Introduction Socioeconomic inequalities are key contributors to cancer disparities. We explored the associations between individual-level socioeconomic status (SES) indicators (composite wealth score, educational attainment and rural/urban residence) and site-specific cancer incidence and mortality.Methods For this prospective study, we used data from 49 776 participants of the Golestan Cohort Study in northeastern Iran, enrolled in 2004–2008. Follow-up continued until first primary cancer diagnosis, death, loss to follow-up, or 31 March 2021. We used Cox proportional hazard regression models to estimate HRs and 95% CI, adjusted for several cancer risk factors and all SES indicators.Results Over a 14-year median follow-up, the highest wealth score quartile, compared with the lowest, was associated with reduced oesophageal (HR=0.61; 95% CI 0.43 to 0.88) and gastric (HR=0.61; 95% CI 0.43 to 0.86) but elevated breast (HR=2.54; 95% CI 1.32 to 4.89) cancer incidence. The highest education level, compared with none, was associated with reduced oesophageal (HR=0.43; 95% CI 0.24 to 0.79), gastric (HR=0.54; 95% CI 0.35 to 0.84), hepatobiliary (HR=0.33; 95% CI 0.13 to 0.83) and lung (HR=0.44; 95% CI 0.20 to 1.00) cancer incidence. Urban residence was associated with decreased oesophageal (HR=0.63; 95% CI 0.44 to 0.90) but increased colorectal (HR=1.72; 95% CI 1.17 to 2.54), breast (HR=2.37; 95% CI 1.52 to 3.71), hepatobiliary (HR=1.70; 95% CI 1.00 to 2.87) and prostate (HR=2.60; 95% CI 1.24 to 5.45) cancer incidence. Cancer mortality analyses showed similar associations though a few results were not statistically significant due to small sample sizes.Conclusions Low wealth score, lack of formal education and rural residence were associated with disparate cancer incidence and mortality, particularly gastrointestinal cancers, in this predominantly rural population from a low- and middle-income country.

BACKGROUND:Opium consumption, a recognized carcinogen, is associated with lung cancer. However, the relative contributions of its potentially carcinogenic constituents to lung cancer risk remain unclear. METHODS:We conducted a nested case-control study among the opium users in the Golestan Cohort Study, including 53 incident lung cancer cases and 53 controls matched on age, sex, tobacco use, place of residence, and enrollment time. Urinary biomarkers of opioids, volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and creatinine were measured in baseline samples. Adjusted logistic regression analyses, as well as mediation analyses, were used to evaluate the associations between biomarker concentrations and lung cancer incidence. RESULTS:We found statistically significant associations between 3- and 6- glucuronides of morphine, as well as metabolites of acrylonitrile/ethylene oxide (2-hydroxyethyl mercapturic acid) and propylene oxide (2-hydroxypropyl mercapturic acid), and lung cancer among opium users, especially those who smoked opium. Associations between VOC metabolites and lung cancer were independent of opioid biomarkers, and mediation analysis showed no evidence that VOCs mediate the effects of opioid biomarkers on lung cancer. No associations were observed for PAH biomarkers, cotinine and NNAL. CONCLUSIONS:Our findings provide biochemical evidence supporting the association between opium use and lung cancer, highlighting independent mechanisms related to both opioid and non-opioid components of opium, with varying effects by route of use. IMPACT:Opioids and chemical constituents produced during opium consumption must be considered in cancer risk assessment.

BACKGROUND:A large proportion of the global population uses solid fuels for household purposes, and limited evidence from previous studies suggests that it might be associated with reduced renal function. OBJECTIVES:To investigate the association between household use of different types of fuels and kidney disease-related mortality. METHODS:We analyzed data from the Golestan Cohort Study, a population-based prospective cohort study conducted in northeastern Iran, with 50 045 individuals aged 40-75 years enrolled in the period 2004-2008 and followed through April 2023. Information about household fuel use was collected using validated questionnaires. We estimated adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using Cox proportional hazards models. The outcome of interest was death due to any kidney disease, excluding kidney cancer (ICD-10 codes: N00-N19 and N25-N29). RESULTS:During 724,063.62 person-years of follow-up, 262 participants died due to kidney disease. The risk of kidney disease-related mortality was higher with increasing duration of biomass use for cooking or house heating (HR for every 10-year increase: 1.20; 95% CI: 1.04-1.37), while it was not associated with increased duration of using kerosene (10-y HR: 1.09; 95% CI: 0.95-1.24) or gas (10-y HR: 1.00; 95% CI: 0.86-1.16). Estimates for lifetime duration of fuel burning for both cooking and house heating (exclusive fuel use) did not differ according to whether used heating stoves were chimney-equipped or not for kerosene, while they differed for biomass (10-y HR, chimney-equipped: 1.06 [95% CI: 0.95-1.18]; 10-y HR, not chimney-equipped: 1.19 [95% CI: 1.06-1.34]; P difference = 0.025). DISCUSSION:The findings of our study suggest that burning biomass for household purposes under poor ventilating conditions is associated with kidney disease-related mortality.

