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Aurélien Belot,1-3 Laurent Remontet,3,4 Bernard Rachet,1 Olivier Dejardin,5,6 Hadrien Charvat,7 Simona Bara,8 Anne-Valérie Guizard,5,9 Laurent Roche,3,4 Guy Launoy,5,6 Nadine Bossard3,4 1Cancer Survival Group, Department of Non-Communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom; 2Non-Communicable Diseases and Trauma Direction, The French Public Health Agency, Saint-Maurice, France; 3Department of Biostatistics and Bioinformatics, Hospices Civils de Lyon, Lyon, France; 4UMR 5558, Biometry and Evolutionary Biology Laboratory, Biostatistics Health Group, CNRS, University Lyon 1, Lyon, France; 5National Institute of Health and Medical Research U1086 ANTICIPE, Caen, France; 6Calvados Digestive Cancer Registry, Centre Hospitalier Universitaire, Caen, France; 7Prevention Division, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan; 8Manche General Cancer Registry, Centre Hospitalier Public du Cotentin, Cherbourg-en-Cotentin, France; 9Calvados General Cancer Registry, Centre François Baclesse, Caen, France Background: Describing the relationship between socioeconomic inequalities and cancer survival is important but methodologically challenging. We propose guidelines for addressing these challenges and illustrate their implementation on French population-based data. Methods: We analyzed 17 cancers. Socioeconomic deprivation was measured by an ecological measure, the European Deprivation Index (EDI). The Excess Mortality Hazard (EMH), ie, the mortality hazard among cancer patients after accounting for other causes of death, was modeled using a flexible parametric model, allowing for nonlinear and/or time-dependent association between the EDI and the EMH. The model included a cluster-specific random effect to deal with the hierarchical structure of the data. Results: We reported the conventional age-standardized net survival (ASNS) and described the changes of the EMH over the time since diagnosis at different levels of deprivation. We illustrated nonlinear and/or time-dependent associations between the EDI and the EMH by plotting the excess hazard ratio according to EDI values at different times after diagnosis. The median excess hazard ratio quantified the general contextual effect. Lip–oral cavity–pharynx cancer in men showed the widest deprivation gap, with 5-year ASNS at 41% and 29% for deprivation quintiles 1 and 5, respectively, and we found a nonlinear association between the EDI and the EMH. The EDI accounted for a substantial part of the general contextual effect on the EMH. The association between the EDI and the EMH was time dependent in stomach and pancreas cancers in men and in cervix cancer. Conclusion: The methodological guidelines proved efficient in describing the way socioeconomic inequalities influence cancer survival. Their use would allow comparisons between different health care systems. Keywords: cancer net survival, socioeconomic inequalities, European Deprivation Index, excess mortality hazard, flexible parametric model

The influence of sugar consumption on the risk of colorectal cancer (CRC) remains controversial. Prospective cohort studies focusing on total and specific types of sugar intake among the Asian population who have different patterns of sugar intake sources than American and European populations are scarce. We intended to examine the association of sugar intake with CRC risk among middle‐aged adults in a Japanese large‐scale population‐based cohort study. The participants (42,405 men and 48,600 women) who were 45–74 years old and answered the questionnaire in 1995–1999 in the Japan Public Health Center‐based Prospective Study were followed up until December 2013. Total sugars, total fructose, and specific types of sugar intake were estimated using a validated 147‐item food frequency questionnaire and divided into quintiles (Q1–Q5). We used Cox proportional hazard regression models adjusted for potential confounders to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During the follow‐up, 2118 CRC cases (1226 men and 892 women) were identified. We did not observe any clear association between all types of sugar intake and an increased risk of CRC. Analyses by tumor sites yielded a positive association of total sugar consumption with rectal cancer in women (1.75 [1.07–2.87] for Q1 vs. Q5; plinear trend = 0.03), but no statistically significant trend was detected among men. Sugar intake was not associated with CRC risk in middle‐aged Japanese adults. However, for rectal cancer, the probability of an increased risk among women with a higher total sugar intake cannot be excluded. [ABSTRACT FROM AUTHOR]

