[Is "tobacco harm reduction" possible? Other countries' experiences and perspectives, and how they could inform tobacco control in Japan].

　"Tobacco harm reduction" is defined as a method to minimize harm and risk of death and disease without eliminating tobacco and nicotine use. In Japan, where heated tobacco products (HTPs) are prevalent, the tobacco industry is progressively endorsing the concept of "tobacco harm reduction." Therefore, stakeholders in tobacco control must urgently share perspectives and experiences surrounding this issue.　This discussion paper aimed to propose four requirements for effectively implementing "tobacco harm reduction" as a public health measure: (1) disease risk reduction, (2) cigarette smoking cessation, (3) no additional public health concerns, and (4) regulatory authorities held by health agencies, and compile information on them regarding nicotine-containing electronic cigarettes (e-cigarettes) and HTPs. Another aim was to summarize policies related to "tobacco harm reduction" adopted by an international organization (World Health Organization (WHO) and health authorities in foreign countries (the United States of America (USA), the United Kingdom (UK), Australia, Italy, and the Republic of Korea) to explore the implications of these requirements on Japan's approach. Regarding the first three requirements, scientific evidence indicated that e-cigarettes offers some level of risk reduction and can assist with cigarette smoking cessation. The potential uptake of e-cigarettes among youth and their possibility to serve as a gateway to combusted cigarette use is a concern, though a definitive causal link is yet to be established between the uptake of e-cigarette in youth and the subsequent use of different tobacco products. There is insufficient scientific evidence for any of the three requirements for HTPs. Regarding the official policies, WHO took the position that the same regulations should be applied to all tobacco products. Only the UK and USA officially established a health system based on the concept of "tobacco harm reduction"; even in Italy and the Republic of Korea, where HTPs are relatively widespread, health authorities denied any risk reduction by introducing HTPs. The UK officially adopted a smoking cessation policy with e-cigarettes. The USA established a modified risk tobacco product system under federal legislation enacted in 2009, whereas of June 2023, no HTP or e-cigarettes were recognized as explicitly reducing health risk. Regarding the fourth requirement, the UK and USA institutionalized "tobacco harm reduction" under health authorities' regulation independent of the tobacco industry. The introduction of a tobacco harm reduction policy in Japan should be considered only in line with health authorities' regulation and implementation of comprehensive tobacco control measures independent of the tobacco industry.

Exposure to pesticides and risk of Hodgkin lymphoma in an international consortium of agricultural cohorts (AGRICOH).

PURPOSE: Some pesticides may increase the risk of certain lymphoid malignancies, but few studies have examined Hodgkin lymphoma (HL). In this exploratory study, we examined associations between agricultural use of 22 individual active ingredients and 13 chemical groups and HL incidence. METHODS: We used data from three agricultural cohorts participating in the AGRICOH consortium: the French Agriculture and Cancer Cohort (2005-2009), Cancer in the Norwegian Agricultural Population (1993-2011), and the US Agricultural Health Study (1993-2011). Lifetime pesticide use was estimated from crop-exposure matrices or self-report. Cohort-specific covariate-adjusted overall and age-specific (< 40 or ≥ 40 years) hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression and combined using random effects meta-analysis. RESULTS: Among 316 270 farmers (75% male) accumulating 3 574 815 person-years at risk, 91 incident cases of HL occurred. We did not observe statistically significant associations for any of the active ingredients or chemical groups studied. The highest risks of HL overall were observed for the pyrethroids deltamethrin (meta-HR = 1.86, 95% CI 0.76-4.52) and esfenvalerate (1.86, 0.78-4.43), and inverse associations of similar magnitude were observed for parathion and glyphosate. Risk of HL at ≥ 40 years of age was highest for ever-use of dicamba (2.04, 0.93-4.50) and lowest for glyphosate (0.46, 0.20-1.07). CONCLUSION: We report the largest prospective investigation of these associations. Nonetheless, low statistical power, a mixture of histological subtypes and a lack of information on tumour EBV status complicate the interpretability of the results. Most HL cases occurred at older ages, thus we could not explore associations with adolescent or young adult HL. Furthermore, estimates may be attenuated due to non-differential exposure misclassification. Future work should aim to extend follow-up and refine both exposure and outcome classification.