BACKGROUND:Healthy eating patterns are associated with reduced overall and select cause-specific mortality. Whether dietary quality and mortality risk differ by census-level neighborhood socioeconomic deprivation has not been well studied. OBJECTIVES:This study aimed to investigate whether dietary quality, measured by the Healthy Eating Index (HEI)-2020, is associated with all-cause and 12 cause-specific mortality, and if the association is modified by a Neighborhood Socioeconomic Deprivation Index (NSDI). METHODS:Prospective analysis of 544,837 American participants (321,756 males and 223,081 females), aged 50-71 y from the National Institutes of Health (NIH)-AARP Diet and Health Study from baseline (1995/1996 through 31 December, 2019). HEI-2020 was calculated using dietary data from self-reported responses to a 124-item baseline food frequency questionnaire. NSDI was estimated based on census variables and developed using principal component analysis. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS:During follow-up to 24.2 y, 282,073 deaths occurred. HEI-2020 quintile (Q5), compared with the Q1 was associated with reduced all-cause mortality (HR: 0.86; 95% CI: 0.85, 0.87) and death from 11 causes (HRs: 0.61-0.90), including cancer, cardiovascular, respiratory, stroke, infections, diabetes, kidney, liver, and autoimmune diseases, external, and other causes, but not neurological disease. Stronger reductions were observed among those in less deprived neighborhoods (NSDI Q1) than more deprived (Q5) for respiratory [HEI-2020 HR (95% CI) 0.67 (0.60, 0.76) compared with 0.78 (0.71, 0.85), P-interaction = 0.0001] and neurological disease mortality [0.90 (0.81, 0.99) compared with 1.06 (0.98, 1.16), P-interaction = 0.002], after correction for multiple comparisons (Bonferroni threshold P < 0.004). CONCLUSIONS:Dietary quality was protective for all-cause and most cause-specific mortality in middle-aged and older people, but less protective for respiratory and neurological disease among those living in more deprived neighborhoods.

The prevalence of waterpipe smoking (WPS) is increasingly recognised as a growing global public health concern. Available studies show that WPS exposes users to toxicants at levels similar to or higher than those in cigarette smoke, contributing to respiratory disease, cardiovascular damage and cancer. The WHO has flagged WPS as a growing threat, especially among adolescents and young adults, where use is rapidly increasing. Yet research progress is constrained by small samples, inconsistent exposure measures and inadequate adjustment for confounders. These limitations highlight the need for more rigorous epidemiological, clinical and toxicological studies. Importantly, the persistence and expansion of WPS cannot be explained solely by individual behaviours or perceptions of health risk. A range of socioeconomic, political and commercial forces-including industry marketing, weak regulatory oversight, cultural acceptance, low cost and the spread of waterpipe cafés-continues to drive WPS and shape patterns of use. These structural factors are likely to undermine the impact of current public health measures but remain under-researched. Expanding the evidence based on these upstream determinants is crucial for developing more effective and context-appropriate policies. In response to these challenges, experts from multiple disciplines convened in June 2024 to examine the evolving WPS epidemic. Participants emphasised the need for comprehensive, multisectoral strategies that integrate robust research, strengthen surveillance systems and target public awareness initiatives. The meeting concluded with a set of recommendations outlining priority research areas and a strategic roadmap aimed at addressing the complex and escalating public health threat posed by WPS.