Objectives: The public does not always understand key information conveyed by epidemiologists and statisticians. The purpose of this study was to understand the level of public access to, trust in, and comprehension of, cancer statistics through a population-based survey in Japan., Methods: We used an online research method, requesting online responses to a 15-question questionnaire. The survey was sent to males and females aged 20 years and older, selected by sex, age and prefecture to match the national population proportions shown in the latest census. The final number of valid responses was 10 477. The statistical analyses mainly used χ2 testing., Results: Respondents were not frequently exposed to cancer statistics regardless of sex or age group, nor did they necessarily have confidence in the statistics. The increase of collected information and trust in cancer statistics was aligned with increasing age and cancer exposure. Respondents found Relative Risk and Relative Survival Rate easier to understand and more useful than the Standardized Incidence Ratio. In addition, those with cancer experience, higher income and were elderly gave more accurate responses when asked questions related to cancer incidence and probability of getting cancer., Conclusions: Our respondents showed limited familiarity with cancer statistical indicators. Enhanced awareness of indicators such as infographics and visual tools has the potential to enhance cancer visibility, thereby promoting public prevention and early detection efforts. Educating cancer patients about pertinent indicators can boost their confidence in managing their condition. Conversely, the introduction of indicators unrelated to the public should be discouraged., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

An East Asian-specific variant on aldehyde dehydrogenase 2 ( ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci ( GCKR , KLB , and ADH1B ) in wild-type homozygotes and six ( GCKR , ADH1B , ALDH1B1 , ALDH1A1 , ALDH2 , and GOT2 ) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four ( GCKR , ADH1B , ALDH1A1 , and ALDH2 ) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-related disease risk.

Cancer registry data provide a very important source of information for improving our understanding of the epidemiology of various cancers. In this work, we estimated the 5-year crude probabilities of death from cancer and from other causes for five common cancers, namely stomach, lung, colon-rectum, prostate and breast, in Japan, using population-based registry data. Based on data on 344 676 patients diagnosed with one of these cancers between 2006 and 2008 in 21 prefectures participating in the Monitoring of Cancer Incidence in Japan (MCIJ) and followed-up for at least 5 years, we used a flexible excess hazard model to compute the crude probabilities of death for different combinations of sex, age and stage at diagnosis. For tumours diagnosed at the distant stage, as well as for regional lung tumours, the vast majority of deaths at 5 years in cancer patients were attributable to the disease itself (although this proportion was only around 60% in older prostate cancer patients). For localised and most regional tumours, the impact of other causes of death on the total mortality increased with age at diagnosis, especially for localised breast, colorectal and gastric cancer. By allowing the partition of the mortality experience of cancer patients into a cancer- and an other-cause-specific component, crude probability of death estimates provide insight into how the impact of cancer on mortality might differ among populations with different background mortality risks. This might be useful for informing discussions between clinicians and patients about treatment options., (© 2023 UICC.)

