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Objectives: To 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). Methods: We 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). Results: Among 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). Conclusion: Waterpipe use was associated with metabolic syndrome and its components, especially among former users potentially due to higher intensity and earlier initiation of use. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Poor oral health has been linked to various systemic diseases, including multiple cancer types, but studies of its association with lung cancer have been inconclusive. Methods: We examined the relationship between dental status and lung cancer incidence and mortality in the Golestan Cohort Study, a large, prospective cohort of 50,045 adults in northeastern Iran. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between three dental health measures (i.e., number of missing teeth; the sum of decayed, missing, or filled teeth (DMFT); and toothbrushing frequency) and lung cancer incidence or mortality with adjustment for multiple potential confounders, including cigarette smoking and opium use. We created tertiles of the number of lost teeth/DMFT score in excess of the loess adjusted, age- and sex-specific predicted numbers, with subjects with the expected number of lost teeth/DMFT or fewer as the reference group. Results: During a median follow-up of 14 years, there were 119 incident lung cancer cases and 98 lung cancer deaths. Higher DMFT scores were associated with a progressively increased risk of lung cancer (linear trend, p = 0.011). Compared with individuals with the expected DMFT score or less, the HRs were 1.27 (95% CI: 0.73, 2.22), 2.15 (95% CI: 1.34, 3.43), and 1.52 (95% CI: 0.81, 2.84) for the first to the third tertiles of DMFT, respectively. The highest tertile of tooth loss also had an increased risk of lung cancer, with a HR of 1.68 (95% CI: 1.04, 2.70) compared with subjects with the expected number of lost teeth or fewer (linear trend, p = 0.043). The results were similar for lung cancer mortality and did not change substantially when the analysis was restricted to never users of cigarettes or opium. We found no associations between toothbrushing frequency and lung cancer incidence or mortality. Conclusion: Poor dental health indicated by tooth loss or DMFT, but not lack of toothbrushing, was associated with increased lung cancer incidence and mortality in this rural Middle Eastern population. [ABSTRACT FROM AUTHOR]

Introduction: Waterpipe smoking has become increasingly popular in Western countries, particularly among young individuals. This study aims to identify the factors influencing waterpipe smoking by focusing on consumption patterns. Methods: We utilized data from a multicenter case–control study (IROPICAN) conducted in Iran. Multivariate logistic regression estimated the adjusted odds ratio and 95% confidence intervals as a measure of association between waterpipe smoking and different factors. Results: Among 3,477 subjects were included, 11.8% were waterpipe smokers. Most of <50  years old smokers were occasional (80%), while daily smokers were often >50  years (85%). Around 59% of occasional users started it before 30  years old. Low education, low SES, alcohol consumption, cigarette smoking, secondhand smoke exposure, and opium use were associated with waterpipe smoking. Stratified analysis by frequency pattern showed an association between occasional smoking with age 0.97 (0.96–0.98), university degree 0.36 (0.17–0.76), urban dwellers 1.40 (1.06–1.86) and between high SES and daily smoking 0.34 (0.17–0.69). Conclusion: Our results offer valuable information to policymakers for developing waterpipe smoking control measures. The occasional waterpipe smoking results may be generalized to the younger people in Western countries. [ABSTRACT FROM AUTHOR]

Background. Benzene is a known human carcinogen. Human exposure to benzene can be assessed by measuring trans, trans-muconic acid (MUCA) in urine. Golestan Province in northeastern Iran has been reported to have high incidence of esophageal cancer linked to the use of tobacco products. This manuscript evaluates the urinary MUCA concentrations among the participants of the Golestan Cohort Study (GCS). Methods. We analyzed MUCA concentration in 177 GCS participants' urine samples and performed nonparametric pairwise multiple comparisons to determine statistically significant difference among six different product use groups. Mixed effects model was fitted on 22 participants who exclusively smoked cigarette and 51 participants who were classified as nonusers. The urinary MUCA data were collected at the baseline and approximately five years later, and intraclass correlation coefficient (ICC) was calculated from the model. Results. Compared with nonusers, tobacco smoking was associated with higher urinary MUCA concentrations. Based on the nonparametric test of pairwise multiple comparisons, MUCA concentrations among participants who smoked combusted tobacco products were statistically significantly higher compared to nonusers. Urinary MUCA collected five years apart from the same individuals showed moderate reliability (ICC = 0.41), which was expected given the relatively short half-life (∼6 h) of MUCA. Conclusion. Our study revealed that tobacco smoke was positively associated with increased levels of urinary MUCA concentration, indicating that it is a significant source of benzene exposure among GCS participants. [ABSTRACT FROM AUTHOR]