Prevalence of subclinical lung cancer detected at autopsy: a systematic review.

BACKGROUND: Lung cancer screening in high-risk populations with low-dose computed tomography is supported by international associations and recommendations. Overdiagnosis is considered a risk of screening with associated harms. The aim of this paper is to determine the prevalence of subclinical lung cancer diagnosed post-mortem to better understand the reservoir of subclinical lung cancer. METHODS: We searched EMBASE, PubMed, and MEDLINE databases from inception until March 2022 with no language restrictions. We considered all studies with ≥100 autopsies in adults. Two reviewers independently assessed eligibility of studies, extracted data, and assessed risk of bias of included studies. We performed a meta-analysis using a random-effects model for prevalence of subclinical lung cancer diagnosed post-mortem with sensitivity and subgroup analyses. RESULTS: A total of 13 studies with 16 730 autopsies were included. Pooled prevalence was 0.4% (95% CI 0.20 to 0.82%, I2 = 84%, tau2 = 1.19, low certainty evidence,16 730 autopsies). We performed a sensitivity analysis excluding studies which did not specify exclusion of children in their cohort, with a pooled prevalence of subclinical lung cancer of 0.87% (95% CI 0.48 to 1.57%, I2 = 71%, tau2 = 0.38, 6998 autopsies, 8 studies). CONCLUSIONS: This is the first published systematic review to evaluate the prevalence of post-mortem subclinical lung cancer. Compared to autopsy systematic reviews in breast, prostate and thyroid cancers, the pooled prevalence is lower in lung cancer for subclinical cancer. This result should be interpreted with caution due to the included studies risk of bias and heterogeneity, with further high-quality studies required in target screening populations.

Practical Implications of the Update to the 2015 Japan Standard Population: Mortality Archive From 1950 to 2020 in Japan.

BACKGROUND: The 2015 Japan Standard Population (JSP) was established in response to changes in the age structure. However, the effects of major updates, especially the recategorization of older age groups, for interpreting various health metrics have not been clarified. METHODS: Population data were collected and estimated for older age categories (85-89, 90-94, and ≥95 years). Data on the number of deaths were also collected from the Vital Statistics. We recalculated the all-cause and leading cause-specific age-standardized mortality rate (ASMR) using the 2015 JSP by the direct standardization method for data from 1950 to 2020. We compared ASMRs calculated using the 2015 JSP with those calculated using the 1985 JSP. Pearson's correlation coefficients were used to evaluate the consistency of mortality trends between the 2015 and 1985 JSPs. RESULTS: The absolute all-cause ASMRs calculated using the 2015 JSP were 2.22-3.00 times higher than those calculated using the 1985 JSP. The ASMR ratios increased gradually over time. While trends in all-cause and cause-specific ASMRs calculated using the 2015 JSP and 1985 JSP were generally highly correlated (Pearson's correlation coefficient [r] = 0.993 for all-cause), correlations were relatively low for malignant neoplasms (r = 0.720 for men and r = 0.581 for women) and pneumonia/bronchitis (r = 0.543 for men and r = 0.559 for women) due to non-monotonous trends over time and fluctuations in earlier time periods. CONCLUSION: The effect of introducing the new JSP for interpreting trends in all-cause mortality was considered minimal. However, caution is needed when interpreting trends in some cause-specific mortality rates.

Response to Toshihide Tsuda, Yumiko Miyano and Eiji Yamamoto [1].