Background: The head and neck cancers (HNCs) incidence differs between Europe and East Asia. Our objective was to determine whether survival of HNC also differs between European and Asian countries., Methods: We used population-based cancer registry data to calculate 5-year relative survival (RS) for the oral cavity, hypopharynx, larynx, nasal cavity, and major salivary gland in Europe, Taiwan, and Japan. We modeled RS with a generalized linear model adjusting for time since diagnosis, sex, age, subsite, and histological grouping. Analyses were performed using federated learning, which enables analyses without sharing sensitive data., Findings: Five-year RS for HNC varied between geographical areas. For each HNC site, Europe had a lower RS than both Japan and Taiwan. HNC subsites and histologies distribution and survival differed between the three areas. Differences between Europe and both Asian countries persisted even after adjustments for all HNC sites but nasal cavity and paranasal sinuses, when comparing Europe and Taiwan., Interpretation: Survival differences can be attributed to different factors including different period of diagnosis, more advanced stage at diagnosis, or different availability/access of treatment. Cancer registries did not have stage and treatment information to further explore the reasons of the observed survival differences. Our analyses have confirmed federated learning as a feasible approach for data analyses that addresses the challenges of data sharing and urge for further collaborative studies including relevant prognostic factors., Competing Interests: LL declares research funds to the institute for clinical studies from Astrazeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann-La Roche ltd, IRX Therapeutics, Medpace, Merck-Serono, MSD, Novartis, Pfizer, Roche, Buran, Alentis; occasional fees for participation as a speaker at conferences/congresses or as a scientific consultant for advisory boards from Astrazeneca, Bayer, MSD, Merck-Serono, AccMed, Neutron Therapeutics, Inc. GGe received grants or contracts from Astra-Zeneca, Janssen, Roche, Health~Holland TKI; KWF Dutch Cancer Society and European Commission. AG received grants or contracts from KWF Dutch Cancer Society and European Commission. AG and GGe have patents assigned to Royal Philips. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Botta, Matsuda, Charvat, Chiang, Lee, van Gestel, Martin, Geleijnse, Cellamare, Bonfarnuzzo, Marcos-Gragera, Guevara, Mousavi, Craig, Rodrigues, Rubió-Casadevall, Licitra, Cavalieri, Resteghini, Gatta, Trama and the RARECAREnet working group.)

Background: Gastric cancer risk can be accurately predicted by measuring the methylation level of a single marker gene in gastric mucosa. However, the mechanism is still uncertain. We hypothesized that the methylation level measured reflects methylation alterations in the entire genome (methylation burden), induced by Helicobacter pylori (H. pylori) infection, and thus cancer risk., Methods: Gastric mucosa of 15 healthy volunteers without H. pylori infection (G1), 98 people with atrophic gastritis (G2), and 133 patients with gastric cancer (G3) after H. pylori eradication were collected. Methylation burden of an individual was obtained by microarray analysis as an inverse of the correlation coefficient between the methylation levels of 265,552 genomic regions in the person's gastric mucosa and those in an entirely healthy mucosa., Results: The methylation burden significantly increased in the order of G1 (n = 4), G2 (n = 18), and G3 (n = 19) and was well correlated with the methylation level of a single marker gene (r = 0.91 for miR124a-3). The average methylation levels of nine driver genes tended to increase according to the risk levels (P = 0.08 between G2 vs G3) and was also correlated with the methylation level of a single marker gene (r = 0.94). Analysis of more samples (14 G1, 97 G2, and 131 G3 samples) yielded significant increases of the average methylation levels between risk groups., Conclusions: The methylation level of a single marker gene reflects the methylation burden, which includes driver gene methylation, and thus accurately predicts cancer risk., (© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

In the presence of competing causes of event occurrence (e.g., death), the interest might not only be in the overall survival but also in the so-called net survival, that is, the hypothetical survival that would be observed if the disease under study were the only possible cause of death. Net survival estimation is commonly based on the excess hazard approach in which the hazard rate of individuals is assumed to be the sum of a disease-specific and expected hazard rate, supposed to be correctly approximated by the mortality rates obtained from general population life tables. However, this assumption might not be realistic if the study participants are not comparable with the general population. Also, the hierarchical structure of the data can induces a correlation between the outcomes of individuals coming from the same clusters (e.g., hospital, registry). We proposed an excess hazard model that corrects simultaneously for these two sources of bias, instead of dealing with them independently as before. We assessed the performance of this new model and compared it with three similar models, using extensive simulation study, as well as an application to breast cancer data from a multicenter clinical trial. The new model performed better than the others in terms of bias, root mean square error, and empirical coverage rate. The proposed approach might be useful to account simultaneously for the hierarchical structure of the data and the non-comparability bias in studies such as long-term multicenter clinical trials, when there is interest in the estimation of net survival., (© 2023 The Authors. Biometrical Journal published by Wiley-VCH GmbH.)