BACKGROUND:The constituents of tobacco smoke that specifically contribute to lung cancer risk have yet to be fully identified. We evaluated associations between biomarkers of potentially harmful constituents-polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, nicotine, and volatile organic compounds-and lung cancer incidence among US women. METHODS:In a case-cohort study nested within the Sister Study (women aged 35-74 years at baseline, enrolled 2003-2009), data were obtained for a random subcohort and all remaining incident lung cancers through September 2017 (median follow-up = 9.6 years), stratified by race and ethnicity (Hispanic, non-Hispanic Black, non-Hispanic White, others) and smoking status (current, former, never). The analytic sample included 356 cases and 433 noncases. We quantified 30 biomarkers in baseline urine samples and calculated hazard ratios (HRs) for associations between 1-unit increase in biomarker concentrations (log-scale) and lung cancer incidence using weighted Cox regression models adjusted for urinary creatinine and demographic, health, and lifestyle factors. RESULTS:Among women who were currently smoking at enrollment, positive associations were observed for biomarkers of polycyclic aromatic hydrocarbons (naphthalene, phenanthrene, pyrene, fluorene; HRs = 1.4-5.3), tobacco-specific nitrosamines (particularly 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone [nicotine-derived nitrosamine ketone]; HRs = 1.3-2.2), and volatile organic compounds (xylene, acrylamide, acrylonitrile, 1,2-dibromoethane and/or vinyl-chloride and/or ethylene-oxide and/or acrylonitrile, acrolein, styrene and/or ethylbenzene, benzene, dimethylformamide and/or methylisocyanate, 1,3-butadiene, crotonaldehyde, isoprene; HRs = 1.6-4.4). Associations with biomarkers of most polycyclic aromatic hydrocarbons, nicotine-derived nitrosamine ketone, xylene, and dimethylformamide and/or methylisocyanate remained after additional adjustment for smoking frequency, duration, and nicotine metabolites. In women who did not smoke, positive associations were observed for styrene and/or ethylbenzene and dimethylformamide and/or methylisocyanate biomarkers. CONCLUSION:Exposure to polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, and several volatile organic compounds through tobacco smoking were associated with increased lung cancer risk among women.

Although the prevalence of waterpipe smoking is increasing worldwide, evidence on its health hazards, including cancer, is limited. We examined the association between waterpipe smoking and head and neck squamous cell carcinoma (HNSCC) and its subsites. We analyzed data of 918 cases and 3477 controls from the IROPICAN study. Multiple logistic regression models estimated the odds ratios (OR) and 95% confidence intervals (CI). We additionally excluded cigarette smokers, opium users, and nass users to study the association between exclusive waterpipe smoking and HNSCC. The crude OR for ever waterpipe smoking was 1.0 (95% CI: 0.8, 1.3), which decreased to 0.8 (95% CI: 0.6, 1.1) after adjusting for confounding variables. However, we observed statistically non-significant elevated odds of HNSCC (OR: 1.3, 95% CI: 0.9, 1.9), while a significant excess odds of laryngeal cancer (OR: 2.5, 95% CI: 1.0, 5.7) in exclusive waterpipe smokers compared to never tobacco users. Additionally, an especially high OR was observed for laryngeal cancer in exclusive waterpipe smokers with more than 20 years of use (OR: 4.9, 95% CI: 1.7, 14.7). Initiating exclusive waterpipe smoking before the age of 20 was also significantly associated with increased odds of HNSCC (OR: 2.9, 95% CI: 1.3, 6.7) and laryngeal cancer (OR: 9.0, 95% CI: 2.1, 38.2). In conclusion, although no association was found between waterpipe smoking and HNSCC, exclusive waterpipe smoking, particularly at high doses and long duration, seems to lead to an increased risk of HNSCC, especially laryngeal cancer. Larger studies with sufficient power are warranted.

Evidence is inconclusive regarding the associations of body size and occupational physical activity (PA) during the life course with gastrointestinal cancers. We analyzed data from the Golestan Cohort Study, a population-based, prospective cohort study from Iran, with 50 045 individuals aged 40-75 years enrolled during 2004-2008 and followed through April 2023. Body size during adolescence, early adulthood, and at cohort baseline was assessed using validated pictograms. Large adolescent body size was associated with total gastrointestinal cancers (hazard ratio [HR] = 1.09; 95% CI, 1.02-1.16) and liver cancer (HR = 1.49; 95% CI, 1.11-2.01). Large early-adulthood body size was associated with liver cancer (HR = 1.85; 95% CI, 1.35-2.52). Compared with normal weight during all stages, overweight or obesity during adolescence only or early adulthood only were associated with stomach cancer, esophageal squamous cell carcinoma, and liver cancer. Lower levels of adolescent occupational PA were associated with colon cancer (HR = 1.39; 95% CI, 1.10-1.75), whereas lower levels at cohort baseline were positively associated with colon cancer and inversely associated with rectal cancer. Our findings suggest that timing of obesity during the life course might differently affect risk of gastrointestinal cancers, whereas occupational PA was associated with colon cancer only.