BACKGROUND: Using a toolkit approach, Tsuda et al. critiqued work carried out by or in collaboration with the International Agency for Research on Cancer (IARC/WHO), including the IARC technical publication No. 46 on "Thyroid health monitoring after nuclear accidents" (TM-NUC), the project on nuclear emergency situations and improvement on medical and health surveillance (SHAMISEN), and the IARC-led work on global thyroid cancer incidence patterns as per IARC core mandate. MAIN BODY: We respond on the criticism of the recommendations of the IARC technical publication No. 46, and of global thyroid cancer incidence evaluation. CONCLUSION: After nuclear accidents, overdiagnosis can still happen and must be included in informed decision making when providing a system of optimal help for cases of radiation-induced thyroid cancer, to minimize harm to people by helping them avoid diagnostics and treatment they may not need.

[Geographic information in National Cancer Registry data: Overseas examples and challenges in Japan].

Worldwide, research based on geographic information of official statistical data, including cancer registries, is utilized for cancer control and public health policies. The National Cancer Registry of Japan was launched in 2016, making it possible to use data on cancer incidence systematically. Given the nature of this comprehensive survey, the usefulness of the National Cancer Registry would be further enhanced when it is utilized at small-regional levels, such as in municipalities or even smaller geographical units. It is essential to maintain a balance between privacy protection and data usability. Currently, the national and prefectural councils determine the availability of the data from the National Cancer Registry at the small-regional level on an individual application basis. Under this framework, use of the data is often restricted or declined. This paper showcases three model countries where geographic information obtained from cancer registry data are widely utilized: the United States, Canada, and the United Kingdom. It further discusses measures to ensure that data are effectively used, without compromising data privacy. In the three countries, data-providing systems have been established to compile the necessary data from the cancer registry and other linked databases, in accordance with the purpose of use. The relationships between healthcare access and various outcomes are elaborately examined at the small-regional level. In Japan, similar utilization of data has not been fully implemented, and there remain many hurdles to the application of the data use. For the National Cancer Registry to promote research and further enhance cancer control, it is necessary to establish a system that enables effective and safe utilization of the data from the National Cancer Registry, including linkage with other data and on-site use.

Projecting the impact of implementation of WHO MPOWER measures on smoking prevalence and mortality in Japan.

OBJECTIVE: This study aimed to quantify the long-term impact of implementing the WHO Framework Convention on Tobacco Control (FCTC) compliant tobacco control measures, MPOWER, on smoking prevalence and mortality in men and women aged ≥20 years in Japan. DESIGN: A Stock-and-Flow simulation model was used to project smoking prevalence and mortality from 2018 to 2050 under eight different scenarios: (1) maintaining the 2018 status quo, (2) implementation of smoke-free policies, (3) tobacco use cessation programmes, (4-5) health warning about the dangers of tobacco (labels, mass media), (6) enforcement of tobacco advertising bans or (7) tobacco taxation at the highest recommended level and (8) all these interventions combined. RESULTS: Under the status quo, the smoking prevalence in Japan will decrease from 29.6% to 15.5% in men and 8.3% to 4.7% in women by 2050. Full implementation of MPOWER will accelerate this trend, dropping the prevalence to 10.6% in men and 3.2% in women, and save nearly a quarter million deaths by 2050. This reduction implies that Japan will only attain the current national target of 12% overall smoking prevalence in 2033, 8 years earlier than it would with the status quo (in 2041), a significant delay from the national government's 2022 deadline. CONCLUSIONS: To bring forward the elimination of tobacco smoking and substantially reduce smoking-related deaths, the government of Japan should fulfil its commitment to the FCTC and adopt stringent tobacco control measures delineated by MPOWER and beyond.

Parental occupational exposures in wood-related jobs and risk of testicular germ cell tumours in offspring in NORD-TEST a registry-based case-control study in Finland, Norway, and Sweden.

