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Background: Tobacco smoking is still frequent in Italy and a major cause of cancer globally. We estimated the burden of smoking-related cancer in Italy., Methods: To calculate the population attributable fraction (PAF), we adopted a counterfactual scenario for which all individuals never smoked. The PAF of current and former smoking and second-hand smoke (SHS) was estimated for cancers associated with these habits according to the International Agency for Research on Cancer. Relative risk estimates and prevalence of exposure were derived from large-scale studies and national surveys, respectively. A 20-year latency period between exposure and cancer was considered. Cancer incidence data for 2020 and mortality data for 2017 were obtained from the Italian Association of Cancer Registries., Results: Tobacco smoking caused, in men and women respectively, 90.0 % and 58.3 % of lung; 67.8 % and 53.5 % of pharyngeal; 47.0 % and 32.2 % of bladder; 45.9 % and 31.7 % of oral; 36.6 % and 23.6 % of esophageal; 23.0 % and 14.0 % of pancreatic cancer and lower percentages of cancers at other sites. Tobacco smoking accounted for 23.9 % and 7.7 % of new cancer cases in 2020, and 32.1 % and 11.3 % of cancer deaths in 2017 in men and women, respectively, corresponding to 17.3 % of cases and 24.5 % of cancer deaths overall. The PAF of lung cancer due to SHS in never smoking women married with smokers was 13.0 %., Conclusions: Tobacco smoking is a primary cause of cancer in Italy in both sexes. Tobacco control policies are warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Numerous studies have reported lower overall cancer mortality rates among immigrants compared to native populations. However, limited information exists regarding cancer mortality among immigrants based on specific birth countries and cancer types. We used population-based registries and followed 10 million individuals aged 20 years or older in Sweden between 1992 and 2016. The Cox proportional hazard model was used to explore the disparities in cancer mortality by country of birth and cancer type, stratified by gender. Age-standardized mortality rates were also computed using the world standard population. Hazard ratio (HR) of all-site cancer was slightly lower among immigrants (males: HR m  = 0.97: 95% confidence interval: 0.95, 0.98; females: HR f  = 0.93: 0.91, 0.94) than Swedish-born population. However, the immigrants showed higher mortality for infection-related cancers, including liver (HR f  = 1.10: 1.01, 1.19; HR m  = 1.10: 1.02, 1.17), stomach (HR f  = 1.39: 1.31, 1.49; HR m  = 1.33: 1.26, 1.41) cancers, and tobacco-related cancers, including lung (HR m  = 1.44: 1.40, 1.49), and laryngeal cancers (HR m  = 1.47: 1.24, 1.75). The HR of mesothelioma was also significantly higher in immigrants (HR f  = 1.44: 1.10, 1.90). Mortality from lung cancer was specifically higher in men from Nordic (HR m  = 1.41: 1.27, 1.55) and non-Nordic Europe (HR m  = 1.49: 1.43, 1.55) countries and lower in Asian (HR m  = 0.78: 0.66, 0.93) and South American men (HR m  = 0.70: 0.57, 0.87). In conclusion, there are large variations in cancer mortality by country of birth, and cancer type and require regular surveillance. Our detailed analyses lead to some novel findings such as excess mortality rate of mesothelioma and laryngeal cancers in Immigrants in Sweden. A targeted cancer prevention program among immigrants in Sweden is needed., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Associations between mineral intake and mortality in non-Western countries have not been studied adequately. This study evaluated these associations in the Golestan Cohort Study, featuring a Middle Eastern population. The mineral intake was estimated from the baseline food frequency questionnaire, adjusted by using the nutrient density method, and divided into quintiles. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the mortality. We analyzed 41,863 subjects with a mean age of 51.46 ± 8.73 years at the baseline. During 578,694 person-years of follow-up (median: 14.1 Years), 7217 deaths were recorded. Dietary calcium intake was inversely associated with the all-cause mortality (HR Q5 vs. Q1 = 0.91, 95%CI = 0.85-0.99). We observed significant associations between calcium (HR Q5 vs. Q1 = 0.82, 95% CI = 0.73-0.93), copper (HR Q5 vs. Q1 = 1.11, 95% CI = 0.99-1.26), and selenium intake (HR Q5 vs. Q1 = 1.14, 95% CI = 1.01-1.29) and CVD mortality. Dietary phosphorus (HR Q5 vs. Q1 = 0.81, 95%CI = 0.69-0.96) and copper intake (HR Q5 vs. Q1 = 0.84, 95%CI = 0.71-0.99) were inversely associated with cancer mortality. In this study within a Middle Eastern population, a higher dietary intake of calcium exhibited an inverse association with all-cause mortality. Furthermore, nuanced associations were observed in the cause-specific mortality, suggesting potential avenues for dietary interventions and emphasizing the importance of considering dietary factors in public health strategies.

Background & Aims: Overweight and obesity are associated with multiple cancers. We quantified the burden of cancer attributable to overweight and obesity in Italy., Methods: We estimated sex- and cancer site-specific population attributable fractions (PAFs) combining relative risks (from recent meta-analyses) with national obesity prevalence data (from a large sample survey conducted in 2005, to account for a 15-year lag period). Using nationwide mortality statistics and cancer registries data, we estimated the number of cancer cases and deaths attributable to overweight and obesity in Italy in 2020, based on the counterfactual scenario of a body mass index < 25 kg/m 2 ., Results: 3.6% of cancers in men and 4.0% in women in Italy were attributable to overweight and obesity, corresponding, respectively, to over 6900 and 7200 diagnoses in 2020. Attributable deaths were over 3600 in men and 2700 in women. PAFs (attributable cases) of overweight and obesity in men and women were, respectively, 38.1% (215 cases) and 21.8% (49 cases) for esophageal adenocarcinoma, 19.1% (1715 cases) and 14.5% (585 cases) for liver, 18.7% (1692 cases) and 16.7% (747 cases) for kidney, 13.7% (938 cases) and 10.1% (749 cases) for pancreatic, and 10.2% (2389 cases) and 3.4% (690 cases) for colorectal cancers. In women, PAFs were 22.3% (1859 cases) for endometrial and 5.7% (2556 cases) for post-menopausal breast cancer., Conclusions: The cancer burden associated with overweight and obesity in Italy is considerable, but smaller compared to other high income countries, likely because of the lower prevalence of overweight and obesity in the Italian population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This study provides a nationwide representative quantification of the impact of educational inequalities on cancer mortality in Italy., Methods: The study is based on prevalence data and mortality rate ratios according to levels of education obtained from the Italian 2011 census cohort, including >35 million individuals aged 30-74. We estimated the population attributable fraction (PAF) and the number of cancer deaths associated with low education (below university degree) in Italy by sex., Results: PAFs for low levels of education were 29.1% among men and 13.3% among women, corresponding to 22,271 cancer deaths associated with low education in men and 7456 in women in 2019. PAFs by cancer site in men were: 53.0% for upper aerodigestive tract (UADT), 44.6% for liver, 41.3% for stomach, 41.3% for lung, 37.0% for bladder, 18.5% for colorectal, 9.8% for prostate and 9.1% for pancreatic cancers. PAFs in women were: 44.5% for cervical, 36.1% for UADT, 34.9% for stomach and 13.9% for colorectal cancers. The cancer sites with the highest number of deaths associated with low education were lung among men (7902/22,271, 35.5%) and colorectum among women (780/7456, 10.5%)., Conclusions: About a quarter of cancer deaths in 2019 in Italy may be prevented by reducing the socioeconomic determinants that contribute to educational disparities in cancer mortality., (© The Author(s) 2023. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To compare mortality rates in World Trade Center (WTC)-exposed Fire Department of the City of New York (FDNY) firefighters with rates in similarly healthy, non-WTC-exposed/non-FDNY firefighters, and compare mortality in each firefighter cohort with the general population., Methods: 10 786 male WTC-exposed FDNY firefighters and 8813 male non-WTC-exposed firefighters from other urban fire departments who were employed on 11 September 2001 were included in the analyses. Only WTC-exposed firefighters received health monitoring via the WTC Health Programme (WTCHP). Follow-up began 11 September 2001 and ended at the earlier of death date or 31 December 2016. Death data were obtained from the National Death Index and demographics from the fire departments. We estimated standardised mortality ratios (SMRs) in each firefighter cohort versus US males using demographic-specific US mortality rates. Poisson regression models estimated relative rates (RRs) of all-cause and cause-specific mortality in WTC-exposed versus non-WTC-exposed firefighters, controlling for age and race., Results: Between 11 September 2001 and 31 December 2016, there were 261 deaths among WTC-exposed firefighters and 605 among non-WTC-exposed. Both cohorts had reduced all-cause mortality compared with US males (SMR (95% CI)=0.30 (0.26 to 0.34) and 0.60 (0.55 to 0.65) in WTC-exposed and non-WTC-exposed, respectively). WTC-exposed firefighters also had lower rates of all-cause mortality (RR=0.54, 95% CI=0.49 to 0.59) and cancer-specific, cardiovascular-specific and respiratory disease-specific mortality compared with non-WTC-exposed firefighters., Conclusion: Both firefighter cohorts had lower than expected all-cause mortality. Fifteen years post 11 September 2001, mortality was lower in WTC-exposed versus non-WTC-exposed firefighters. Lower mortality in the WTC-exposed suggests not just a healthy worker effect, but additional factors such as greater access to free health monitoring and treatment that they receive via the WTCHP., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The implementation of primary and secondary preventive strategies is based on the evidence generated by cancer epidemiology, where the identification of risk factors and the description of their prevalence are fundamental to derive estimates on the burden of cancer from different etiologies, typically expressed as the population attributable fraction, which corresponds to the proportion of a cancer that may be prevented by controlling a given risk factor. However, even when cancer finds its etiology in modifiable factors, its prevention through the control of those factors is not always feasible, or it remains suboptimal despite the possibility of reducing the burden. We reviewed selected associations between modifiable risk factors and cancer, including tobacco smoking, occupational exposures, infections, air pollution, alcohol, and diet and obesity, and illustrated examples of both successes and failures in cancer control, underlying how current understanding of the avoidable causes of cancer is incomplete.