Opiates can affect glucose metabolism and obesity, but no large prospective study (to our knowledge) has investigated the association between long-term opium use, body mass index (BMI; weight (kg)/height (m)2), and incident type 2 diabetes mellitus (T2DM). We analyzed prospective data from 50,045 Golestan Cohort Study participants in Iran (enrollment: 2004–2008). After excluding participants with preexisting diseases, including diabetes, we used adjusted Poisson regression models to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for T2DM in opium users compared with nonusers, using mediation analysis to assess the BMI-mediated association of opium use with incident T2DM. Of 40,083 included participants (mean age = 51.4 (standard deviation, 8.8) years; 56% female), 16% were opium users (median duration of use, 10 (interquartile range), 4–20) years). During follow-up (until January 2020), 5,342 incident T2DM cases were recorded, including 8.5% of opium users and 14.2% of nonusers. Opium use was associated with an overall decrease in incident T2DM (IRR = 0.83, 95% CI: 0.75, 0.92), with a significant dose-response association. Most (84.3%) of this association was mediated by low BMI or waist circumference, and opium use did not have a direct association with incident T2DM (IRR = 0.97, 95% CI: 0.87, 1.08). Long-term opium use was associated with lower incidence of T2DM, which was mediated by low body mass and adiposity. [ABSTRACT FROM AUTHOR]

Opium use has been associated with an increased risk of cancers of the lung, oesophagus, and pancreas, and it was recently classified by the International Agency for Cancer Research as carcinogenic to humans. It is not clear whether opium also increases the risk of colorectal cancer (CRC). The aim of our study was to assess the association between various metrics of opium use and the risk of CRC. This case-referent study from seven provinces in Iran comprised 848 CRC cases and 3215 referents. Data on opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure odds ratios (OR) adjusted for age, gender, province, marital status, family history of CRC-linked cancers, consumption of red meat, fruits and vegetables, body shape, occupational physical activity, and socioeconomic status. Regular opium consumption was not associated with the risk of CRC (OR 0.9, 95% confidence interval, CI: 0.7, 1.2) compared to subjects who never used opium. However, frequent opium use more than twice a day was associated with an increased risk of CRC compared to non-users of opium (OR: 2.0, 95% CI: 1.1, 3.8; p for quadratic trend 0.008). There seems to be no overall association between opium use and CRC, but the risk of CRC might be increased among persons who use opium many times a day. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) is increasing in low- and middle-income countries, likely due to changing lifestyle habits, including diet. We found that a higher total choline intake was associated with an elevated risk of CRC, as well as glycerophosphocholine (GPC) and sphingomyelin (SM). Conversely, betaine intake was associated with a decreased risk of CRC. Consequently, it is possible to focus on the intake of betaine sources and manage the use of animal products as references for SM or other choline types with risks of CRC. Background: Colorectal cancer (CRC) is increasing in low- and middle-income countries, likely due to changing lifestyle habits, including diet. We aimed to investigate the relationship between dietary betaine, choline, and choline-containing compounds and CRC risk. Methods: We analyzed data from a case–control study, including 865 CRC cases and 3206 controls from Iran. Detailed information was collected by trained interviewers using validated questionnaires. The intake of free choline, phosphocholine (Pcho), glycerophosphocholine (GPC), phosphatidylcholine (PtdCho), and sphingomyelin (SM), as well as of betaine was estimated from food frequency questionnaires and categorized into quartiles. The odds ratios (OR) and 95% confidence intervals (CI) of CRC for choline and betaine quartiles were calculated using multivariate logistic regression by adjusting for potential confounders. Results: We observed excess risk of CRC in the highest versus lowest intake of total choline (OR = 1.23, 95% CI 1.13, 1.33), GPC (OR = 1.13, 95% CI 1.00, 1.27), and SM (OR = 1.14, 95% CI 1.01, 1.28). The intake of betaine exerted an inverse association with CRC risk (OR = 0.91, 95% CI 0.83, 0.99). There was no association between free choline, Pcho, PtdCho, and CRC. Analyses stratified by gender showed an elevated OR of CRC in men for SM intake OR = 1.20, 95% CI 1.03, 1.40) and a significantly decreased CRC risk in women for betaine intake (OR = 0.84, 95% CI 0.73, 0.97). Conclusion: Dietary modifications leading to an increase in betaine sources and managing the use of animal products as references for SM or other choline types might contribute to decreasing the risk of CRC. [ABSTRACT FROM AUTHOR]