Chronic respiratory diseases (CRDs) are the third leading cause of death worldwide. Data of the associations between specific volatile organic compounds (VOCs), a major component of air pollution and tobacco smoke, and subsequent CRD mortality in the general population are scarce. In a case-cohort analysis within the population-based Golestan cohort study (n = 50045, aged 40–75 years, 58

Abstract Background The global burden of non-alcoholic fatty liver disease (NAFLD) has significantly risen over the past decade. Dietary intake strongly influences its development and should be a component of any prevention and treatment plan strategy. Dietary pattern analysis enables the investigation of the overall diet and permits the consideration of interactions and cumulative effects of dietary components. The current study aimed to systematically review observational studies and intervention trials to determine the associations between various dietary patterns and NAFLD. Methods The protocol was written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Embase, and the Cochrane Library. We included studies that reported a priori dietary pattern (i.e., diet quality scores) or a posteriori method, which identified existing eating patterns (i.e., principal component analysis) in adult participants. Two investigators conducted independent screening, extraction, and quality assessment using the Newcastle‒Ottawa or Jadad scale. A third reviewer resolved conflicts. Results We identified 27 relevant observational and 16 interventional studies from 16 countries. A Mediterranean or DASH diet might prevent and improve NAFLD, whereas dietary patterns such as Western dietary patterns characterized by high consumption of sweets and animal foods such as red meat and fast food are positively associated with NAFLD. A low-carbohydrate diet effectively prevents and treats NAFLD; however, we need more research on the effects of a low-fat diet and the type of fats. Conclusion Healthy dietary patterns, mainly plant-based or adjusted macronutrient distributions, such as the adoption of a low-carbohydrate diet, are linked to a reduced risk of NAFLD and could halt its progression. We proposed recommendations for future studies to fill the gap in knowledge regarding the management of NAFLD via dietary modifications.

Background: We aimed to examine the effects of age, diagnosis year (calendar period) and birth year (cohort) on the incidence trends of breast cancer among Golestan women, Northeast Iran, 2004-2018. Methods: Incidence data were obtained by residential status (urban/rural) and ethnic region (Turkmens/nonTurkmens). We calculated age -standardized incidence rates (ASRs) per 100,000 person -years. The estimated annual percentage change (EAPC) were calculated, and age -period -cohort (APC) models fitted to assess nonlinear effects of period and cohort as incidence rate ratios (IRRs). Results: The total number of female breast cancer cases in Golestan, 2004-2018, were 3853, with an overall ASR of 31.3. We found higher rates in urban population (40.5) and non-Turkmens region (38.5) compared to rural area (20.8) and Turkmens region (20.2), respectively. There were increasing trends in incidence rates overall (EAPC= 4.4; 95%CI: 2.2, 6.7), with greater changes in rural areas (EAPC=5.1), particularly among nonTurkmens (EAPC=5.8). The results of the APC analysis indicate the presence of significant non-linear cohort effects with increasing IRRs across successive birth cohorts (IRR=0.1 and IRR= 2.6 for the oldest and the youngest birth cohorts vs. the reference birth cohort, respectively). Conclusion: We found increasing trends in breast cancer incidence among Golestan women over the study period, with disparities in patterns and trends by residence area and ethnic region. The observed cohort effects suggest an increasing prevalence of key risk factors for breast cancer in this Iranian population. Further investigations are warranted to clarify the relationships between determinants such as reproductive factors and ethnicity in the region.