Objectives: To provide an evidence-based, comprehensive assessment of the current burden of infection-related cancers in Italy., Methods: We calculated the proportion of cancers attributable to infectious agents (Helicobacter pylori [Hp]; hepatitis B virus [HBV] and hepatitis C virus [HCV]; human papillomavirus [HPV]; human herpesvirus-8 [HHV8]; Epstein-Barr virus [EBV]; and human immunodeficiency virus [HIV]) to estimate the burden of infection-related cancer incidence (2020) and mortality (2017). Data on the prevalence of infections were derived from cross-sectional surveys of the Italian population, and relative risks from meta-analyses and large-scale studies. Attributable fractions were calculated based on the counterfactual scenario of a lack of infection., Results: We estimated that 7.6% of total cancer deaths in 2017 were attributable to infections, with a higher proportion in men (8.1%) than in women (6.9%). The corresponding figures for incident cases were 6.5%, 6.9% and 6.1%. Hp was the first cause of infection-related cancer deaths (3.3% of the total), followed by HCV (1.8%), HIV (1.1%), HBV (0.9%), HPV, EBV and HHV8 (each ≤0.7%). Regarding incidence, 2.4% of the new cancer cases were due to Hp, 1.3% due to HCV, 1.2% due to HIV, 1.0% due to HPV, 0.6% due to HBV and <0.5% due to EBV and HHV8., Conclusions: Our estimate of 7.6% of cancer deaths and 6.9% of incident cases that were attributable to infections in Italy is higher than those estimated in other developed countries. Hp is the major cause of infection-related cancer in Italy. Prevention, screening and treatment policies are needed to control these cancers, which are largely avoidable., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: A decrease in cancer mortality has been reported in the USA, possibly due to decreased incidence, downstaging and improved survival. The aim of the present study is to estimate the contribution of these factors on the trend in cancer mortality., Methods: Data on incidence, mortality, stage at diagnosis, and overall and stage-specific survival for six common digestive and respiratory cancers (esophagus, stomach, colorectal, liver, pancreas and lung) during 2009-2013 in the USA from the surveillance, epidemiology and end results (SEER) program, was analyzed using generalized linear models separately among men and women., Results: Our study showed a decrease in mortality for esophageal (-0.09/100 000/year and -0.03/100 000/year), stomach (-0.11/100 000/year and -0.05/100 000/year), colorectal (-0.45/100 000/year and -0.29/100 000/year) and lung cancer (-1.89/100 000/year in men and -0.78/100 000/year in women) in men and women, respectively: for all of them, except lung cancer in women, there was a decrease in the incidence of comparable or greater magnitude; stage distribution and survival also contributed to the decrease in mortality for lung and colorectal cancer. Mortality from pancreatic cancer was stable: an increase in incidence was counterbalanced by an improvement in survival. Mortality from liver cancer increased, driven by an increase in mortality that was not offset by favorable trends in stage distribution and survival., Conclusions: Trends in mortality were primarily affected by changes in incidence; an increase in the proportion of local stage at diagnosis and improved survival, although evident for some cancers, played a lesser role in mortality trends., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Many health services, including cancer care, have been affected by the COVID-19 epidemic. This study aimed at providing a systematic review of the impact of the epidemic on cancer diagnostic tests and diagnosis worldwide. In our systematic review and meta-analysis, databases such as Pubmed, Proquest and Scopus were searched comprehensively for articles published between January 1st, 2020 and December 12th, 2021. Observational studies and articles that reported data from single clinics and population registries comparing the number of cancer diagnostic tests and/or diagnosis performed before and during the pandemic, were included. Two pairs of independent reviewers extracted data from the selected studies. The weighted average of the percentage variation was calculated and compared between pandemic and pre-pandemic periods. Stratified analysis was performed by geographic area, time interval and study setting. The review was registered on PROSPERO (ID: CRD42022314314). The review comprised 61 articles, whose results referred to the period January-October 2020. We found an overall decrease of - 37.3% for diagnostic tests and - 27.0% for cancer diagnosis during the pandemic. For both outcomes we identified a U-shaped temporal trend, with an almost complete recovery for the number of cancer diagnosis after May 2020. We also analyzed differences by geographic area and screening setting. We provided a summary estimate of the decrease in cancer diagnosis and diagnostic tests, during the first phase of the COVID-19 pandemic. The delay in cancer diagnosis could lead to an increase in the number of avoidable cancer deaths. Further research is needed to assess the impact of the pandemic measures on cancer treatment and mortality., (© 2022. The Author(s).)

In the last years, the discussion about the role of chance in the causation of cancer has generated much scientific and public debate. The concept that chance, or "bad luck", as responsible for a majority of the variation of cancer incidence, may be misleading, possibly causing an underestimation of the role played by known risk factors. In this commentary we discuss how host and external factors interact with chance in cancer causation in different ways, and provide examples of situations where chance appears to play only a minor role on cancer onset.

Given the limited studies and controversial results on association between dietary acid load and mortality from CVD and cancers, we aimed to investigate this association in a large population cohort study in Middle East, with a wide range of dietary acid load. The study was conducted on the platform of the Golestan Cohort Study (GCS), which enrolled 50 045 participants in 2004-2008. Dietary intake was assessed using a validated FFQ. Dietary potential renal acid load (PRAL) score was calculated from nutrient intake. Death and its causes were identified and confirmed by two or three physicians. Cox proportional hazards regression was used to estimate hazard ratio (HR) and 95 % CI for total and cause-specific mortalities. Then, the associations were modelled using restricted cubic splines. PRAL range was -57·36 to +53·81 mEq/d for men and -76·70 to +49·08 for women. During 555 142 person-years of follow-up, we documented 6830 deaths, including 3070 cardiovascular deaths, 1502 cancer deaths and 2258 deaths from other causes. For overall deaths, in final model after adjustment for confounders, participants in the first and fifth quintiles of PRAL had a higher risk of mortality compared with the second quintile of PRAL (HR: 1·08; 95 % CI1·01, 1·16 and HR: 1·07; 95 % CI 1·01, 1·15, respectively); P for trend < 0·05). Participants in the first and fifth quintiles of PRAL had a 12 % higher risk of CVD mortality compared with the Q2 of PRAL (HR: 1·12; 95 % CI 1·01-1·25 and HR: 1·12; 95 % CI 1·01, 1·26, respectively; P for trend < 0·05). We found that all-cause and CVD mortality rates were higher in the lowest and highest PRAL values, in an approximately U-shaped relation ( P -values for the overall association and the non-linear association of energy-adjusted PRAL with total mortality were < 0·001 and < 0·001, and with CVD mortality were 0·008 and 0·003, respectively). Our results highlight unfavourable associations of high acidity and alkalinity of diet with the increased total and CVD mortality risk. It may be important to consider a balanced acid-base diet as a protective strategy to prevent pre-mature death, especially from CVD.