Red meat and processed meat are associated with some gastrointestinal cancers. Our study aims to investigate the association of different meat types with esophageal and gastric cancer (EC, GC) in a high‐risk population. The Golestan Cohort Study (GCS) is a population‐based cohort of 50 045 individuals aged 40 to 75 from northeast Iran. Detailed data on different exposures were collected using validated questionnaires. We considered quintiles of meat consumption, using grams and density (g/1000 kcal/day). We calculated intake of red, processed, organ and white meat, as well as total red meat, including the first three. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between meat types and cancer. During 12 years of follow‐up, out of 49 585 participants (57.4% women), 369 developed EC (48.2% women) and 368 developed GC (27.5% women), including 309 esophageal squamous cell, 20 esophageal adenocarcinomas, 216 cardia and 95 non‐cardia GC. No association was found for EC except for red meat among females (HR for one quintile increase 1.13, 95% CI = 1.00‐1.27). The risk of GC increased for intake of total red meat (HR 1.08, 95% CI = 1.00‐1.17) and red meat separately (HR 1.09, 95% CI = 1.00‐1.18). The HR for red meat and non‐cardia GC was 1.23 (95% CI = 1.02‐1.48). No associations were observed for other types of meat. In conclusion, in this high‐risk population red meat intake is associated with GC, but not EC, suggesting a substantial role of this modifiable factor in determining the burden of GC. [ABSTRACT FROM AUTHOR]

Background: Environmental exposures account for a growing proportion of global mortality. Large cohort studies are needed to characterize the independent impact of environmental exposures on mortality in low-income settings. Methods: We collected data on individual and environmental risk factors for a multiethnic cohort of 50,045 individuals in a low-income region in Iran. Environmental risk factors included: ambient fine particular matter air pollution; household fuel use and ventilation; proximity to traffic; distance to percutaneous coronary intervention (PCI) center; socioeconomic environment; population density; local land use; and nighttime light exposure. We developed a spatial survival model to estimate the independent associations between these environmental exposures and all-cause and cardiovascular mortality. Findings: Several environmental factors demonstrated associations with mortality after adjusting for individual risk factors. Ambient fine particulate matter air pollution predicted all-cause mortality (per μg/m3, HR 1.20, 95% CI 1.07, 1.36) and cardiovascular mortality (HR 1.17, 95% CI 0.98, 1.39). Biomass fuel use without chimney predicted all-cause mortality (reference = gas, HR 1.23, 95% CI 0.99, 1.53) and cardiovascular mortality (HR 1.36, 95% CI 0.99, 1.87). Kerosene fuel use without chimney predicted all-cause mortality (reference = gas, HR 1.09, 95% CI 0.97, 1.23) and cardiovascular mortality (HR 1.19, 95% CI 1.01, 1.41). Distance to PCI center predicted all-cause mortality (per 10km, HR 1.01, 95% CI 1.004, 1.022) and cardiovascular mortality (HR 1.02, 95% CI 1.004, 1.031). Additionally, proximity to traffic predicted all-cause mortality (HR 1.13, 95% CI 1.01, 1.27). In a separate validation cohort, the multivariable model effectively predicted both all-cause mortality (AUC 0.76) and cardiovascular mortality (AUC 0.81). Population attributable fractions demonstrated a high mortality burden attributable to environmental exposures. Interpretation: Several environmental factors predicted cardiovascular and all-cause mortality, independent of each other and of individual risk factors. Mortality attributable to environmental factors represents a critical opportunity for targeted policies and programs. [ABSTRACT FROM AUTHOR]