Introduction: Although lung cancer prediction models are widely used to support risk -based screening, their performance outside Western populations remains uncertain. This study aims to evaluate the performance of 11 existing risk prediction models in multiple Asian populations and to refit prediction models for Asians. Methods: In a pooled analysis of 186,458 Asian eversmokers from 19 prospective cohorts, we assessed calibration (expected -to -observed ratio) and discrimination (area under the receiver operating characteristic curve [AUC]) for each model. In addition, we developed the "Shanghai models" to better refine risk models for Asians on the basis of two well -characterized population -based prospective cohorts and externally validated them in other Asian cohorts. Results: Among the 11 models, the Lung Cancer Death Risk Assessment Tool yielded the highest AUC (AUC [95% confidence interval (CI)] = 0.71 [0.67-0.74] for lung cancer death and 0.69 [0.67-0.72] for lung cancer incidence) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model had good calibration overall (expected -to -observed ratio [95% CI] = 1.06 [0.90-1.25]). Nevertheless, these models substantially underestimated lung cancer risk among Asians who reported less than 10 smoking pack -years or stopped smoking more than or equal to 20 years ago. The Shanghai models were found to have marginal improvement overall in discrimination (AUC [95% CI] = 0.72 [0.69-0.74] for lung cancer death and 0.70 [0.67- 0.72] for lung cancer incidence) but consistently outperformed the selected Western models among lowintensity smokers and long-term quitters. Conclusions: The Shanghai models had comparable performance overall to the best existing models, but they improved much in predicting the lung cancer risk of lowintensity smokers and long-term quitters in Asia. (c) 2023 Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer.

BACKGROUND:Exposure to ambient air pollution is associated with a significant number of deaths. Much of the evidence associating air pollution with adverse effects is from North American and Europe, partially due to incomplete data in other regions limiting location specific examinations. The aim of the current paper is to leverage satellite derived air quality data to examine the relationship between ambient particulate matter and all-cause and cause-specific mortality in Asia. METHODS:Six cohorts from the Asia Cohort Consortium provided residential information for participants, recruited between 1991 and 2008, across six countries (Bangladesh, India, Iran, Japan, South Korea, and Taiwan). Ambient particulate material (PM2·5) levels for the year of enrolment (or 1998 if enrolled earlier) were assigned utilizing satellite and sensor-based maps. Cox proportional models were used to examine the association between ambient air pollution and all-cause and cause-specific mortality (all cancer, lung cancer, cardiovascular and lung disease). Models were additionally adjusted for urbanicity (representing urban and built characteristics) and stratified by smoking status in secondary analyses. Country-specific findings were pooled via random-effects meta-analysis. FINDINGS:More than 300,000 participants across six cohorts were included, representing more than 4-million-person years. A positive relationship was observed between a 5 µg/m (Dockery et al., 1993) increase in PM2·5 and cardiovascular mortality (HR: 1·06, 95 % CI: 0.99, 1·13). The additional adjustment for urbanicity resulted in increased associations between PM2.5 and mortality outcomes, including all-cause mortality (1·04, 95 % CI: 0·97, 1·11). Results were generally similar regardless of whether one was a current, never, or ex-smoker. INTERPRETATION:Using satellite and remote sensing technology we showed that associations between PM2.5 and all-cause and cause-specific Hazard Ratios estimated are similar to those reported for U.S. and European cohorts. FUNDING:This project was supported by the Health Effects Institute. Grant number #4963-RFA/18-5. Specific funding support for individual cohorts is described in the Acknowledgements.

ObjectivesTo determine the associations between waterpipe use, duration, and intensity of use with prevalence and incidence of metabolic syndrome and its components (increased waist circumference, triglycerides, fasting glucose, blood pressure and decreased high-density lipoprotein cholesterol).MethodsWe conducted cross-sectional and prospective analyses using data from the Pars Cohort Study in southern Iran, encompassing 9,264 participants at the baseline, and 5,002 randomly selected in a repeated follow-up. We used multivariate logistic regression models adjusted for age, sex, education, wealth score, physical activity and cigarette pack-years to report odds ratios (OR) and 95% confidence intervals (CI).ResultsAmong 9,264 participants, 3,119 (33.7%) had metabolic syndrome, and 3,482 (37.6%) had ever smoked waterpipe, with both more common in women than in men. In adjusted models, former waterpipe use was significantly associated with prevalence (OR = 1.43, 95% CI: 1.23–1.68) and incidence (OR = 1.57, 95% CI: 1.19–2.06) of the metabolic syndrome while current waterpipe use was not. Past use was associated with increased risk in all components of metabolic syndrome; current use was associated with increases in all except high blood glucose and hypertension. Past waterpipe users had higher waterpipe use intensity (before quitting) in comparison with current users (2.3 vs. 2.0 waterpipes per day, p < 0.01) and had started waterpipe smoking at a younger age (27.2 vs. 30.1 years, p < 0.01).ConclusionWaterpipe use was associated with metabolic syndrome and its components, especially among former users potentially due to higher intensity and earlier initiation of use.