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.)

We estimated cancer mortality statistics for the current year in seven major Latin American countries, with a focus on colorectal cancer. We retrieved official death certification data and population figures from the World Health Organization and the Pan American Health Organization databases. We analysed mortality from all neoplasms combined and for selected cancer sites. We estimated numbers of deaths and age-standardized mortality rates for the year 2021 using a logarithmic Poisson count data joinpoint model. Total cancer mortality is predicted to decline in all countries considered for both sexes, with the exception of Argentinian women. The lowest total mortality rates were predicted in Mexico (65.4/100 000 men and 62.3 in women), the highest ones were in Cuba (133.3/100 000 men and 91.0 in women). Stomach cancer rates have been decreasing since 1970 in all countries; colorectal cancer started to decline over recent calendar periods. Rates for this cancer were unfavourable in the youngest age group. Lung cancer trends declined in males and remained comparatively low in all countries except Cuba. In Cuba, lung cancer rates in women overtook those for breast. Mortality from cancers of the breast, (cervix) uterus, ovary, prostate and bladder, as well as leukemia mostly showed favourable trends. A marked variability in rates across Latin American countries persists, and rates were relatively high for stomach, uterus, prostate and lung cancers, as compared to Europe and North America, suggesting the need to improve preventive strategies. Colorectal cancer mortality was relatively low in Latin America, except in Argentina, and short-term predictions remain moderately favourable., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

In recent years there has been a growth in the role of prevention in controlling the disease burden. Increasing efforts have been conveyed in the screening implementation and public health policies, and the spreading knowledge on risk factors reflects on major attention to health checks. Despite this, lifestyle changes are difficult to be adopted and the adherence to current public health services like screening and vaccinations remains suboptimal. Additionally, the prevalence and outcome of different chronic diseases and cancers is burdened by social disparities. P4 [predictive, preventive, personalized, participatory] medicine is the conceptualization of a new health care model, based on multidimensional data and machine-learning algorithms in order to develop public health intervention and monitoring the health status of the population with focus on wellbeing and healthy ageing. Each of the characteristics of P4 medicine is relevant to occupational medicine, and indeed the P4 approach appears to be particularly relevant to this discipline. In this review, we discuss the potential applications of P4 to occupational medicine, showing examples of its introduction on workplaces and hypothesizing its further implementation at the occupational level.

Background: Since the beginning of the SARS-CoV-2 pandemic, cancer patients affected by COVID-19 have been reported to experience poor prognosis; however, a detailed quantification of the effect of cancer on outcome of unvaccinated COVID-19 patients has not been performed., Methods: To carry out a systematic review of the studies comparing the outcome of unvaccinated COVID-19 patients with and without cancer, a search string was devised which was used to identify relevant publications in PubMed up to December 31, 2020. We selected three outcomes: mortality, access to ICU, and COVID-19 severity or hospitalization. We considered results for all cancers combined as well as for specific cancers. We conducted random-effects meta-analyses of the results, overall and after stratification by region. We also performed sensitivity analyses according to quality score and assessed publication bias., Results: For all cancer combined, the pooled odds ratio (OR) for mortality was 2.32 (95% confidence interval [CI] 1.82-2.94, I 2 for heterogeneity 90.1%, 24 studies), that for ICU admission was 2.39 (95% CI 1.90-3.02, I 2 0.0%, 5 studies), that for disease severity or hospitalization was 2.08 (95% CI 1.60-2.72, I 2 92.1%, 15 studies). The pooled mortality OR for hematologic neoplasms was 2.14 (95% CI 1.87-2.44, I 2 20.8%, 8 studies). Data were insufficient to perform a meta-analysis for other cancers. In the mortality meta-analysis for all cancers, the pooled OR was higher for studies conducted in Asia than studies conducted in Europe or North America. There was no evidence of publication bias., Conclusions: Our meta-analysis indicates a twofold increased risk of adverse outcomes (mortality, ICU admission, and severity of COVID-19) in unvaccinated COVID-19 patients with cancer compared to COVID-19 patients without cancer. These results should be compared with studies conducted in vaccinated patients; nonetheless, they argue for special effort to prevent SARS-CoV-2 infection in patients with cancer., Funding: No external funding was obtained., Competing Interests: GD, GV, FT, MA, PB No competing interests declared, (© 2022, Di Felice et al.)

Background: World Trade Center (WTC)-exposed responders may be eligible to receive no-cost medical monitoring and treatment for certified conditions, including cancer. The survival of responders with cancer has not previously been investigated., Methods: This study compared the estimated relative survival of WTC-exposed responders who developed cancer while enrolled in two WTC medical monitoring and treatment programs in New York City (WTC-MMTP responders) and WTC-exposed responders not enrolled (WTC-non-MMTP responders) to non-responders from New York State (NYS-non-responders), all restricted to the 11-southernmost NYS counties, where most responders resided. Parametric survival models estimated cancer-specific and all-cause mortality. Follow-up ended at death or on December 31, 2016., Results: From January 1, 2005 to December 31, 2016, there were 2,037 cancer cases and 303 deaths (248 cancer-related deaths) among WTC-MMTP responders, 564 cancer cases, and 143 deaths (106 cancer-related deaths) among WTC-non-MMTP responders, and 574,075 cancer cases and 224,040 deaths (158,645 cancer-related deaths) among the NYS-non-responder population. Comparing WTC-MMTP responders with NYS-non-responders, the cancer-specific mortality hazard ratio (HR) was 0.72 (95% confidence interval [CI] = 0.64-0.82), and all-cause mortality HR was 0.64 (95% CI = 0.58-0.72). The cancer-specific HR was 0.94 (95% CI = 0.78-1.14), and all-cause mortality HR was 0.93 (95% CI = 0.79-1.10) comparing WTC-non-MMTP responders to the NYS-non-responder population., Conclusions: WTC-MMTP responders had lower mortality compared with NYS-non-responders, after controlling for demographic factors and temporal trends. There may be survival benefits from no-out-of-pocket-cost medical care which could have important implications for healthcare policy, however, other occupational and socioeconomic factors could have contributed to some of the observed survival advantage., (© 2021 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals LLC.)