Purpose: The lung cancer incidence in Iran has increased almost ten times over the past three decades. In addition to the known causes such as smoking and certain occupational exposure, dietary quality has been suggested to play a role in lung cancer. We aim to explore the association between dietary pattern and lung cancer risk among a Middle East population. Methods: Data came from Golestan Cohort Study which included 48,421 participants with 136 lung cancer cases diagnosed during a median follow-up of 12 years. Multivariable Cox proportional hazards regression models were used to calculate the HRs and 95% CI of lung cancer risk by tertile of the four dietary index scores—the Health Eating Index (HEI)-2015, the Alternative Health Eating Index (AHEI)-2010, the Alternative Mediterranean Diet (AMED), and the Dietary Approach to Stop Hypertension (DASH)-Fung. Results: A higher DASH-Fung score was inversely associated with risk of lung cancer after adjusting for potential confounders (tertile three vs. tertile one: HR = 0.59 (0.38–0.93); p for trend = 0.07), and pinteraction with smoking was 0.46. Similar findings were observed among current smokers with the HEI-2015 score (tertile three vs. tertile one: HR = 0.22 (0.08–0.60): p for trend < 0.01), and pinteraction between smoking and the HEI-2015 score was 0.03. Conclusion: In the GCS, consuming a diet more closely aligned with the DASH diet was associated with a reduced risk of lung cancer, which appeared to be independent of smoking status. There was also an inverse link between the HEI-2015 score and lung cancer risk among current smokers. Our finding is particularly important for the Middle East population, as diet may play an important role in cancer prevention and overall health. [ABSTRACT FROM AUTHOR]

Background: Many diabetic individuals use prescription and non-prescription opioids and opiates. We aimed to investigate the joint effect of diabetes and opiate use on all-cause and cause-specific mortality.Methods: Golestan Cohort study is a prospective population-based study in Iran. A total of 50 045 people-aged 40-75, 28 811 women, 8487 opiate users, 3548 diabetic patients-were followed during a median of 11.1 years, with over 99% success follow-up. Hazard ratio and 95% confidence intervals (HRs, 95% CIs), and preventable death attributable to each risk factor, were calculated.Results: After 533 309 person-years, 7060 deaths occurred: 4178 (10.8%) of non-diabetic non-opiate users, 757 (25.3%) diabetic non-users, 1906 (24.0%) non-diabetic opiate users and 219 (39.8%) diabetic opiate users. Compared with non-diabetic non-users, HRs (95% CIs) for all-cause mortality were 2.17 (2.00-2.35) in diabetic non-opiate users, 1.63 (1.53-1.74) in non-diabetic opiate users and 2.76 (2.40-3.17) in diabetic opiate users. Among those who both had diabetes and used opiates, 63.8% (95% CI: 58.3%-68.5%) of all deaths were attributable to these risk factors, compared with 53.9% (95% CI: 50%-57.4%) in people who only had diabetes and 38.7% (95% CI: 34.6%-42.5%) in non-diabetic opiate users. Diabetes was more strongly associated with cardiovascular than cancer mortality. The risk of early mortality in known cases of diabetes did not depend on whether they started opiate use before or after their diagnosis.Conclusions: Using opiates is detrimental to the health of diabetic patients. Public awareness about the health effects of opiates, and improvement of diabetes care especially among individuals with or at risk of opiate use, are necessary. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is one of the world's largest health epidemics, and its management is a major challenge worldwide. The aim of this 10-year follow-up study was to assess the most important predictors of MetS persistence among an Iranian adult population. Methods: In this cohort study, 887 out of 2000 participants with MetS aged 20-74 years in the central part of Iran were followed-up for about 10 years from 2005-2006 to 2015-2016. MetS was defined based on the criteria of NCEP-ATP III adopted for the Iranian population. Cox proportional hazards regression was conducted to evaluate the predictors of MetS persistence in crude- and multivariate-adjusted models. Results: Our analyses showed that 648 out of 887 participants (73%) completed the follow-up and 565 (87.2%) of them had persistence of MetS after 10-year follow-up. There was a significant association between age, weight, body mass index, triglyceride, and waist circumference in participants who had MetS compared to those without MetS after 10-year follow-up (P < 0.05). There was a direct association between increases in the mean changes of systolic/diastolic blood pressure, waist circumference, and low HDL-C and risk of MetS persistence after adjusting the model for sex and age in the total population (Ptrend < 0.05). The trends were the same for women except in diastolic blood pressure. After adjustment for potential confounders, the risk of MetS persistence in men was significantly higher than women (HR = 1.98, 95% CI: 1.38-2.85, Ptrend = 0.001). Conclusions: Most of the risk factors of MetS were positively associated with persistence of MetS. Therefore, modification of lifestyle is recommended to reduce MetS. [ABSTRACT FROM AUTHOR]