Background: Population-based cancer registry (PBCR) data provide crucial information for evaluating the effectiveness of cancer services and reflect prospects for cure by estimating population-based cancer survival. This study provides long-term trends in survival among patients diagnosed with cancer in the Barretos region (São Paulo State, Brazil)., Methods: In this population-based study, we estimated the one- and five-year age-standardized net survival rates of 13,246 patients diagnosed with 24 different cancer types in Barretos region between 2000 and 2018. The results were presented by sex, time since diagnosis, disease stage, and period of diagnosis., Results: Marked differences in the one- and five-year age-standardized net survival rates were observed across the cancer sites. Pancreatic cancer had the lowest 5-year net survival (5.5 %, 95 %CI: 2.9-9.4) followed by oesophageal cancer (5.6 %, 95 %CI: 3.0-9.4), while prostate cancer ranked the best (92.1 %, 95 %CI: 87.8-94.9), followed by thyroid cancer (87.4 %, 95 %CI: 69.9-95.1) and female breast cancer (78.3 %, 95 %CI: 74.5-81.6). The survival rates differed substantially according to sex and clinical stage. Comparing the first (2000-2005) and last (2012-2018) periods, cancer survival improved, especially for thyroid, leukemia, and pharyngeal cancers, with differences of 34.4 %, 29.0 %, and 28.7 %, respectively., Conclusion: To our knowledge, this is the first study to evaluate long-term cancer survival in the Barretos region, showing an overall improvement over the last two decades. Survival varied by site, indicating the need for multiple cancer control actions in the future with a lower burden of cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests related to the study “Cancer survival in the northwestern of São Paulo state, Brazil: a population-based study”., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Over the last 50 years, occupational exposure to carcinogenic agents has been widely regulated in France., Objective: Report population-attributable fraction (PAF) and number of attributable cancer cases linked to occupational exposure in France based on an updated method to estimate lifetime occupational exposure prevalence., Methods: Population-level prevalence of lifetime exposure to ten carcinogenic agents (asbestos, benzene, chromium VI, diesel engine exhaust, formaldehyde, nickel compounds, polycyclic aromatic hydrocarbons, silica dust, trichloroethylene, wood dust) and two occupational circumstances (painters and rubber industry workers) were estimated using the French Census linked with MATGÉNÉ job-exposure matrices and French occupational surveys. PAF and number of attributable cancer cases were calculated using the estimated prevalence, relative risks from systematic review and national estimates of cancer incidence in 2017., Results: The lifetime occupational exposure prevalences were much higher in men than in women ranging from 0.2% (workers in the rubber industry) to 10.2% in men (silica), and from 0.10% (benzene, PAH and workers in the rubber industry) to 5.7% in women (formaldehyde). In total, 4,818 cancer cases (men: 4,223; women: 595) were attributable to the ten studied carcinogens and two occupational circumstances, representing 5.2% of cases among the studied cancer sites (M: 7.0%; W: 1.9%). In both sexes, mesothelioma (M: 689 cases; W: 160) and lung cancer (M: 3,032; W: 308) were the largest cancer sites impacted by the studied occupational agents and circumstances., Significance: A moderate proportion of the cancer cases in France is linked to carcinogens in occupational settings. Our method provides more precise estimates of attributable cancer taking into account evolution of exposure to occupational agents by sex, age and time. This methodology can be easily replicated using cross-sectional occupational data to aid priority making and implementation of prevention strategies in the workplace., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: We evaluated the association between total soy, soy product (natto, miso and tofu) and isoflavone intake and incident disabling dementia in a Japanese population., Methods: We conducted a population-based prospective study in 18,991 men and 22,456 women. Intake of soy products and isoflavone was calculated using a validated food frequency questionnaire when participants were 45-74 years old (1995 and 1998). Incident disabling dementia was defined by the daily living disability status related to dementia in the long-term care insurance program of Japan from 2006 to 2016. Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) of disabling dementia were calculated by quintiles of total soy, individual soy product and isoflavone intake, using Cox proportional hazard regression models., Results: Total soy product intake was not associated with disabling dementia risk in both men and women. By individual soy products, natto intake was marginally inversely associated with disabling dementia in women (trend P = 0.050). When we stratified by age, this inverse association was clearer in women aged under 60 years (multivariate HR for the highest versus lowest quintile was 0.78, 95% CI 0.59-1.04, trend P = 0.020 for those aged under 60 years and 0.90, 95% CI 0.77-1.05, trend P = 0.23 for those aged 60 years and older, respectively). Any soy product or isoflavone intake was not associated with disabling dementia risk in men., Conclusions: Although total soy product intake was not associated with disabling dementia risk, natto intake may contribute to reducing the risk of disabling dementia in women, especially in those aged under 60 years., (© 2022. The Author(s).)