Background: Marked reductions in childhood cancer mortality occurred over the last decades in high-income countries and, to a lesser degree, in middle-income countries. This study aimed to monitor mortality trends in the Americas and Australasia, focusing on areas showing unsatisfactory trends., Methods: Age-standardized mortality rates per 100,000 children (aged 0-14 years) from 1990 to 2017 (or the last available calendar year) were computed for all neoplasms and 8 leading childhood cancers in countries from the Americas and Australasia, using data from the World Health Organization database. A joinpoint regression was used to identify changes in slope of mortality trends for all neoplasms, leukemia, and neoplasms of the central nervous system (CNS) for major countries., Results: Over the last decades, childhood cancer mortality continued to decrease by approximately 2% to 3% per year in Australasian countries (ie, Japan, Korea, and Australia), by approximately 1.5% to 2% in North America and Chile, and 1% in Argentina. Other Latin American countries did not show any substantial decrease. Leukemia mortality declined in most countries, whereas less favorable trends were registered for CNS neoplasms, particularly in Latin America. Around 2016, death rates from all neoplasms were 4 to 6 per 100,000 boys and 3 to 4 per 100,000 girls in Latin America, and 2 to 3 per 100,000 boys and approximately 2 per 100,000 girls in North America and Australasia., Conclusions: Childhood cancer mortality trends declined steadily in North America and Australasia, whereas they were less favorable in most Latin American countries. Priority must be given to closing the gap by providing high-quality care for all children with cancer worldwide., Lay Summary: Advances in childhood cancer management have substantially improved the burden of these neoplasms over the past 40 years, particularly in high-income countries. This study aimed to monitor recent trends in America and Australasia using mortality data from the World Health Organization. Trends in childhood cancer mortality continued to decline in high-income countries by approximately 2% to 3% per year in Japan, Korea, and Australia, and 1% to 2% in North America. Only a few Latin American countries showed favorable trends, including Argentina, Chile, and Mexico, whereas other countries with limited resources still lagged behind., (© 2021 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity., Methods: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis., Results: A total of 667,916 individuals were included with an overall median (P25-P75) age at recruitment of 62.3 (57-67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86-1.04; I 2  = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08-1.26; I 2  = 0%) and a similar HR in women (1.13; 95% CI: 0.82-1.56; I 2  = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77-0.85; I 2  = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89-1.03; I 2  = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity., Conclusions: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.

Background: The International Agency for Research on Cancer (IARC) recently classified opium use as a Group 1 carcinogen. However, much remains to be studied on the relation between opium and cancer. We designed the Iranian Opium and Cancer (IROPICAN) study to further investigate the association of opium use and cancers of the head and neck, bladder, lung, and colon and rectum. In this paper, we describe the rationale, design, and some initial results of the IROPICAN Study., Methods: The IROPICAN is a multi-center case-control study conducted in 10 provinces of Iran. The cases were all histologically confirmed and the controls were selected from hospital visitors who were free of cancer, were not family members or friends of the cancer patients, and were visiting the hospital for reasons other than their own ailment. The questionnaires included detailed questions on opium use (including age at initiation, duration, frequency, typical amount, and route), and potential confounders, such as tobacco use (e.g., cigarettes, nass and water-pipe), and dietary factors. Biological samples, including blood and saliva, were also collected., Results: The validation and pilot phases showed reasonably good validity, with sensitivities of 70% and 69% for the cases and controls, respectively, in reporting opium use. The results also showed excellent reliability, with intra-class correlation coefficients of 0.96 for ever opium use and 0.88 (95% CI: 0.80, 0.92) for regular opium use. In the main phase, we recruited 3299 cancer cases (99% response rate) and 3477 hospital visitor controls (89% response rate). The proportion of ever-use of opium was 40% among cases and 18% among controls., Conclusion: The IROPICAN study will serve as a major resource in studies addressing the effect of opium on risk of cancers of the head and neck, bladder, lung, and colon and rectum., (© 2021 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Descriptive epidemiology identifies associations between environmental exposures and health effects that require results from methodologically stronger studies before causation can be considered., Objective: To critically review the methodology and results of Sentieri, a descripitive study on residence in areas with one or more industrial source of pollution., Methods: We systematically reviewed the literature quoted by Sentieri for the selection of health effects of nine types of pollution sources of a-priori interest. We also reviewed and meta-analyzed the results of the first report of Sentieri, that analyzed mortality in 44 polluted sites (PS), and 17 causes of deaths during 1995-2002., Results: Among 159 study results quoted by Sentieri, 23.9 % were supportive of an association between residence near a pollution source and a health effect, 30.2 % were partially supportive, 10.7 % were not supportive, and 35.2 % were not relevant. Among 653 standardized mortality ratios for associations between PS-specific pollution sources and causes of death, 14.4% were significantly above 1.02, and 9.0% were significantly below 0.98. Among 48 meta-analysis, seven were significantly above 1.0, including five on exposure to asbestos., Conclusions: Sentieri exemplifies the limitations of descriptive environmental epidemiology studies, in which most hypotheses have limited prior support, most results do not show associations, data on potential confounders and other sources of bias are not available. Such studies tend to replicate well-known associations and occasionally can identify critical situations requiring more investigation, but cannot be used to infer causality either in general or in specific circumstances.

Three cohorts including the Fire Department of the City of New York (FDNY), the World Trade Center Health Registry (WTCHR), and the General Responder Cohort (GRC), each funded by the World Trade Center Health Program have reported associations between WTC-exposures and cancer. Results have generally been consistent with effect estimates for excess incidence for all cancers ranging from 6 to 14% above background rates. Pooling would increase sample size and de-duplicate cases between the cohorts. However, pooling required time consuming steps: obtaining Institutional Review Board (IRB) approvals and legal agreements from entities involved; establishing an honest broker for managing the data; de-duplicating the pooled cohort files; applying to State Cancer Registries (SCRs) for matched cancer cases; and finalizing analysis data files. Obtaining SCR data use agreements ranged from 6.5 to 114.5 weeks with six states requiring >20 weeks. Records from FDNY ( n = 16,221), WTCHR ( n = 29,372), and GRC ( n = 33,427) were combined de-duplicated resulting in 69,102 unique individuals. Overall, 7894 cancer tumors were matched to the pooled cohort, increasing the number cancers by as much as 58% compared to previous analyses. Pooling resulted in a coherent resource for future research for studies on rare cancers and mortality, with more representative of occupations and WTC- exposure.

Objectives: Predicted cancer mortality figures are useful for public health planning. We predicted cancer mortality rates in Israel, Hong Kong, Japan, the Philippines, Korea, Australia, Russia and Ukraine for the year 2020 using the most recent available data. We focused on breast cancer., Methods: We obtained cancer death certification and population data from the WHO and the United Nations Population Division databases. We derived figures for 10 major cancer sites and total cancers over 1970-2017. We predicted numbers of deaths and age-standardized mortality rates for 2020 through joinpoint regression models. We calculated the number of avoided deaths from 1994-2020., Results: Overall, total cancer mortality is predicted to decline. Russia had the highest all cancers rates in 2020, 151.9/100 000 men and 79.6 women; the Philippines had the lowest rate in men, 78.0/100 000, Korea in women, 47.5. Stomach cancer rates declined over the whole period in all countries considered, colorectal cancer since the late 1990s. Trends for pancreas were inconsistent. Predicted rates for lung and breast cancer were favourable; women from Hong Kong, Korea and Australia had lung cancer death rates higher than breast ones. Predicted rates for uterine, ovarian, prostate and bladder cancers and leukaemias were downward for most countries. Between 1994 and 2020, over 3.3 million cancer deaths were avoided in the considered countries, except for the Philippines where no reduction was observed., Conclusion: Predicted cancer rates were lower than in the European Union and the USA, even though falls started later and were less marked.

High mobility group A protein-2 (HMGA2) is an architectural transcription factor that binds to the A/T-rich DNA minor groove and is responsible for regulating transcriptional activity of multiple genes indirectly through chromatin change and assembling enhanceosome. HMGA2 is overexpressed in multiple tumor types, suggesting its involvement in cancer initiation and progression, thus, making it an ideal candidate for cancer diagnostic and prognostic. We performed a systematic review to examine the role of HMGA2 as a universal tumor cancer diagnostic and prognostic marker. We used Reporting Recommendations for Tumor Marker Prognostic Studies to systematically search OvidMedline, PubMed, and the Cochrane Library for English language studies, published between 1995 and June 2019. Meta-analysis provided pooled risk estimates and their 95% confidence intervals (CIs) for an association between overall survival and recurrence of cancers for studies with available estimates. We identified 42 eligible studies with a total of 5123 tumor samples in 15 types of cancer. The pooled percentage of HMGA2 gene expression in tumor samples was 65.14%. Meta-analysis showed that cancer patients with HMGA2 positive have significantly reduced survival, compared to patients without HMGA2 gene [pooled-hazard ratio (HR) = 1.85, 95% CI 1.48-2.22]. There was a positive association between cancer patients with HMGA2 overexpression and cancer recurrence though this association did not reach significance (pooled-HR = 1.44, 95% CI 0.80-2.07). Overexpression of HMGA2 was found in 15 types of cancer. There was an association between HMGA2 overexpression with reduced survival of cancer patients. HMGA2 is thus considered a promising universal tumor marker for prognostics.