OBJECTIVE: We assessed the association between parental prenatal exposures in wood-related jobs and risk of testicular germ cell tumours (TGCT) in offspring. METHODS: NORD-TEST, a registry-based case-control study in Sweden, Finland and Norway, included 8112 TGCT cases diagnosed at ages 14-49 years between 1978 and 2012 with no history of prior cancer, and up to four controls matched to each case on year and country of birth. Parents of cases and controls were identified via linkages with the population registries and their occupational information was retrieved from censuses. The Nordic Occupational Cancer Study Job-Exposure Matrix was used to assign occupational exposures to each parent. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Maternal wood-related job was not associated with the risk of TGCT in offspring (OR 1.08, CI 0.55-2.14), while paternal wood-related job was associated with a decreased risk of TGCT in offspring (OR 0.85, CI 0.75-0.96). None of the specific wood-related jobs, such as upholsterers, sawyers, or construction carpenters, were significantly associated with a risk of TGCT. Only exception was observed in a sensitivity analysis which showed an increased risk in the small group of sons of fathers working as 'cabinetmakers and joiners' the year before conception (OR of 2.06, CI 1.00-4.25). CONCLUSION: This large-scale NORD-TEST analysis provided no evidence of an association between parental prenatal exposures in wood-related jobs and TGCT in sons.

Geospatial barriers to healthcare access for breast cancer diagnosis in sub-Saharan African settings: The African Breast Cancer-Disparities in Outcomes Cohort Study.

We examined the geospatial dimension of delays to diagnosis of breast cancer in a prospective study of 1541 women newly diagnosed in the African Breast Cancer-Disparities in Outcomes (ABC-DO) Study. Women were recruited at cancer treatment facilities in Namibia, Nigeria, Uganda and Zambia. The baseline interview included information used to generate the geospatial features: urban/rural residence, travel mode to treatment facility and straight-line distances from home to first-care provider and to diagnostic/treatment facility, categorized into country/ethnicity (population)-specific quartiles. These factors were investigated in relation to delay in diagnosis (≥3 months since first symptom) and late stage at diagnosis (TNM: III, IV) using logistic regression, adjusted for population group and sociodemographic characteristics. The median (interquartile range) distances to first provider and diagnostic and treatment facilities were 5 (1-37), 17 (3-105) and 62 (5-289) km, respectively. The majority had a delay in diagnosis (74%) and diagnosis at late stage (64%). Distance to first provider was not associated with delay in diagnosis or late stage at diagnosis. Rural residence was associated with delay, but the association did not persist after adjustment for sociodemographic characteristics. Distance to the diagnostic/treatment facility was associated with delay (highest vs lowest quartile: odds ratio (OR) = 1.56, 95% confidence interval (CI) = 1.08-2.27) and late stage (overall: OR = 1.47, CI = 1.05-2.06; without Nigerian hospitals where mostly local residents were treated: OR = 1.73, CI = 1.18-2.54). These findings underscore the need for measures addressing the geospatial barriers to early diagnosis in sub-Saharan African settings, including providing transport or travel allowance and decentralizing diagnostic services.

Body mass index at age 18 years and recent body mass index in relation to risk of breast cancer overall and ER/PR/HER2-defined subtypes in white women and African-American women: a pooled analysis.