Background: Reducing socioeconomic inequalities in cancer is a priority for the public health agenda. A systematic assessment and benchmarking of socioeconomic inequalities in cancer across many countries and over time in Europe is not yet available., Methods: Census-linked, whole-of-population cancer-specific mortality data by socioeconomic position, as measured by education level, and sex were collected, harmonized, analysed, and compared across 18 countries during 1990-2015, in adults aged 40-79. We computed absolute and relative educational inequalities; temporal trends using estimated-annual-percentage-changes; the share of cancer mortality linked to educational inequalities., Findings: Everywhere in Europe, lower-educated individuals have higher mortality rates for nearly all cancer-types relative to their more highly-educated counterparts, particularly for tobacco/infection-related cancers [relative risk of lung cancer mortality for lower- versus higher-educated = 2.4 (95% confidence intervals: 2.1-2.8) among men; = 1.8 (95% confidence intervals: 1.5-2.1) among women]. However, the magnitude of inequalities varies greatly by country and over time, predominantly due to differences in cancer mortality among lower-educated groups, as for many cancer-types higher-educated have more similar (and lower) rates, irrespective of the country. Inequalities were generally greater in Baltic/Central/East-Europe and smaller in South-Europe, although among women large and rising inequalities were found in North-Europe (relative risk of all cancer mortality for lower- versus higher-educated ≥1.4 in Denmark, Norway, Sweden, Finland and the England/Wales). Among men, rate differences (per 100,000 person-years) in total-cancer mortality for lower-vs-higher-educated groups ranged from 110 (Sweden) to 559 (Czech Republic); among women from approximately null (Slovenia, Italy, Spain) to 176 (Denmark). Lung cancer was the largest contributor to inequalities in total-cancer mortality (between-country range: men, 29-61%; women, 10-56%). 32% of cancer deaths in men and 16% in women (but up to 46% and 24%, respectively in Baltic/Central/East-Europe) were associated with educational inequalities., Interpretation: Cancer mortality in Europe is largely driven by levels and trends of cancer mortality rates in lower-education groups. Even Nordic-countries, with a long-established tradition of equitable welfare and social justice policies, witness increases in cancer inequalities among women. These results call for a systematic measurement, monitoring and action upon the remarkable socioeconomic inequalities in cancer existing in Europe., Funding: This study was done as part of the LIFEPATH project, which has received financial support from the European Commission (Horizon 2020 grant number 633666), and the DEMETRIQ project, which received support from the European Commission (grant numbers FP7-CP-FP and 278511). SV and WN were supported by the French Institut National du Cancer (INCa) (Grant number 2018-116). PM was supported by the Academy of Finland (#308247, # 345219) and the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement No 101019329). The work by Mall Leinsalu was supported by the Estonian Research Council (grant PRG722)., Competing Interests: We declare no competing interests., (© 2022 Published by Elsevier Ltd.)