OBJECTIVE:Despite the implementation of the WHO Framework Convention on Tobacco Control (FCTC) program in Iran, the regulation of second-hand smoke (SHS) exposure-an often-overlooked hazard-, still requires improvement. We employed a multi-center case-control study to investigate the association between exposure to secondhand smoke (SHS) from various tobacco products (cigarettes, water-pipes, pipes, and chopogh), opium use, and the risk of lung cancer. METHOD:We included 627 lung cancer cases and 3477 controls. Exposure to SHS tobacco and SHS opium was collected through a questionnaire. We used mixed-model logistic regressions to estimate odds ratios (ORs) and 95% confidence intervals (CI). RESULT:Among the overall population exposed to second-hand tobacco smoke (SHTS), the odds ratio (OR) compared to those never exposed was 1.35 (95% CI: 1.08-1.71). Never smokers who were ever exposed to second-hand tobacco smoke (SHTS) had 1.69-fold risk of lung cancer compared to those who were never exposed (95% CI: 1.13-2.52). Exposure to SHTS between 2-3 per day (OR = 2.27, 95% CI: 1.13-4.53) and more than three hours per day (OR = 2.29, 95% CI: 1.20-4.37) can increase the risk of lung cancer compared with the no exposure group (P-trend <0.01). We did not observe any association between exposure to second-hand opium smoke (SHOS) and the risk of lung cancer, either in the overall population or among never-smokers. CONCLUSION:Our study estimates the impact of second-hand tobacco smoke (SHTS) on lung cancer risk in both the overall population and never-smokers. Additional studies are required to evaluate the association between exposure to second-hand smoke from opium and other type of tobacco, including water-pipe and the risk of lung cancer.

Introduction: Several studies have linked cardiovascular disease (CVD) to dietary intake of a few minerals, although the link is still unclear, and the findings may not apply to various populations. In a prospective study in a Middle Eastern population, we aimed to assess the relationship between dietary intakes of calcium, selenium, zinc, iron, magnesium, and copper and the risk of CVD mortality. Methods: We used data from the Golestan Cohort Study, which has followed 50,045 participants aged 40-75 years since 2004. We excluded subjects reporting extreme intakes of total energy and a positive history of cancer, CVD, or diabetes at baseline. Mineral intake was estimated from the baseline food frequency questionnaire. Supplement use was not common in this population. Mineral intakes were adjusted by the nutrient density method. We used Cox proportional hazards models to estimate hazards ratio (HR) and 95% confidence intervals (CI) for cardiovascular mortality using the lowest quintile of intake as a reference group for each mineral with adjustment for potential confounders. Results: We analyzed 41,863 subjects that had a mean age of 51.5+8.7 years at baseline . During 579,339 person-years of follow-up (median: 14.1 Years), 3,065 (7.22%) participants died due to CVD. Calcium was the only mineral with a mean intake below the US Recommended Dietary Allowance. We observed significant associations between calcium intake (HR Q5 vs Q1 =0.82, 95% CI=0.73-0.93), selenium intake (HR Q5 vs Q1 =1.14, 95% CI=1.01-1.29), and CVD mortality (P-values <0.05). We observed no statistically significant associations with zinc (HR Q5 vs Q1 =1.10, 95% CI=0.98-1.24), iron (HR Q5 vs Q1 =1.08, 95% CI=0.96-1.22), magnesium (HR Q5 vs Q1 =1.01, 95% CI=0.90-1.14), or copper (HR Q5 vs Q1 =1.11, 95% CI=0.99-1.26) intake and CVD mortality. When modeled as continuous linear variables, iron and copper intake were associated greater risk of CVD mortality (P-values<0.05). Conclusion: Dietary calcium intake was associated with decreased, whereas selenium and possibly copper intake were associated with increased risk of CVD mortality in this Middle Eastern population.