BACKGROUND: Although it has been well-documented that obesity is associated with decreased risk of premenopausal breast cancer and increased risk of postmenopausal breast cancer, it is unclear whether these associations differ among breast cancer subtypes defined by the tumor protein expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). METHODS: We evaluated the associations of body mass index (BMI) at age 18 years and recent BMI in relation to risk of breast cancer overall and ER/PR/HER2-defined subtypes, in 6320 women (3934 case-patient participants, 2386 control participants) aged 35-64 years, who participated in one of three population-based case-control studies. We estimated multivariable-adjusted odd ratios (ORs) and corresponding 95% confidence intervals (CIs) using polychotomous unconditional logistic regression methods for case-control comparisons in premenopausal women and postmenopausal women. RESULTS: BMI at age 18 years was inversely associated with risk of breast cancer, particularly among premenopausal women (≥ 25 vs. < 20 kg/m2, OR = 0.72, 95% CI = 0.53-0.96; per 5 kg/m2 increase, OR = 0.83, 95% CI = 0.73-0.95). This inverse association did not differ across ER/PR/HER2-defined subtypes or by race (white women, African-American women). Recent BMI was not associated with risk of premenopausal breast cancer after adjustment for BMI at age 18 years; nevertheless, the analysis for the joint effects of BMI at age 18 years and recent BMI showed that premenopausal women in the highest categories of the two BMI measures (≥ 25 kg/m2 at age 18 years and ≥ 30 kg/m2 for recent BMI) had 46% lower risk of breast cancer than premenopausal women in the lowest categories of the two BMI measures (< 20 kg/m2 at age 18 years and < 25 kg/m2 for recent BMI; OR = 0.54, 95% CI = 0.38-0.78). Neither measure of BMI was statistically significantly associated with risk of postmenopausal breast cancer. CONCLUSION: Our findings indicate that high BMI near the end of adolescence decreases risk of all ER/PR/HER2-defined subtypes of premenopausal breast cancer and also suggest that this benefit could be maximized among premenopausal women who consistently have high BMI during their premenopausal years.

Reproductive factors and the risk of triple-negative breast cancer in white women and African-American women: a pooled analysis.

BACKGROUND: Early age at menarche, nulliparity, late age at first completed pregnancy, and never having breastfed, are established breast cancer risk factors. However, among breast cancer subtypes, it remains unclear whether all of these are risk factors for triple-negative breast cancer (TNBC). METHODS: We evaluated the associations of these reproductive factors with TNBC, in 2658 patients with breast cancer (including 554 with TNBC) and 2448 controls aged 20-64 years, who participated in one of the three population-based case-control studies: the Women's Contraceptive and Reproductive Experiences Study, the Women's Breast Carcinoma in situ Study, or the Women's Learning the Influence of Family and Environment Study. We used multivariable polychotomous unconditional logistic regression methods to conduct case-control comparisons among breast cancer subtypes defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression status. RESULTS: TNBC risk decreased with increasing duration of breastfeeding (P trend = 0.006), but age at menarche, age at first completed pregnancy, and nulliparity were not associated with risk of TNBC. Parous women who breastfed for at least one year had a 31% lower risk of TNBC than parous women who had never breastfed (odds ratio, OR = 0.69; 95% confidence interval, CI = 0.50-0.96). The association between breastfeeding and risk of TNBC was modified by age and race. Parous African-American women aged 20-44 years who breastfed for 6 months or longer had an 82% lower risk of TNBC than their counterparts who had never breastfed (OR = 0.18, 95% CI = 0.07-0.46). CONCLUSIONS: Our data indicate that breastfeeding decreases the risk of TNBC, especially for younger African-American women.

Recreational physical activity and risk of triple negative breast cancer in the California Teachers Study.

BACKGROUND: Evidence has accumulated showing that recreational physical activity reduces breast cancer risk. However, it is unclear whether risk reduction pertains to specific receptor-defined subtypes. Moreover, few studies have examined whether changes in the amount of recreational physical activity during adulthood influence breast cancer risk. METHODS: A total of 108,907 women, ages 22 to 79 years with no history of breast cancer when joining the California Teachers Study in 1995-1996, completed a baseline questionnaire and were eligible for the study. Through 2012, 5882 women were diagnosed with invasive breast cancer. Breast cancer subtypes were defined by the expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Multivariable Cox proportional hazards models provided adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) for breast cancer overall and ER/PR/HER2-defined subtypes associated with long-term (from high school through age 54 or age at cohort entry, whichever was younger) and baseline (during 3 years prior to baseline) recreational physical activity. Among women who also completed a follow-up questionnaire at 10 years after baseline in 2005-2008 (54,686 women, 1406 with invasive breast cancer), risk associated with changes in the amount of recreational physical activity from baseline to the 10-year follow-up (during 3 years prior to the 10-year follow-up) was determined. RESULTS: Both long-term and baseline strenuous recreational physical activity were inversely associated with risk of invasive breast cancer (P trend ≤0.03). The observed associations were mainly confined to women with triple negative breast cancer (TNBC, ER-/PR-/HER2-, P trend ≤0.02) or luminal A-like subtype (ER+ or PR+ plus HER2-) who were former users of menopausal hormone therapy at baseline (P trend = 0.02, P homogeneity of trends ≤0.03). Moreover, women who consistently engaged in the highest level (≥3.51 h/wk/y) of strenuous recreational physical activity between baseline and 10-year follow-up had the lowest risk of breast cancer (HR = 0.71, 95 % CI = 0.52-0.98) when compared to those who were consistently low (≤0.50 h/wk/y). CONCLUSIONS: Strenuous recreational physical activity is associated with lower breast cancer risk, especially TNBC. The benefit may be maximized by consistently engaging in high-intensity recreational physical activity during adulthood.