We aimed to explore the underlying reasons that estimates of overdiagnosis vary across and within low-dose computed tomography (LDCT) lung cancer screening trials. We conducted a systematic review to identify estimates of overdiagnosis from randomised controlled trials of LDCT screening. We then analysed the association of Ps (the excess incidence of lung cancer as a proportion of screen-detected cases) with postscreening follow-up time using a linear random effects meta-regression model. Separately, we analysed annual Ps estimates from the US National Lung Screening Trial (NLST) and German Lung Cancer Screening Intervention Trial (LUSI) using exponential decay models with asymptotes. We conducted stratified analyses to investigate participant characteristics associated with Ps using the extended follow-up data from NLST. Among 12 overdiagnosis estimates from 8 trials, the postscreening follow-up ranged from 3.8 to 9.3 years, and Ps ranged from -27.0% (ITALUNG, 8.3 years follow-up) to 67.2% (DLCST, 5.0 years follow-up). Across trials, 39.1% of the variation in Ps was explained by postscreening follow-up time. The annual changes in Ps were -3.5% and -3.9% in the NLST and LUSI trials, respectively. Ps was predicted to plateau at 2.2% for NLST and 9.2% for LUSI with hypothetical infinite follow-up. In NLST, Ps increased with age from -14.9% (55-59 years) to 21.7% (70-74 years), and time trends in Ps varied by histological type. The findings suggest that differences in postscreening follow-up time partially explain variation in overdiagnosis estimates across lung cancer screening trials. Estimates of overdiagnosis should be interpreted in the context of postscreening follow-up and population characteristics., (© 2022 The World Health Organization. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Epstein-Barr virus (EBV) is one of the risk factors of nasopharyngeal carcinoma (NPC), and understanding the modifiable risk factors of EBV activation is crucial in the prevention of NPC. In this study, we aimed to investigate the association between solid fuel use and EBV seropositivity in a high-risk area of NPC. Our study was based on the baseline findings from an ongoing population-based prospective cohort in Sihui county in Southern China. We explored the association between current use of solid fuel in cooking and EBV seropositivity, and NPC-related EBV activation, using logistic regression models. Stratification analyses were further conducted to assess potential effect modifiers. We also examined the impact of frequency and duration of solid fuel use, and switch in fuel types, on EBV seropositivity among ever users. Of the 12,579 participants included in our analysis, 4088 (32.5%) were EBV seropositive and 421 (3.3%) were high risk for NPC-related EBV activation. Solid fuel use was associated with a higher risk of EBV seropositivity and NPC-related EBV activation, with odds ratios (ORs) of 1.33 (95%CI: 1.01, 1.76) and 1.81 (95%CI: 1.03, 3.18), respectively. Higher risk of EBV seropositivity was observed for those who did not use ventilation apparatus and those who consumed salted food. Among ever users, OR was highest for participants with more than 40 years of solid fuel exposure (1.17, 95%CI: 1.00-1.37) and who have been constantly using solid fuel (1.30, 95%CI: 0.96-1.75). We did not find a statistically significant impact of cooking frequency on EBV seropositivity. The identification of solid fuel as a risk factor for EBV activation is of great value for understanding the etiology of NPC. Our findings also have important public health implications given the fact that a third of the global population still lack access to clean cooking, especially in low resource settings., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Body mass index (BMI) and cardiometabolic comorbidities such as cardiovascular disease and type 2 diabetes have been studied as negative prognostic factors in cancer survival, but possible dependencies in the mechanisms underlying these associations remain largely unexplored. We analysed these associations in colorectal and breast cancer patients., Methods: Based on repeated BMI assessments of cancer-free participants from four European countries in the European Prospective Investigation into Cancer and nutrition (EPIC) study, individual BMI-trajectories reflecting predicted mean BMI between ages 20 to 50 years were estimated using a growth curve model. Participants with incident colorectal or breast cancer after the age of 50 years were included in the survival analysis to study the prognostic effect of mean BMI and cardiometabolic diseases (CMD) prior to cancer. CMD were defined as one or more chronic conditions among stroke, myocardial infarction, and type 2 diabetes. Hazard ratios (HRs) and confidence intervals (CIs) of mean BMI and CMD were derived using multivariable-adjusted Cox proportional hazard regression for mean BMI and CMD separately and both exposures combined, in subgroups of localised and advanced disease., Results: In the total cohort of 159,045 participants, there were 1,045 and 1,620 eligible patients of colorectal and breast cancer. In colorectal cancer patients, a higher BMI (by 1 kg/m2) was associated with a 6% increase in risk of death (95% CI of HR: 1.02-1.10). The HR for CMD was 1.25 (95% CI: 0.97-1.61). The associations for both exposures were stronger in patients with localised colorectal cancer. In breast cancer patients, a higher BMI was associated with a 4% increase in risk of death (95% CI: 1.00-1.08). CMDs were associated with a 46% increase in risk of death (95% CI: 1.01-2.09). The estimates and CIs for BMI remained similar after adjustment for CMD and vice versa., Conclusions: Our results suggest that cumulative exposure to higher BMI during early to mid-adulthood was associated with poorer survival in patients with breast and colorectal cancer, independent of CMD prior to cancer diagnosis. The association between a CMD diagnosis prior to cancer and survival in patients with breast and colorectal cancer was independent of BMI., (© 2022. The Author(s).)