Cancer mortality has declined over the last three decades in most high-income countries reflecting improvements in cancer prevention, diagnosis, and management. However, there are persisting and substantial differences in mortality, incidence, and survival worldwide. In order to provide an up-to-date overview of trends in mortality, incidence, and survival, we retrieved data from high-quality, population-based cancer registries for all cancers and 10 selected cancer sites in six high-income countries and the European Union. We computed age-standardized (world standard population) mortality and incidence rates, and applied joinpoint regression models. Mortality from all cancers and most common cancer sites has declined over the last 25 years, except for the pancreas and lung (in women). The patterns for incidence are less consistent between countries, except for a steady decrease in stomach cancer in both sexes and lung cancer in men. Survival for all cancers and the selected cancer sites increased in all countries, even if there is still a substantial variability. Although overall cancer death rates continue to decline, incidence rates have been levelling off among men and have been moderately increasing among women. These trends reflect changes in cancer risk factors, screening test use, diagnostic practices, and treatment advances. Many cancers can be prevented or treated effectively if they are diagnosed early. Population-based cancer incidence and mortality data can be used to focus efforts to decrease the cancer burden and regularly monitor progress towards cancer control goals.

We estimated mortality figures for 2019 in seven Latin American countries, with focus on breast cancer. We retrieved cancer death certification and population data from the WHO and PAHO databases. We obtained mortality statistics for Argentina, Brazil, Chile, Colombia, Cuba, Mexico and Venezuela for 1970-2015. We predicted current death numbers and age-standardised (world population) mortality rates using joinpoint regression models. Total cancer mortality is predicted to decline in all countries and both sexes, except Argentinian women. Cuba had the highest all cancer rates for 2019, 136.9/100,000 men and 90.4 women, while Mexico showed the lowest ones, 63.8/100,000 men and 61.9 women. Stomach cancer showed favourable trends over the whole period, while colorectal cancer only recently. Lung cancer rates declined in men, while in women they decreased slightly over the most recent years, only. In Cuban women, lung cancer rates overtook breast cancer ones. Breast cancer showed overall favourable trends, but rates are rising in young women. Prostate and uterine cancer had favourable trends. Pancreas, ovary, bladder and leukaemias showed slightly decreasing trends. Between 1990 and 2019, mortality from all neoplasms is predicted to fall by about 18% in Argentina, 26% in Chile, 14% in Colombia, 17% in Mexico and 13% in Venezuela, corresponding to almost 0.5 million avoided cancer deaths. No decline was observed in Brazil and Cuba. Of concern, the persisting high rates of (cervix) uterus cancer, the high lung cancer rates in Cuba, the possible increases in breast cancer in young women, and the lack of overall declines in Brazil, Cuba and Venezuelan men., (© 2019 UICC.)

Aim: To monitor trends in childhood cancer mortality in Europe., Methods: We calculated age-standardized mortality rates per 100,000 children (age 0-14 years) from 1990 to the last available calendar year, for all neoplasms and six main cancers in childhood, in selected European countries and geographic areas, plus the European Union (EU), using data from the World Health Organization database. We carried out a joinpoint regression analysis of mortality trends for all neoplasms, leukaemia and tumours of the nervous system. Results of the joinpoint regression were summarized through annual percent change (APC) for each identified linear segment, and weighted average APC (AAPC) over the whole period., Results: From 1990 to 2015, childhood total cancer mortality rates dropped by 2.8% per year in the EU, to reach 2.6/100,000 in the latest available calendar years. The greatest declines were in central-eastern countries (AAPCs -3% to -4%). Recent rates ranged between 1.7 and 4.3 deaths/100,000, with the highest values in central-eastern Europe. Leukaemia mortality rates in the EU decreased from 1.6 to 0.6/100,000 in the latest calendar years (AAPC -4%). The deepest declines were registered in central-eastern countries, though they still showed the highest rates (0.9). The lowest leukaemia mortality rates were in northern-western Europe (0.5/100,000), but also in the Czech Republic and Poland. Southern European countries showed comparatively high rates (0.8). Nervous system tumours showed relatively modest falls (AAPC: -1.7% in the EU)., Conclusions: Childhood cancer mortality continued to decline steady in Europe, though geographic differences persist. Further efforts are required to fill the gap, by promoting widespread and rational adoption of currently available treatment protocols., Competing Interests: Declaration of Competing Interest All authors have declared no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Evidence is emerging for a role of opiates in various cancers. In this study, we aimed to investigate the association between regular opium use and cancer incidence., Methods: This study was done in a population-based cohort of 50 045 individuals aged 40-75 years from northeast Iran. Data on participant demographics, diet, lifestyle, opium use, and different exposures were collected upon enrolment using validated questionnaires. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% CIs for the association between opium use and different cancer types., Findings: During a median 10 years of follow-up, 1833 participants were diagnosed with cancer. Use of opium was associated with an increased risk of developing all cancers combined (HR 1·40, 95% CI 1·24-1·58), gastrointestinal cancers (1·31, 1·11-1·55), and respiratory cancers (2·28, 1·58-3·30) in a dose-dependent manner (p trend <0·001). For site-specific cancers, use of opium was associated with an increased risk of developing oesophageal (1·38, 1·06-1·80), gastric (1·36, 1·03-1·79), lung (2·21, 1·44-3·39), bladder (2·86, 1·47-5·55), and laryngeal (2·53, 1·21-5·29) cancers in a dose-dependent manner (p trend <0·05). Only high-dose opium use was associated with pancreatic cancer (2·66, 1·23-5·74). Ingestion of opium (but not smoking opium) was associated with brain (2·15, 1·00-4·63) and liver (2·46, 1·23-4·95) cancers in a dose-dependent manner (p rend <0·01). We observed consistent associations among ever and never tobacco users, men and women, and individuals with lower and higher socioeconomic status., Interpretation: Opium users have a significantly higher risk of developing cancers in different organs of the respiratory, digestive, and urinary systems and the CNS. The results of this analysis show that regular use of opiates might increase the risk of a range of cancer types., Funding: World Cancer Research Fund International, Cancer Research UK, Tehran University of Medical Sciences, US National Cancer Institute, International Agency for Research on Cancer., (Copyright © 2020 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY-NC-ND 3.0 IGO license which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is properly cited. This article shall not be used or reproduced in association with the promotion of commercial products, services or any entity. There should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Vietnam is undergoing rapid socio-economic transition with an increasing cancer burden. The contribution of modifiable risk factors to cancers in Vietnam has not been studied. Therefore, we sought to evaluate the attributable causes of cancer in Vietnam., Methods: We reviewed the data on burden of cancer in Vietnam from 2 cancer registries in Hanoi and Ho Chi Minh City between 1995 and 2012. Next, we calculated the fractions of cancers occurring in 2018 attributable to established modifiable risk factors whose impact could be quantified. Data on exposure prevalence were obtained for the period from 2000 to 2010 from national sources wherever possible., Results: Cancer incidence in Vietnam has decreased slightly in both sexes. Cancer related to infectious agents decreased sharply, whereas cancer related to nutrition and metabolism has increased. In 2018, established carcinogens included in the analysis explained 47.0% of cancer burden in Vietnam. Chronic infections accounted for 29.1% of cancers (34.7% in men and 22.1% in women), tobacco smoking for 13.5% (23.9% in men and 0.8% in women), and alcohol drinking for 10.3%. Passive smoking was responsible for 8.8% of cancers in women. Other risk factors, including overweight or obesity, nulliparity, and low vegetable and fruit intake, accounted for < 1% of all cancers each., Conclusion: Cancer incidence is slowly decreasing in Vietnam, and the causes of more than half of cancers remain unexplained. This result underlines the need for further epidemiologic and fundamental research. Our findings confirm the notion that controlling oncogenic infections and decreasing tobacco smoking are the most effective approaches to reduce the burden of cancer in Vietnam, but other risk factors, including alcohol drinking and diet, should not be neglected.