Previous studies have reported an association between hot tea drinking and risk of esophageal cancer, but no study has examined this association using prospectively and objectively measured tea drinking temperature. We examined the association of tea drinking temperature, measured both objectively and subjectively at study baseline, with future risk of esophageal squamous cell carcinoma (ESCC) in a prospective study. We measured tea drinking temperature using validated methods and collected data on several other tea drinking habits and potential confounders of interest at baseline in the Golestan Cohort Study, a population‐based prospective study of 50,045 individuals aged 40–75 years, established in 2004–2008 in northeastern Iran. Study participants were followed‐up for a median duration of 10.1 years (505,865 person‐years). During 2004–2017, 317 new cases of ESCC were identified. The objectively measured tea temperature (HR 1.41, 95% CI 1.10–1.81; for ≥60°C vs. <60°C), reported preference for very hot tea drinking (HR 2.41, 95% CI 1.27–4.56; for "very hot" vs. "cold/lukewarm"), and reported shorter time from pouring tea to drinking (HR 1.51, 95% CI 1.01–2.26; for <2 vs. ≥6 min) were all associated with ESCC risk. In analysis of the combined effects of measured temperature and amount, compared to those who drank less than 700 ml of tea/day at <60°C, drinking 700 mL/day or more at a higher‐temperature (≥60°C) was consistently associated with an about 90% increase in ESCC risk. Our results substantially strengthen the existing evidence supporting an association between hot beverage drinking and ESCC. What's new? Previous studies have indicated that hot tea may increase the risk of esophageal cancer. In this large, prospective study, the authors found that drinking hot tea is indeed associated with an increased risk of esophageal squamous cell carcinoma (ESCC). Furthermore, a preference for "very hot" tea more than doubled this risk. It may thus be a reasonable public‐health measure to extrapolate these results to all types of beverages, and to advise the public to wait for beverages to cool to <60°C before consumption. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background The associations between dietary indices and mortality have not been evaluated in populations from the Middle East, which have different dietary patterns compared to the US and Europe. In this study, we evaluated the association between six dietary indices and mortality in the Golestan Cohort Study (GCS) in Iran, which is the largest prospective study in the Middle East with 50,045 participants. Methods The six dietary indices, namely the Healthy Eating Index (HEI-2015), Alternative Healthy Eating Index (AHEI-2010), Alternative Mediterranean Diet (AMED), Dietary Approach to Stop Hypertension created by Fung (DASH-Fung) and Mellen (DASH-Mellen), and the World Cancer Research Fund (WCRF/AICR) index, were applied to data from a food frequency questionnaire, computed and divided into quintiles. Adjusted Cox models were used to estimate hazards ratio (HR) and 95% confidence intervals (CI) for overall and cause-specific mortality, using the lowest quintile as a reference group. Results Among 42,373 participants included in the current analyses, 4424 subjects died during 10.6 years of follow-up. Participants with the highest quintile dietary scores, compared with the lowest quintile dietary scores, had significantly decreased overall mortality in the AHEI-2010, AMED, DASH-Fung, and WCRF/AICR indices (HR 0.88, 95% CI = 0.80–0.97; 0.80, 0.70–0.91; 0.77, 0.70–0.86; and 0.79, 0.70–0.90, respectively). A reduced cardiovascular mortality was found for high AHEI-2010 and DASH-Fung scores (17% and 23%, respectively), and a reduced cancer mortality for high HEI-2015, AMED, and DASH-Fung scores (21, 37 and 25%, respectively). Conclusion Various indices of dietary quality are inversely associated with overall mortality, and selectively with cancer and cardiovascular mortality in the GCS, which contribute to the generalizability and validity of dietary guidelines. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested that opium use may increase mortality from cancer and cardiovascular diseases. However, no comprehensive study of opium use and mortality from respiratory diseases has been published. We aimed to study the association between opium use and mortality from respiratory disease using prospectively collected data.Methods: We used data from the Golestan Cohort Study, a prospective cohort study in northeastern Iran, with detailed, validated data on opium use and several other exposures. A total of 50 045 adults were enrolled from 2004 to 2008, and followed annually until June 2015, with a follow-up success rate of 99%. We used Cox proportional hazard regression models to evaluate the association between opium use and outcomes of interest.Results: During the follow-up period, 331 deaths from respiratory disease were reported (85 due to respiratory malignancies and 246 due to non-malignant aetiologies). Opium use was associated with an increased risk of death from any respiratory disease (adjusted HR 95% CI 3.13 (2.42 to 4.04)). The association was dose-dependent with a HR of 3.84 (2.61 to 5.67) for the highest quintile of cumulative opium use versus never use (Ptrend<0.001). The HRs (95% CI) for the associations between opium use and malignant and non-malignant causes of respiratory mortality were 1.96 (1.18 to 3.25) and 3.71 (2.76 to 4.96), respectively.Conclusions: Long-term opium use is associated with increased mortality from both malignant and non-malignant respiratory diseases. [ABSTRACT FROM AUTHOR]

