and smoking-related cancers., Results: After adjustment for potential confounders, cancer risks in men with >21years of smoking cessation before baseline were found to decrease to the same level as never smokers for total cancer (never smokers: reference; former smokers with ≥21 years since smoking cessation: HR, 1.01; 95%CI: 0.91, 1.11). Even men who are heavy smokers (more than 20 pack-years) reported a reduced risk of total cancer (never smokers: reference; former smokers with ≥21 years since smoking cessation: HR, 1.06; 95%CI: 0.92, 1.23). In women, the risk of total cancer did not differ from that of never smokers after 11 years of smoking cessation before baseline (never smokers: reference; former smokers with ≥11 years since smoking cessation: HR, 0.96; 95%CI: 0.74, 1.23)., Conclusions: Our study suggests that longer duration of smoking cessation may attenuate the risk of cancer in both men and women, and that even heavy smokers (more than 20 pack-years) were found to benefit from quitting smoking., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Evidence regarding stress as a risk factor for cancer onset is inconsistent. In this study, based on the Japan Public Health Center-based Prospective Study, we enrolled 101,708 participants aged 40-69 years from 1990-1994. The self-reported perceived stress level was collected at baseline and updated through 5-year follow-up. The association between perceived stress and cancer risk was measured by Cox proportional hazards regression model, adjusted for all known confounders. During follow-up (mean = 17.8 years), we identified 17,161 cancer cases. We found no association between baseline perceived stress level and cancer incidence. However, by taking account of the dynamic changes in perceived stress, time-varying analyses revealed a slightly (4-6%) increased overall cancer risk for subjects under elevated perceived stress levels compared to the 'low stress level' group. Analyses concerning long-term perceived stress level showed that individuals with constantly high perceived stress level had an 11% (95% confidence interval 1-22%) excess risk for cancer compared to subjects with persistently low stress levels. This association was confined to men (20% excess risk), and was particularly strong among smokers, alcohol drinkers, obese subjects, and subjects without family history of cancer. Therefore, we concluded high perceived stress level might contribute to excess overall cancer incidence among men.

Background/aim: We investigated the relationship between the expression of natural killer group 2, member D ligands (NKG2DLs) and the antitumor effects of protein-bound polysaccharide-K (PSK)., Materials and Methods: PSK was administered to evaluate its effectiveness against tumor growth. The expression of Rae-1 and H60 were analyzed in multiple cell lines., Results: PSK showed the highest antitumor effects in mice implanted with cells expressing neither Rae-1 nor H60. PSK had little antitumor effect in mice implanted with cells expressing both Rae-1 and H60. A correlation between the expression of NKG2DLs and the antitumor effect of PSK was observed. After PSK administration, INF-γ production in CD8 + T cells increased in mice with cells expressing neither Rae-1 nor H60, but did not change in mice implanted with cells expressing both Rae-1 and H60., Conclusion: We demonstrated that the expression of NKG2DLs affects tumor immunity and the efficacy of immuno therapy in tumor-bearing mouse model., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aims/hypothesis: The aims of the study were to evaluate the association between type 2 diabetes and the risk of death from any cancer and specific cancers in East and South Asians., Methods: Pooled analyses were conducted of 19 prospective population-based cohorts included in the Asia Cohort Consortium, comprising data from 658,611 East Asians and 112,686 South Asians. HRs were used to compare individuals with diabetes at baseline with those without diabetes for the risk of death from any cancer and from site-specific cancers, including cancers of the oesophagus, stomach, colorectum, colon, rectum, liver, bile duct, pancreas, lung, breast, endometrium, cervix, ovary, prostate, bladder, kidney and thyroid, as well as lymphoma and leukaemia., Results: During a mean follow-up of 12.7 years, 37,343 cancer deaths (36,667 in East Asians and 676 in South Asians) were identified. Baseline diabetes status was statistically significantly associated with an increased risk of death from any cancer (HR 1.26; 95% CI 1.21, 1.31). Significant positive associations with diabetes were observed for cancers of the colorectum (HR 1.41; 95% CI 1.26, 1.57), liver (HR 2.05; 95% CI 1.77, 2.38), bile duct (HR 1.41; 95% CI 1.04, 1.92), gallbladder (HR 1.33; 95% CI 1.10, 1.61), pancreas (HR 1.53; 95% CI 1.32, 1.77), breast (HR 1.72; 95% CI 1.34, 2.19), endometrium (HR 2.73; 95% CI 1.53, 4.85), ovary (HR 1.60; 95% CI 1.06, 2.42), prostate (HR 1.41; 95% CI 1.09, 1.82), kidney (HR 1.84; 95% CI 1.28, 2.64) and thyroid (HR 1.99; 95% CI 1.03, 3.86), as well as lymphoma (HR 1.39; 95% CI 1.04, 1.86). Diabetes was not statistically significantly associated with the risk of death from leukaemia and cancers of the bladder, cervix, oesophagus, stomach and lung., Conclusions/interpretation: Diabetes was associated with a 26% increased risk of death from any cancer in Asians. The pattern of associations with specific cancers suggests the need for better control (prevention, detection, management) of the growing epidemic of diabetes (as well as obesity), in order to reduce cancer mortality.