Objective: To evaluate the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and overall and cause-specific mortality in the Golestan Cohort Study (GCS)., Methods: A total of 50 045 participants aged 40 years or older were recruited from Golestan Province, Iran, from 2004 to 2008 and followed for a mean of 10.64 years. The DASH diet score was calculated for each individual based on food groups. The primary outcome measure was death from any cause., Results: During 517 326 person-years of follow-up, 6763 deaths were reported. After adjustment for potential confounders, DASH diet score was inversely associated with risk of death from all causes and cancers [hazard ratio (HR): 0.86; 95% confidence interval (CI): 0.75, 0.98; and HR: 0.65; 95% CI: 0.47, 0.90, respectively]. A higher DASH diet score was associated with lower risk of gastrointestinal cancer mortality in men (HR: 0.55; 95% CI: 0.30, 0.99). A greater adherence to DASH diet was also associated with lower other-cancer mortality in women (HR: 0.50; 95% CI: 0.24, 0.99). No association between DASH diet score and cardiovascular disease mortality was observed, except that those dying of cardiovascular disease were younger than 50 years of age and smokers., Conclusions: Our findings suggest that maintaining a diet similar to the DASH diet is independently associated with reducing the risk of total death, cancers, and especially gastrointestinal cancers in men., (© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

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.)

Background: The number of older people living with cancer and cardiometabolic conditions is increasing, but little is known about how specific combinations of these conditions impact mortality., Methods: A total of 22,692 participants aged 65 years and older from four international cohorts were followed-up for mortality for an average of 10 years (8,596 deaths). Data were harmonized across cohorts and mutually exclusive groups of disease combinations were created for cancer, myocardial infarction (MI), stroke, and diabetes at baseline. Cox proportional hazards models for all-cause mortality were used to estimate the age- and sex-adjusted hazard ratio and rate advancement period (RAP) (in years)., Results: At baseline, 23.6% (n = 5,116) of participants reported having one condition and 4.2% (n = 955) had two or more conditions. Data from all studies combined showed that the RAP increased with each additional condition. Diabetes advanced the rate of dying by the most years (5.26 years; 95% confidence interval [CI], 4.53-6.00), but the effect of any single condition was smaller than the effect of disease combinations. Some combinations had a significantly greater impact on the period by which the rate of death was advanced than others with the same number of conditions, for example, 10.9 years (95% CI, 9.4-12.6) for MI and diabetes versus 6.4 years (95% CI, 4.3-8.5) for cancer and diabetes., Conclusions: Combinations of cancer and cardiometabolic conditions accelerate mortality rates in older adults differently. Although most studies investigating mortality associated with multimorbidity used disease counts, these provide little guidance for managing complex patients as they age., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The biologic effects of inorganic arsenic predominantly involve reaction of the trivalent forms with sulfhydryl groups in critical proteins in target cells, potentially leading to various toxicologic events including cancer. This mode of action is a threshold process, requiring sufficient concentrations of trivalent arsenic to disrupt normal cellular function. Nevertheless, cancer risk assessments for inorganic arsenic have traditionally utilized various dose-response models that extrapolate risks from high doses assuming low-dose linearity without a threshold. We present here an approach for a cancer risk assessment for inorganic arsenic in drinking water that involves considerations of this threshold process. Extensive investigations in mode of action analysis, in vitro studies (>0.1 µM), and in animal studies (>2 mg/L in drinking water or 2 mg/kg of diet), collectively indicate a threshold basis for inorganic arsenic-related cancers. These studies support a threshold for the effects of arsenic in humans of 50-100 µg/L in drinking water (about 65 µg/L). We then evaluate the epidemiology of cancers of the urinary bladder, lung, and skin and non-cancer skin changes for consistency with this calculated value, focusing on studies involving low-level exposures to inorganic arsenic primarily in drinking water (approximately <150 µg/L). Based on the relevant epidemiological studies with individual-level data, a threshold level for inorganic arsenic in the drinking water for these cancers is estimated to be around 100 µg/L, with strong evidence that it is between 50 and 150 µg/L, consistent with the value calculated based on mechanistic, in vitro and in vivo investigations. This evaluation provides an alternative mode of action-based approach for assessing health-protective levels for oral arsenic exposure based on the collective in vitro , in vivo , and human evidence rather than the use of a linear low-dose extrapolation based on default assumptions and theories.

Epidemiologic research on the role of fibers and other elongate mineral particles (EMP) and human diseases including cancers has generated a large body of literature over the last decades: nevertheless, there remain some questions for which the scientific community appears unable to reach consensus. Reasons for genuine differences in opinion include (i) ways in which exposures have been classified; (ii) methodological limitations of the available studies, (iii) criteria for the interpretation of study results, including potential underlying biological mechanisms, and (iv) methodology for integrating the evidence. Various approaches have been proposed in recent years to address these issues, which will be illustrated using examples from asbestos, talc, taconite, synthetic mineral fibers and silicon carbide, with emphasis on potential carcinogenic effects. Potential solutions include improved exposure and outcome assessment - including use of biomarkers and other molecular approaches, consideration of potential confounding and other sources of bias, implementation of guidelines for study quality assessment and evidence evaluation and integration., (Copyright © 2018. Published by Elsevier Inc.)

Background: High dietary intake or blood concentrations (as biomarkers of dietary intake) of vitamin C, carotenoids, and vitamin E have been associated with reduced risk of cardiovascular disease, cancer, and mortality, but these associations have not been systematically assessed., Objective: We conducted a systematic review and meta-analysis of prospective studies of dietary intake and blood concentrations of vitamin C, carotenoids, and vitamin E in relation to these outcomes., Design: We searched PubMed and Embase up to 14 February 2018. Summary RRs and 95% CIs were calculated with the use of random-effects models., Results: Sixty-nine prospective studies (99 publications) were included. The summary RR per 100-mg/d increment of dietary vitamin C intake was 0.88 (95% CI: 0.79, 0.98, I2 = 65%, n = 11) for coronary heart disease, 0.92 (95% CI: 0.87, 0.98, I2 = 68%, n = 12) for stroke, 0.89 (95% CI: 0.85, 0.94, I2 = 27%, n = 10) for cardiovascular disease, 0.93 (95% CI: 0.87, 0.99, I2 = 46%, n = 8) for total cancer, and 0.89 (95% CI: 0.85, 0.94, I2 = 80%, n = 14) for all-cause mortality. Corresponding RRs per 50-μmol/L increase in blood concentrations of vitamin C were 0.74 (95% CI: 0.65, 0.83, I2 = 0%, n = 4), 0.70 (95% CI: 0.61, 0.81, I2 = 0%, n = 4), 0.76 (95% CI: 0.65, 0.87, I2 = 56%, n = 6), 0.74 (95% CI: 0.66, 0.82, I2 = 0%, n = 5), and 0.72 (95% CI: 0.66, 0.79, I2 = 0%, n = 8). Dietary intake and/or blood concentrations of carotenoids (total, β-carotene, α-carotene, β-cryptoxanthin, lycopene) and α-tocopherol, but not dietary vitamin E, were similarly inversely associated with coronary heart disease, stroke, cardiovascular disease, cancer, and/or all-cause mortality., Conclusions: Higher dietary intake and/or blood concentrations of vitamin C, carotenoids, and α-tocopherol (as markers of fruit and vegetable intake) were associated with reduced risk of cardiovascular disease, total cancer, and all-cause mortality. These results support recommendations to increase fruit and vegetable intake, but not antioxidant supplement use, for chronic disease prevention.