We investigated the association between dairy product consumption and all-cause, cardiovascular disease (CVD), and cancer mortality in the Golestan Cohort Study, a prospective cohort study launched in January 2004 in Golestan Province, northeastern Iran. A total of 42,403 men and women participated in the study and completed a diet questionnaire at enrollment. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. We documented 3,291 deaths (1,467 from CVD and 859 from cancer) during 11 years of follow-up (2004-2015). The highest quintile of total dairy product consumption (versus the lowest) was associated with 19% lower all-cause mortality risk (hazard ratio (HR) = 0.81, 95% confidence interval (CI): 0.72, 0.91; Ptrend = 0.006) and 28% lower CVD mortality risk (HR = 0.72, 95% CI: 0.60, 0.86; Ptrend = 0.005). High consumption of low-fat dairy food was associated with lower risk of all-cause (HR = 0.83, 95% CI: 0.73, 0.94; Ptrend = 0.002) and CVD (HR = 0.74, 95% CI: 0.61, 0.89; Ptrend = 0.001) mortality. We noted 11% lower all-cause mortality and 16% lower CVD mortality risk with high yogurt intake. Cheese intake was associated with 16% lower all-cause mortality and 26% lower CVD mortality risk. Higher intake of high-fat dairy food and milk was not associated with all-cause or CVD mortality. Neither intake of individual dairy products nor intake of total dairy products was significantly associated with overall cancer mortality. High consumption of dairy products, especially yogurt and cheese, may reduce the risk of overall and CVD mortality. [ABSTRACT FROM AUTHOR]