Background: Many epidemiological studies have reported the association between exposure to particulate matter and mortality, but long-term prospective studies from Asian populations are sparse. Furthermore, associations at low levels of air pollution are not well clarified. Here, we evaluated associations between long-term exposure to particulate matter <2.5 µg/m 3 (PM 2.5 ) and mortality in a Japanese cohort with a relatively low exposure level., Methods: The Japan Public Health Center-based Prospective Study (JPHC Study) is a prospective cohort study of men and women aged 40-69 years in 1990 who were followed up through 2013 for mortality. In this cohort of 87,385 subjects who did not move residence during follow-up, average PM 2.5 levels from 1998 to 2013 by linkage with 1-km 2 grids of PM 2.5 concentration were assigned to the residential addresses of all participants. To avoid exposure misclassification, we additionally evaluated the association between 5-year (1998-2002) cumulative exposure level and mortality during the follow-up period from 2003 to 2013 in 79,078 subjects. Cox proportional hazards models were used to calculate the association of long-term exposure to PM 2.5 on mortality, with adjustment for several individual confounding factors., Results: Average PM 2.5 was 11.6 µg/m 3 . Average PM 2.5 exposure was not associated with all-cause mortality or cancer and respiratory disease mortality. However, average PM 2.5 was positively associated with mortality from cardiovascular disease (hazard ratio (HR) of 1.23 (95%CI=1.08-1.40) per 1-µg/m 3 increase; in particular, HR in mortality from cerebrovascular disease was 1.34 (95%CI=1.11-1.61) per 1-µg/m 3 increase. Additionally, these results using cumulative 5-year PM 2.5 data were similar to those using average PM 2.5 over 15 years., Conclusions: We found evidence for a positive association between PM 2.5 exposure and mortality from cardiovascular disease in a Japanese population, even in an area with relatively low-level air pollution., (© 2022. The Author(s).)

Importance: The associations of daily total physical activity and total moderate to vigorous physical activity (MVPA) with dementia are still unclear., Objective: To investigate the association between daily total physical activity and subsequent risk of disabling dementia in large-scale, extended follow-up prospective study., Design, Setting, and Participants: This prospective cohort study used data from questionnaires collected between 2000 and 2003 from 8 areas from the Japan Public Health Center-based Prospective Disabling Dementia Study. Participants included adults aged 50 to 79 years in with available follow-up data on disabling dementia. Data analysis was performed from February 1, 2019, to July 31, 2021., Exposures: Daily total physical activity, total MVPA, and leisure-time MVPA., Main Outcomes and Measures: The main outcome was incidence of disabling dementia during the dementia ascertainment period between 2006 and 2016, based on the national long-term care insurance system. Risks of dementia in association with daily total physical activity, total MVPA, and leisure time MVPA were calculated using multivariable adjusted hazard ratios (aHRs)., Results: Among 43 896 participants (mean [SD] age, 61.0 [7.5] years; 23 659 [53.9%] women), 5010 participants were newly diagnosed with disabling dementia during a mean (SD) of 9.5 (2.8) years in the dementia ascertainment period. In the highest daily total physical activity group, compared with the lowest activity group, risk of dementia was lower in men (aHR, 0.75 [95% CI, 0.66-0.85]; P for trend < .001) and women (aHR, 0.75 [95% CI, 0.67-0.84]; P for trend < .001). Similar inverse associations were observed in men and women for total MVPA (men: aHR, 0.74 [95% CI, 0.65-0.84]; P for trend < .001; women: aHR, 0.74 [95% CI, 0.66-0.83]; P for trend < .001) and leisure-time MVPA (men: aHR, 0.59 [95% CI, 0.53-0.67]; P for trend < .001; women: aHR, 0.70 [95% CI, 0.63-0.78]; P for trend < .001). However, these inverse associations