Longitudinal trajectory of sexual functioning after hematopoietic cell transplantation: impact of chronic graft-versus-host disease and total body irradiation.

This prospective study described the trajectory of sexual well-being from before hematopoietic cell transplantation (HCT) to 3 years after in 131 allogeneic and 146 autologous HCT recipients using Derogatis Interview for Sexual Function and Derogatis Global Sexual Satisfaction Index. Sixty-one percent of men and 37% of women were sexually active pre-HCT; the prevalence declined to 51% (P = .01) in men and increased to 48% (P = .02) in women at 3 years post-HCT. After HCT, sexual satisfaction declined in both sexes (P < .001). All sexual function domains were worse in women compared with men (P ≤ .001). Orgasm (P = .002) and drive/relationship (P < .001) declined in men, but sexual cognition/fantasy (P = .01) and sexual behavior/experience (P = .01) improved in women. Older age negatively impacted sexual function post-HCT in both sexes (P < .01). Chronic graft-versus-host disease was associated with lower sexual cognition/fantasy (P = .003) and orgasm (P = .006) in men and sexual arousal (P = .05) and sexual satisfaction (P = .005) in women. All male sexual function domains declined after total body irradiation (P < .05). This study identifies vulnerable subpopulations that could benefit from interventional strategies to improve sexual well-being.

Risk factors for self-reported arm lymphedema among female breast cancer survivors: a prospective cohort study.

INTRODUCTION: Lymphedema is a potentially debilitating condition that occurs among breast cancer survivors. This study examines the incidence of self-reported lymphedema, timing of lymphedema onset, and associations between sociodemographic, clinical and lifestyle factors and lymphedema risk across racial-ethnic groups using data from a multicenter, multiethnic prospective cohort study of breast cancer survivors, the Health, Eating, Activity and Lifestyle Study. METHODS: A total of 666 women diagnosed with breast cancer staged as in situ, localized or regional disease at ages 35 to 64 years were recruited through the Surveillance, Epidemiology, and End Results registries in New Mexico (non-Hispanic white and Hispanic white), Los Angeles County (black), and Western Washington (non-Hispanic white) and followed for a median of 10.2 years. We evaluated sociodemographic factors, breast cancer- and treatment-related factors, comorbidities, body mass index (BMI), hormonal factors, and lifestyle factors in relation to self-reported lymphedema by fitting Cox proportional hazards models, estimating hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Over the follow-up period, 190 women (29%) reported lymphedema. The median time from breast cancer diagnosis to onset of lymphedema was 10.5 months (range: 0.5 to 134.9 months). Factors independently associated with lymphedema were total/modified radical mastectomy (versus partial/less than total mastectomy; HR = 1.37, 95% CI: 1.01 to 1.85), chemotherapy (versus no chemotherapy; HR = 1.48, 95% CI: 1.09 to 2.02), no lymph nodes removed (versus ≥10 lymph nodes removed; HR = 0.17, 95% CI: 0.08 to 0.33), pre-diagnostic BMI ≥30 kg/m2 (versus BMI <25 kg/m2; HR = 1.59, 95% CI: 1.09 to 2.31), and hypertension (versus no hypertension; HR = 1.49, 95% CI: 1.06 to 2.10). After adjusting for demographics and breast cancer- and treatment-related factors, no significant difference in lymphedema risk was observed across racial/ethnic groups. Analyses stratified by race/ethnicity showed that hypertension and chemotherapy were lymphedema risk factors only for black women. CONCLUSIONS: Breast cancer patients who have undergone extensive surgery or extensive lymph node dissection, or who have a higher BMI should be closely monitored for detection and treatment of lymphedema. Further studies are needed to understand the roles of chemotherapy and hypertension in the development of lymphedema.