Objectives: To examine the causes of premature mortality (<70 years) and associated risk factors in the Golestan Cohort Study., Design: Prospective., Setting: The Golestan Cohort Study in northeastern Iran., Participants: 50 045 people aged 40 or more participated in this population-based study from baseline (2004-2008) to August 2017, with over 99% success follow-up rate., Main Outcome Measures: The top causes of premature death, HR and their 95% CI and population attributable fraction (PAF) for risk factors., Results: After 444 168 person-years of follow-up (median of 10 years), 6347 deaths were reported, of which 4018 (63.3%) occurred prematurely. Ischaemic heart disease (IHD) accounted for 33.9% of premature death, followed by stroke (14.0%), road injuries (4.7%), stomach cancer (4.6%) and oesophageal cancer (4.6%). Significant risk/protective factors were: wealth score (HR for highest vs lowest quintile: 0.57, PAF for lowest four quintiles vs top quintile: 28%), physical activity (highest vs lowest tertile: 0.67, lowest two tertiles vs top tertile: 22%), hypertension (1.50, 19%), opium use (1.69, 14%), education (middle school or higher vs illiterate: 0.84, illiterate or primary vs middle school or higher: 13%), tobacco use (1.38, 11%), diabetes (2.39, 8%) and vegetable/fruit consumption (highest vs lowest tertile: 0.87, lowest two tertiles vs top tertile: 8%). Collectively, these factors accounted for 76% of PAF in men and 69% in women., Conclusion: IHD and stroke are the leading causes of premature mortality in the Golestan Cohort Study. Enhancing socioeconomic status and physical activity, reducing opium and tobacco use, increasing vegetable/fruit consumption and controlling hypertension and diabetes are recommended to reduce premature deaths., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

No systematic reviews are available on data from humans on cancer risk from exposure to permethrin, a widely used insecticide for which some animal studies have reported positive findings based on mechanisms that may not be relevant to humans. We identified potentially relevant articles through a search of electronic databases which included all studies of pesticide exposure and human cancer. A total of 18 articles were selected, including six identified from the list of references of other articles. Most articles were based on analyzes of the Agriculture Health Study (AHS); they provided no evidence of an increased risk of cancers of colon, rectum, pancreas, lung, melanoma, female breast, prostate, urinary bladder, as well as non-Hodgkin lymphoma (including its main subtypes), and leukemia. An increased risk of multiple myeloma was reported among AHS members with the highest tertile of estimated permethrin exposure (odds ratio 5.01; 95% confidence interval 2.41-10.42; p for trend <0.01). A subsequent analysis with a larger number of cases found a less pronounced association between permethrin exposure and risk of multiple myeloma; no exposed cases were reported in a separate study. Two case-control studies of childhood leukemia reported an association with biological markers of permethrin metabolites; in another study self-reported exposure to permethrin was associated with risk in children below 1 year of age, but not in older children. In conclusion, permethrin exposure does not seem to entail a risk of cancer in humans. Results on multiple myeloma and childhood leukemia are weak and inconsistent, and require replication in independent populations.

Elevated serum uric acid (SUA) is a marker of chronic inflammation and has been suggested to be associated with increased risk of cancer, but its antioxidant capacity would justify an anticancer effect. Previous meta-analyses did not include all available results. We conducted a systematic review of prospective studies on SUA level and risk of all cancers and specific cancers, a conducted a meta-analysis based on random-effects models for high versus low SUA level as well as for an increase in 1 mg/dl SUA. The relative risk of all cancers for high versus low SUA level was 1.11 (95% confidence interval: 0.94-1.27; 11 risk estimates); that for a mg/dl increase in SUA level was 1.03 (95% confidence interval: 0.99-1.07). Similar results were obtained for lung cancer (six risk estimates) and colon cancer (four risk estimates). Results for other cancers were sparse. Elevated SUA levels appear to be associated with a modest increase in overall cancer risk, although the combined risk estimate did not reach the formal level of statistical significance. Results for specific cancers were limited and mainly negative.

Objective: To evaluate whether cancer risks are increased among bitumen (asphalt) workers., Methods: Systematic review and meta-analysis of cancer risks (lung, upper aerodigestive tract (UADT), esophagus, bladder, kidney, stomach, and skin) and bitumen exposure. Certainty in the epidemiological evidence that bitumen-exposed workers experience increased cancer risks was rated using Grading of Recommendations Assessment, Development and Evaluation criteria., Results: After excluding lower-quality studies, lung cancer risks were not increased among bitumen-exposed workers (meta-relative risk [RR] 0.94, 95% CI 0.74 to 1.20, eight studies). Increased risks of UADT and stomach cancers were observed (meta-RR 1.31, 95% CI 1.03 to 1.67, 10 studies and meta-RR 1.29, 95% CI 1.03 to 1.62, seven studies, respectively)., Conclusions: Except for lung cancer, evidence for increased cancer risks among bitumen-exposed workers was judged to be of low certainty, due to inadequate exposure characterization and unmeasured confounders (coal tar exposure, smoking, and alcohol consumption).

Background: Previous studies have found associations between oral health and mortality, but the majority of previous studies have been conducted in high-income countries., Methods: We used data from the Golestan Cohort Study, a study of 50 045 people aged 40 to 75 years in north eastern Iran, recruited from January 2004 to June 2008. Tooth loss and decayed, missing and filled teeth (DMFT) were assessed by trained physicians. Frequency of tooth brushing and use of dentures were self-reported. Cause-specific mortality was ascertained through March 2014. We calculated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations between the oral health variables, overall mortality and cause-specific mortality., Results: Participants with the greatest tooth loss had increased overall mortality (HR 1.43; 95% CI: 1.28, 1.61) compared with those with the least tooth loss; similar estimates were observed for DMFT score. For cause-specific mortality, an increased risk of death was found for tooth loss and mortality from cardiovascular disease (HR 1.33; 95% CI: 1.13, 1.56), cancer (HR 1.30; 95% CI: 1.03, 1.65) and injuries (HR 1.99; 95% CI: 1.28, 3.09). The associations between oral health and injury mortality were strongly attenuated after exclusion of participants with comorbid conditions at baseline. No statistical interaction was found between denture use and tooth loss or DMFT on mortality., Conclusions: Poor oral health appears to predict overall and cause-specific mortality in populations in economic transition. Investigation of the underlying mechanisms might provide an important contribution to reducing mortality., (Published by Oxford University Press on behalf of the International Epidemiological Association 2017. This work is written by US Government employees and is in the public domain in the United States.)

Introduction: Use of non-cigarette tobacco products such as cigars and pipe has been increasing, even though these products entail exposure to similar carcinogens to those in cigarettes. More research is needed to explore the risk of these products to guide cancer prevention efforts. Methods: To measure the association between cigars and/or pipe smoking, and cancer incidence in men, we performed meta-analyses of data from five prospective cohorts. Cox regression was used to evaluate the association between different aspects of cigars and pipe smoking and risk of each smoking-related cancer (head and neck, esophagus, lung, stomach, liver, pancreas, kidney, and bladder) for each study. Adjusted HRs were combined using random-effects models. Results: Cigars and/or pipe smokers were at increased risk for head and neck [HR, 1.51; 95% confidence interval (CI), 1.22-1.87], lung (HR, 2.04; 95% CI, 1.68-2.47), and liver cancers (HR, 1.56; 95% CI, 1.08-2.26). Ever-smokers of cigars and/or pipe had an increased risk of developing a smoking-related cancer when compared with never smokers of any tobacco product (overall HR, 1.07; 95% CI, 1.03-1.12). The risk for smoking-related cancers was also increased in mixed smokers who smoked cigars or pipe as well as cigarettes, even when they were smoking predominantly pipe or cigars. Discussion: This pooled analysis highlights the increased risk for smoking-related cancers, particularly for lung and head and neck cancers in exclusive and predominant smokers (former and current) of cigars and pipe. Tobacco prevention efforts should include these products in addition to cigarettes. Cancer Prev Res; 10(12); 704-9. ©2017 AACR ., (©2017 American Association for Cancer Research.)