disappeared when participants diagnosed with disabling dementia within 7 years of the starting point were excluded in men (aHR, 0.93 [95%CI, 0.77-1.12]) and within 8 years were excluded in women (aHR, 0.86 [95%CI, 0.71-1.04]). The association remained significant among men in the highest vs lowest group of leisure-time MVPA, after excluding participants diagnosed within the first 9 years (aHR, 0.72 [95% CI, 0.56-0.92]; P for trend = .004)., Conclusions and Relevance: This cohort study examined associations of daily total physical activity and total MVPA with risk of disabling dementia. The findings suggest that a high level of leisure-time MVPA was associated with decreased risk of disabling dementia in men.

Background: Here, we explore the association between excess weight during early to mid-adulthood and survival in patients diagnosed with breast and colorectal cancer, using a pooled analysis of five cohort studies and study participants from 11 countries., Methods: Participant-level body mass index (BMI) trajectories were estimated by fitting a growth curve model using over 2 million repeated BMI measurements from close to 600,000 cohort participants. Cumulative measures of excess weight were derived. Data from over 23,000 patients with breast and colorectal cancer were subsequently analyzed using time-to-event models for death with the date of diagnosis as start of follow-up. Study-specific results were combined through a random effect meta-analysis., Results: We found a significant dose-response relationship ( P trend = 0.013) between the average BMI during early and mid-adulthood and death from breast cancer, with a pooled HR of 1.31 (1.07-1.60) and the time to death shortened by 16% for average BMI above 25 kg/m 2 compared with average BMI less than or equal to 22.5 kg/m 2 , respectively. Similar results were found for categories of cumulative time spent with excess weight. There was no association between excess body fatness during early to mid-adulthood and death in patients with colorectal cancer., Conclusions: Excess body fatness during early to mid-adulthood is associated not only with an increased risk of developing cancer, but also with a lower survival in patients with breast cancer., Impact: Our results emphasize the importance of public health policies aimed at reducing overweight during adulthood and inform future studies on the relationship between excess weight and cancer outcomes., (©2021 American Association for Cancer Research.)

Background: Previous prospective studies of associations between circulating inflammation-related molecules and pancreatic cancer risk have included limited numbers of markers., Methods: We conducted a case-cohort study nested within the Japan Public Health Center-based Prospective Study Cohort II. We selected a random subcohort ( n = 774) from a total of 23,335 participants aged 40 to 69 years who returned a questionnaire and provided blood samples at baseline. During the follow-up period from 1993 to 2010, we identified 111 newly diagnosed pancreatic cancer cases, including one case within the subcohort. Plasma concentrations of 62 inflammatory markers of chemokines, cytokines, and growth factors were measured by a Luminex fluorescent bead-based assay. Cox regression models were applied to estimate HR and 95% confidence intervals (CI) for pancreatic cancer risk for quartiles of marker levels adjusted for potential confounders., Results: The HR (95% CI) for the highest versus the lowest category of C-C motif ligand chemokine 8/monocyte chemoattractant protein 2 (CCL8/MCP2) was 2.03 (1.05-3.93; P trend = 0.048). After we corrected for multiple comparisons, none of the examined biomarkers were associated with pancreatic cancer risk at P -value <0.05., Conclusions: We found no significant associations between 62 inflammatory markers and pancreatic cancer risk., Impact: The suggestive association with circulating levels of leukocyte recruiting cytokine CCL8/MCP2 may warrant further investigation., (©2021 American Association for Cancer Research.)