Importance: Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning., Objective: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015., Evidence Review: Cancer mortality was estimated using vital registration system data, cancer registry incidence data (transformed to mortality estimates using separately estimated mortality to incidence [MI] ratios), and verbal autopsy data. Cancer incidence was calculated by dividing mortality estimates through the modeled MI ratios. To calculate cancer prevalence, MI ratios were used to model survival. To calculate YLDs, prevalence estimates were multiplied by disability weights. The YLLs were estimated by multiplying age-specific cancer deaths by the reference life expectancy. DALYs were estimated as the sum of YLDs and YLLs. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. Countries were categorized by SDI quintiles to summarize results., Findings: In 2015, there were 17.5 million cancer cases worldwide and 8.7 million deaths. Between 2005 and 2015, cancer cases increased by 33%, with population aging contributing 16%, population growth 13%, and changes in age-specific rates contributing 4%. For men, the most common cancer globally was prostate cancer (1.6 million cases). Tracheal, bronchus, and lung cancer was the leading cause of cancer deaths and DALYs in men (1.2 million deaths and 25.9 million DALYs). For women, the most common cancer was breast cancer (2.4 million cases). Breast cancer was also the leading cause of cancer deaths and DALYs for women (523 000 deaths and 15.1 million DALYs). Overall, cancer caused 208.3 million DALYs worldwide in 2015 for both sexes combined. Between 2005 and 2015, age-standardized incidence rates for all cancers combined increased in 174 of 195 countries or territories. Age-standardized death rates (ASDRs) for all cancers combined decreased within that timeframe in 140 of 195 countries or territories. Countries with an increase in the ASDR due to all cancers were largely located on the African continent. Of all cancers, deaths between 2005 and 2015 decreased significantly for Hodgkin lymphoma (-6.1% [95% uncertainty interval (UI), -10.6% to -1.3%]). The number of deaths also decreased for esophageal cancer, stomach cancer, and chronic myeloid leukemia, although these results were not statistically significant., Conclusion and Relevance: As part of the epidemiological transition, cancer incidence is expected to increase in the future, further straining limited health care resources. Appropriate allocation of resources for cancer prevention, early diagnosis, and curative and palliative care requires detailed knowledge of the local burden of cancer. The GBD 2015 study results demonstrate that progress is possible in the war against cancer. However, the major findings also highlight an unmet need for cancer prevention efforts, including tobacco control, vaccination, and the promotion of physical activity and a healthy diet.

Background: A series of recent reports from large-scale cohort studies involving more than 100,000 subjects reported no or only very small inverse associations between fruit and vegetable intake and overall cancer incidence, despite having sufficient power to do so. To date, however, no such data have been reported for Asian populations., Objective: To provide some indication of the net impact of fruit and vegetable consumption on overall cancer prevention, we examined these associations in a pooled analysis of large-scale cohort studies in Japanese populations., Methods: We analyzed original data from four cohort studies that measured fruit and vegetable consumption using validated questionnaires at baseline. Hazard ratios (HRs) in the individual studies were calculated, with adjustment for a common set of variables, and combined using a random-effects model., Results: During 2,318,927 person-years of follow-up for a total of 191,519 subjects, 17,681 cases of overall cancers were identified. Consumption of fruit or vegetables was not associated with decreased risk of overall cancers: corresponding HRs for the highest versus lowest quartiles of intake for men and women were 1.03 (95% CI, 0.97-1.10; trend p = 1.00) and 1.03 (95% CI, 0.95-1.11; trend p = 0.97), respectively, for fruit and 1.07 (95% CI, 1.01-1.14; trend p = 0.18) and 0.98 (95% CI, 0.91-1.06; trend p = 0.99), respectively, for vegetables, even in analyses stratified by smoking status and alcohol drinking., Conclusions: The results of this pooled analysis do not support inverse associations of fruit and vegetable consumption with overall cancers in the Japanese population., (Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Recent approval of molecular-targeted agents has contributed to improving the therapeutic outcomes of advanced cancer patients. However, they result in unusual adverse events that rarely occur with cytotoxic agents, such as hypertension, hypomagnesemia, and an acne-like rash. Although hypophosphatemia can be induced by various agents, some kinds of molecular-targeted agents are known to induce it. In addition, cancer survivors may be at a risk of hypophosphatemia., Methods: One hundred and seventy patients, who visited the Department of Clinical Oncology at Akita University from 1 April 2014 to 31 August 2016 were enrolled in this study after providing informed consent. Serum inorganic phosphorus levels were examined along with other routine clinical examinations. Correlation between the serum inorganic phosphorus level and other clinical data were also analyzed., Results: Grade ≥2 severe hypophosphatemia (<2.5 mg/dL of phosphorus) was detected in 49.4% of patients, and grade ≥3 (<2.0 mg/dL of phosphorus) was observed in 22.9% patients. These results indicated that the presence of bone metastasis (p < 0.001), history of bone-modifying agents (p < 0.001) and molecular-targeted drugs (p = 0.001), and time from the date of the first visit to the date of minimum serum phosphorus level (p < 0.001) might correlate with hypophosphatemia. Multivariate logistic regression analysis showed that disease duration might be a risk factor (p = 0.0466)., Conclusion: As hypophosphatemia can be induced by various factors in advanced cancer patients, the serum phosphorus level of cancer patients at risk should be cautiously examined.