AbstractBackground:Limited data exist for the association between bladder cancers and waterpipe smoking, an emerging global public health concern.Methods:We used the IROPICAN database in Iran and used multivariable logistic regression, adjusting for cigarette smoking, opium use, and other confounding factors. In addition, we studied the association between exclusive waterpipe smoking and bladder cancer.Results:We analyzed 717 cases and 3,477 controls and a subset of 215 patients and 2,145 controls who did not use opium or cigarettes. Although the OR adjusted for opium, cigarettes, and other tobacco products was 0.92 [95% confidence interval (CI), 0.69–1.20], we observed a statistically significant elevated risk in exclusive waterpipe smokers (OR = 1.78; 95% CI, 1.16–2.72) compared with non-users of opium or any tobacco. Associations were strongest for smoking more than two heads/day (OR = 2.25; 95% CI, 1.21–4.18) and for initiating waterpipe smoking at an age less than 20 (OR = 2.73; 95% CI, 1.11–6.72). The OR for urothelial bladder cancer was higher in ex-smokers (OR = 2.35; 95% CI, 1.24–4.42) than in current smokers (OR = 1.52; 95% CI, 0.72–3.15). All observed associations were consistently higher for urothelial histology.Conclusions:Waterpipe smoking may be associated with an increased risk of bladder cancer, notably among individuals who are not exposed to cigarette smoking and opium.Impact:The study provides compelling evidence that waterpipe smoking is a confirmed human carcinogen, demanding action from policymakers.See related In the Spotlight, p. 461

In addition to Helicobacter pylori (H. pylori) infection eradication, some medications, including aspirin, metformin, and statins, have been suggested to have protective effects against gastric cancer (GC) development in observational studies. We launched the Ardabil gastric cancer randomized placebo-controlled prevention trial (AGCPT) to evaluate the effectiveness of long-term low-dose aspirin use for the prevention of development and mortality of GC after H. pylori eradication. AGCPT is a prospective population-based double-blind, randomized clinical trial. The study sample was targeted at 21,000 participants aged from 35 to 70 years old, both sexes, in Ardabil, a province in northwest Iran with relatively high rates of GC incidence and mortality. All eligible participants were initially tested for H. pylori infection using a H. pylori stool antigen test. Participants with positive tests undergo H. pylori eradication by standard treatment regimens. All participants with a negative test and those with a positive test with a subsequent confirmed H. pylori eradication test were entered into the intervention phase. In the intervention phase, participants were allocated randomly into either the treatment (daily oral consumption of 81 mg enteric-coated aspirin tablets) arm or the control (placebo) arm using permuted balanced blocks. Subjects will be followed for an average period of 10 years to evaluate the incidence and mortality rates of GC. In addition to preventing other diseases like cardiovascular events, aspirin may prevent GC incidence and mortality. AGCPT will investigate the difference between the two study arms in the proportion of the cumulative incidence and mortality rates of GC. The study’s results may help policymakers and researchers update the strategies for GC prevention. This trial with the registry name of “The effect of Low-dose Aspirin in the Prevention of Gastric Cancer” was registered in the Iranian Registry of Clinical Trials, IRCT.ir, under the identifier IRCT201105082032N3. Registered on April 21, 2017.

Objectives: This study investigated the association between lung cancer and waterpipe smoking, which is an emerging global public health concern. Study design: Multicentre case-control study. Methods: This study included 627 cases and 3477 controls from the Iranian Study of Opium and Cancer (IROPICAN) study, which was conducted between 2017 and 2020. One frequency-matched control for each lung cancer patient was selected by age, gender and residential place; however, this study used controls of four cancer types in the analyses. The multivariable logistic regression model estimated the odds ratio (OR) and 95% confidence intervals (CIs). Additional analyses were performed among 181 lung cancer cases and 2141 controls who were not cigarette smokers or opium or nass/pipe users. Results: The odds of lung cancer were higher among waterpipe smokers than never-smokers (OR = 1.3, 95% CI: 1.0-1.7). Results showed a higher OR of lung cancer for those who smoked the waterpipe daily (OR = 2.1, 95% CI: 1.4-3.0), smoked more than two heads per day (OR = 2.7, 95% CI: 1.8-4.0), had smoked for >20 years (OR = 1.9, 95% CI: 1.3-2.7), smoked more than 20 head-years (OR = 2.8, 95% CI: 1.9-4.1) and initiated smoking before the age of 30 years (OR = 1.7, 95% CI: 1.1-2.5). The association was only statistically significant for squamous cell carcinomas (OR = 1.8, 95% CI 1.2-2.7). Furthermore, this study observed a higher OR of lung cancer among exclusive waterpipe smokers (OR = 2.3, 95% CI: 1.6, 3.5). Conclusions: Waterpipe smoking was associated with an increased risk of lung cancer. The association was stronger with higher frequency, duration and intensity of exposure to waterpipe smoking. The association increases in exclusive waterpipe smokers, which is likely due to controlling for residual confounding by cigarette smoking and opium consumption, and higher exposure levels in this subpopulation.