The East Harlem (EH), Central Harlem (CH), and Upper East Side (UES) neighborhoods of New York City are geographically contiguous to tertiary medical care, but are characterized by cancer mortality rate disparities. This ecological study aims to disentangle the effects of race and neighborhood on cancer deaths. Mortality-to-incidence ratios were determined using neighborhood-specific data from the New York State Cancer Registry and Vital Records Office (2007-2011). Ecological data on modifiable cancer risk factors from the New York City Community Health Survey (2002-2006) were stratified by sex, age group, race/ethnicity, and neighborhood and modeled against stratified mortality rates to disentangle race/ethnicity and neighborhood using logistic regression. Significant gaps in mortality rates were observed between the UES and both CH and EH across all cancers, favoring UES. Mortality-to-incidence ratios of both CH and EH were similarly elevated in the range of 0.41-0.44 compared with UES (0.26-0.30). After covariate and multivariable adjustment, black race (odds ratio=1.68; 95% confidence interval: 1.46-1.93) and EH residence (odds ratio=1.20; 95% confidence interval: 1.07-1.35) remained significant risk factors in all cancers' combined mortality. Mortality disparities remain among EH, CH, and UES neighborhoods. Both neighborhood and race are significantly associated with cancer mortality, independent of each other. Multivariable adjusted models that include Community Health Survey risk factors show that this mortality gap may be avoidable through community-based public health interventions.

Objectives: To evaluate, among the elderly, the association of self-rated health (SRH) with mortality, and to identify determinants of self-rating health as "at-least-good"., Study Design: Individual data on SRH and important covariates were obtained for 424,791 European and United States residents, ≥60 years at recruitment (1982-2008), in eight prospective studies in the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES). In each study, adjusted mortality ratios (hazard ratios, HRs) in relation to SRH were calculated and subsequently combined with random-effect meta-analyses., Main Outcome Measures: All-cause, cardiovascular and cancer mortality., Results: Within the median 12.5 years of follow-up, 93,014 (22%) deaths occurred. SRH "fair" or "poor" vs. "at-least-good" was associated with increased mortality: HRs 1.46 (95% CI 1·23-1.74) and 2.31 (1.79-2.99), respectively. These associations were evident: for cardiovascular and, to a lesser extent, cancer mortality, and within-study, within-subgroup analyses. Accounting for lifestyle, sociodemographic, somatometric factors and, subsequently, for medical history explained only a modest amount of the unadjusted associations. Factors favourably associated with SRH were: sex (males), age (younger-old), education (high), marital status (married/cohabiting), physical activity (active), body mass index (non-obese), alcohol consumption (low to moderate) and previous morbidity (absence)., Conclusion: SRH provides a quick and simple tool for assessing health and identifying groups of elders at risk of early mortality that may be useful also in clinical settings. Modifying determinants of favourably rating health, e.g. by increasing physical activity and/or by eliminating obesity, may be important for older adults to "feel healthy" and "be healthy"., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Large studies are needed to evaluate socioeconomic inequality for site-specific cancer mortality. We conducted a longitudinal census-based national study to quantify the relative inequality in cancer mortality among educational levels in Italy., Methods: We linked the 2011 Italian census with the 2012 and 2013 death registries. Educational inequality in overall cancer and site-specific cancer mortality were evaluated by computing the mortality rate ratio (MRR)., Results: A total of 35,708,445 subjects aged 30-74 years and 147,981 cancer deaths were registered. Compared to the lowest level of education (none or primary school), the MRR for all cancers in the highest level (university) was 0.57 (95% CI 0.55; 0.58) in men and 0.84 (95% CI 0.81; 0.87) in women. Higher education was associated with reduced risk of mortality from lip, oral cavity, pharynx, oesophagus, stomach, colon and liver in both sexes. Higher education (university) was associated with decreased risk of lung cancer in men (MRR: 0.43, 95% CI 0.41; 0.46), but not in women (MRR: 1.00, 95% CI 0.92; 1.10). Highly educated women had a reduced risk of mortality from cervical cancer than lower educated women (MRR: 0.39, 95% CI 0.27; 0.56), but they had a similar risk for breast cancer (MRR: 1.01, 95% CI 0.94; 1.09)., Conclusions: Education is inversely associated with total cancer mortality, and the association was stronger in men. Different patterns and trends in tobacco smoking in men and women account for at least most of the gender differences.

Objective: The aim of this study was to update the analysis of mortality of a cohort of talc miners and millers in Northern Italy., Methods: We analyzed the mortality during 1946 to 2013 of 1722 male workers in an asbestos-free talc mine (1166 miners and 556 millers) employed during 1946 to 1995., Results: The overall standardized mortality ratio (SMR) was 1.24 [95% confidence interval (95% CI) 1.17 to 1.32]; no deaths were observed from pleural cancer; mortality from lung cancer was not increased. Mortality from pneumoconiosis was increased (SMR 26.62; 95% CI 20.71 to 33.69), in particular among miners, and was associated with duration of employment and time since first employment., Conclusions: We confirmed the lack of association between exposure to asbestos-free talc, lung cancer, and mesothelioma. Increased mortality from pneumoconiosis among miners is attributable to past exposure to silica.

We studied the associations of leukocyte telomere length (LTL) with all-cause, cardiovascular disease, and cancer mortality in 12,199 adults participating in 2 population-based prospective cohort studies from Europe (ESTHER) and the United States (Nurses' Health Study). Blood samples were collected in 1989-1990 (Nurses' Health Study) and 2000-2002 (ESTHER). LTL was measured by quantitative polymerase chain reaction. We calculated z scores for LTL to standardize LTL measurements across the cohorts. Cox proportional hazards regression models were used to calculate relative mortality according to continuous levels and quintiles of LTL z scores. The hazard ratios obtained from each cohort were subsequently pooled by meta-analysis. Overall, 2,882 deaths were recorded during follow-up (Nurses' Health Study, 1989-2010; ESTHER, 2000-2015). LTL was inversely associated with age in both cohorts. After adjustment for age, a significant inverse trend of LTL with all-cause mortality was observed in both cohorts. In random-effects meta-analysis, age-adjusted hazard ratios for the shortest LTL quintile compared with the longest were 1.23 (95% confidence interval (CI): 1.04, 1.46) for all-cause mortality, 1.29 (95% CI: 0.83, 2.00) for cardiovascular mortality, and 1.10 (95% CI: 0.88, 1.37) for cancer mortality. In this study population with an age range of 43-75 years, we corroborated previous evidence suggesting that LTL predicts all-cause mortality beyond its association with age., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

Background: Questions remain about the strength and shape of the dose-response relationship between fruit and vegetable intake and risk of cardiovascular disease, cancer and mortality, and the effects of specific types of fruit and vegetables. We conducted a systematic review and meta-analysis to clarify these associations., Methods: PubMed and Embase were searched up to 29 September 2016. Prospective studies of fruit and vegetable intake and cardiovascular disease, total cancer and all-cause mortality were included. Summary relative risks (RRs) were calculated using a random effects model, and the mortality burden globally was estimated; 95 studies (142 publications) were included., Results: For fruits and vegetables combined, the summary RR per 200 g/day was 0.92 [95% confidence interval (CI): 0.90-0.94, I 2  = 0%, n  = 15] for coronary heart disease, 0.84 (95% CI: 0.76-0.92, I 2  = 73%, n  = 10) for stroke, 0.92 (95% CI: 0.90-0.95, I 2  = 31%, n  = 13) for cardiovascular disease, 0.97 (95% CI: 0.95-0.99, I 2  = 49%, n  = 12) for total cancer and 0.90 (95% CI: 0.87-0.93, I 2  = 83%, n  = 15) for all-cause mortality. Similar associations were observed for fruits and vegetables separately. Reductions in risk were observed up to 800 g/day for all outcomes except cancer (600 g/day). Inverse associations were observed between the intake of apples and pears, citrus fruits, green leafy vegetables, cruciferous vegetables, and salads and cardiovascular disease and all-cause mortality, and between the intake of green-yellow vegetables and cruciferous vegetables and total cancer risk. An estimated 5.6 and 7.8 million premature deaths worldwide in 2013 may be attributable to a fruit and vegetable intake below 500 and 800 g/day, respectively, if the observed associations are causal., Conclusions: Fruit and vegetable intakes were associated with reduced risk of cardiovascular disease, cancer and all-cause mortality. These results support public health recommendations to increase fruit and vegetable intake for the prevention of cardiovascular disease, cancer, and premature mortality., (© The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association)