Educational inequalities in all-cause and cause-specific mortality in Japan: national census-linked mortality data for 2010-15.

BACKGROUND: Due to the lack of a national mortality inequality monitoring framework, the overall picture in Japan remains unclear. Here, we investigated educational inequalities in mortality and their cause-specific contribution in Japan. METHOD: Data were obtained by linking the 2010 Japanese population census and death records between 1 October 2010 and 30 September 2015. We included 7 984 451 Japanese people aged 30-79 years who had a unique 'matching key' generated by sex, birth year/month, address (municipality), marital status and age of spouse (9.9% of the total census population). We computed population-weighted all-cause and cause-specific age-standardized mortality rates (ASMRs) by education level. In addition, we calculated the slope index of inequality (SII), relative index inequality (RII) by education level, and population attributable fraction (PAF) referenced with the highest education (e.g. university graduation). RESULTS: Individuals with less education had higher all-cause and cause-specific ASMRs than highly educated individuals. All-cause SII (per 100 000 person-years) values were 433 (95% CI: 410-457) for men and 235 (95% CI: 217-252) for women. RII values were 1.48 (95% CI: 1.45-1.51) for men and 1.47 (95% CI: 1.43-1.51) for women. Estimated PAFs, excess premature deaths caused by educational inequalities, were 11.6% for men and 16.3% for women, respectively. Cerebrovascular diseases, ischaemic heart diseases and lung cancer were the major contributors to mortality inequalities for both sexes. CONCLUSIONS: This first census-based comprehensive report on cause-specific educational mortality inequalities suggested that differences in unfavourable health risk factors by educational background might be associated with these inequalities in Japan.

Geospatial disparities in survival of patients with breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes cohort (ABC-DO): a prospective cohort study.

BACKGROUND: There is an urgent need to improve breast cancer survival in sub-Saharan Africa. Geospatial barriers delay diagnosis and treatment, but their effect on survival in these settings is not well understood. We examined geospatial disparities in 4-year survival in the African Breast Cancer-Disparities in Outcomes cohort. METHODS: In this prospective cohort study, women (aged ≥18 years) newly diagnosed with breast cancer were recruited from eight hospitals in Namibia, Nigeria, South Africa, Uganda, and Zambia. They reported sociodemographic information in interviewer-administered questionnaires, and their clinical and treatment data were collected from medical records. Vital status was ascertained by contacting participants or their next of kin every 3 months. The primary outcome was all-cause mortality in relation to rural versus urban residence, straight-line distance, and modelled travel time to hospital, analysed using restricted mean survival time, Cox proportional hazards, and flexible parametric survival models. FINDINGS: 2228 women with breast cancer were recruited between Sept 8, 2014, and Dec 31, 2017. 127 were excluded from analysis (58 had potentially recurrent cancer, had previously received treatment, or had no follow-up; 14 from minority ethnic groups with small sample sizes; and 55 with missing geocoded home addresses). Among the 2101 women included in analysis, 928 (44%) lived in a rural area. 1042 patients had died within 4 years of diagnosis; 4-year survival was 39% (95% CI 36-42) in women in rural areas versus 49% (46-52) in urban areas (unadjusted hazard ratio [HR] 1·24 [95% CI 1·09-1·40]). Among the 734 women living more than 1 h from the hospital, the crude 4-year survival was 37% (95% CI 32-42) in women in rural areas versus 54% (46-62) in women in urban areas (HR 1·35 [95% CI 1·07-1·71] after adjustment for age, stage, and treatment status). Among women in rural areas, mortality rates increased with distance (adjusted HR per 50 km 1·04, 1·01-1·07) and travel time (adjusted HR per h 1·06, 1·02-1·10). Among women with early-stage breast cancer receiving treatment, women in rural areas had a strong survival disadvantage (overall HR 1·54, 1·14-2·07 adjusted for age and stage; >1 h distance adjusted HR 2·14, 1·21-3·78). INTERPRETATION: Geospatial barriers reduce survival of patients with breast cancer in sub-Saharan Africa. Specific attention is needed to support patients with early-stage breast cancer living in rural areas far from cancer treatment facilities. FUNDING: US National Institutes of Health (National Cancer Institute), Susan G Komen for the Cure, and the International Agency for Research on Cancer.

Mapping recommendations towards an Asian Code Against Cancer (ACAC) as part of the World Code Against Cancer Framework: an Asian National Cancer Centers Alliance (ANCCA) initiative.

This paper outlines the process undertaken by Asian National Cancer Centers Alliance (ANCCA) members in working towards an Asian Code Against Cancer (ACAC). The process involves: (i) identification of the criteria for selecting the existing set of national recommendations for ACAC (ii) compilation of existing national codes or recommendations on cancer prevention (iii) reviewing the scientific evidence on cancer risk factors in Asia and (iv) establishment of one or more ACAC under the World Code Against Cancer Framework. A matrix of national codes or key recommendations against cancer in ANCCA member countries is presented. These include taking actions to prevent or control tobacco consumption, obesity, unhealthy diet, physical inactivity, alcohol consumption, exposure to occupational and environmental toxins; and to promote breastfeeding, vaccination against infectious agents and cancer screening. ANCCA will continue to serve as a supportive platform for collaboration, development, and advocacy of an ACAC jointly with the International Agency for Research on Cancer/World Health Organization (IARC/WHO).

Toxicity of bevacizumab in combination with chemotherapy in older patients.

BACKGROUND: Bevacizumab leads to improved survival for patients with metastatic colorectal cancer (CRC) or non-small cell lung cancer (NSCLC) when added to chemotherapy. Little is known about factors associated with receipt of bevacizumab, or whether bevacizamab is associated with increased toxicity when added to chemotherapy. PATIENTS AND METHODS: We conducted a prospective study of patients aged ≥65 years, which evaluated the association between geriatric assessment (GA) metrics and chemotherapy toxicity. We examined differences in characteristics and outcomes of patients with CRC and NSCLC cancers who received bevacizumab with chemotherapy versus chemotherapy alone. RESULTS: From a total of 207 patients, 27 (13%) received bevacizumab plus chemotherapy and 180 (87%) received chemotherapy alone. Groups were similar in sociodemographic and cancer characteristics. There were no baseline differences in GA domains except that patients with heart disease were less likely to receive bevacizumab (4% vs. 26%, p = .01). Seventy-eight percent of patients who had bevacizumab had grade 3-5 toxicity compared to only 57% who received chemotherapy alone (p = .06). Patients receiving bevacizumab were more likely to develop grade 3 hypertension than those who received chemotherapy alone (15% vs. 2%, p < .01). In multivariable analysis, factors associated with grade 3 or more toxicity included: bevacizumab (OR: 2.86, p = .04), CRC (OR: 2.54, p < .01), and baseline anemia (OR: 2.58, p = .03). CONCLUSION: Heart disease was more common in those who did not receive bevacizumab. Older patients who receive bevacizumab with chemotherapy have a higher odds of developing a grade 3-5 toxicity compared with those who receive chemotherapy alone.