Background: A number of prospective studies have observed inverse associations between nut consumption and chronic diseases. However, these studies have predominantly been conducted in Western countries, where nut consumption tends to be more common among individuals with healthier lifestyles. It is important to examine the association in other parts of the world, and particularly among populations with different patterns of disease, socioeconomic status, lifestyles and disease risk factors. Our objective was to examine the association between nut consumption and mortality in a population whose nut consumption does not track with a healthy lifestyle.Methods: We examined the association between nut consumption and all-cause and cause-specific mortality in the 50 045 participants of the Golestan Cohort Study. Participants were aged 40 and older at baseline in 2004, and have been actively followed since that time. Dietary data were collected using a validated semi-quantitative food frequency questionnaire that was administered at baseline.Results: During 349 677 person-years of follow-up, 3981 cohort participants died, including 1732 women and 2249 men. Nut consumption was associated inversely with all-cause mortality. The pooled multivariate adjusted hazard ratios for death among participants who ate nuts, as compared with those who did not, were 0.89 [95% confidence interval (CI), 0.82-0.95] for the consumption of less than one serving of nuts per week, 0.75 (95% CI, 0.67-0.85) for one to less than three servings per week and 0.71 (95% CI, 0.58-0.86) for three or more servings per week ( P < 0.001 for trend). Among specific causes, significant inverse associations were observed between nut consumption and deaths due to cardiovascular disease, all cancers and gastrointestinal cancers.Conclusions: This study provides evidence for an inverse association between nut consumption and mortality in a developing country, where nut consumption does not track with a healthy lifestyle. Further work is needed to establish the underlying mechanisms responsible for this association. [ABSTRACT FROM AUTHOR]

Background: Refined grains and white rice have been associated with elevated risk of type 2 diabetes mellitus (T2DM). In this study, we sought to quantify the effect of white rice intake on incident T2DM in two prospective population-based cohort studies from Iran, where white rice is one of the main staple.Methods: We used follow-up data from 9,182 participants from Golestan Cohort Study (GCS, 2004-2007, conducted mainly in rural areas) and 2,173 from Tehran Lipid and Glucose Study (TLGS, 2004-2006) who did not have T2DM and other chronic diseases at baseline. Diet was assessed using validated food frequency questionnaires. Multivariable logistic regression models were used to estimate adjusted odds ratios (ORs) for incident T2DM.Results: We documented 902 new cases of T2DM in GCS and 81 in TLGS. Age-standardized cumulative incidence of T2DM was 9.9% in Golestan and 8.0% in Tehran. Daily white rice intake was significantly higher among residents of Tehran compared to Golestan (median daily intake: 250 vs. 120 grams; P-value < 0.001). After adjustment for potential confounders, there was no significant association between daily white rice intake and incident T2DM in GCS. In TLGS, the adjusted OR (95% confidence interval (CI)) was 2.1 (1.1, 3.9) comparing participants with daily white rice intake of >250 grams/day to those with <250.Conclusions: We observed an increased lieklihood of T2DM associated with high white rice intake among residents of Tehran and no association in Golestan. Our findings, if further supported by other studies, have important public health implications especially for countries where white rice is a major staple and diabetes is increasing rapidly incidence is high. Further research is needed to investigate lack of an association between lower levels of white rice intake and T2DM. [ABSTRACT FROM AUTHOR]

Background: Dietary factors have been hypothesized to affect the risk of esophageal cancer via different mechanisms, but the intake of minerals is understudied and the evidence is conflicting. Objective: The objective was to evaluate the associations of dietary intake of minerals with risk of esophageal squamous cell carcinoma (ESCC). Design: We used data from the Golestan Cohort Study, which was launched in a high-risk region for esophageal cancer in Iran. Participants were enrolled in 2004-2008 and were followed to 2014. Intakes of minerals were assessed with a validated food-frequency questionnaire. A Cox proportional hazards model was used to estimate HRs and 95% CIs of ESCC for dietary intakes of selected minerals. Results: We identified 201 ESCC cases among 47,405 subjects. Calcium intake was significantly inversely associated with the risk of ESCC (HR per 100-mg/d increase: 0.88; 95% CI: 0.81, 0.96; P = 0.005; quartile 4 vs. quartile 1 HR: 0.49; 95% CI: 0.29, 0.82; P-trend = 0.013). Zinc intake was also inversely associated with ESCC, but the quartile association did not reach significance (HR per 1-mg/d increase: 0.87; 95% CI: 0.77, 0.98; P = 0.027; quartile 4 vs. quartile 1 HR: 0.56; 95% CI: 0.28, 1.12; P-trend = 0.097). The relations between dietary intakes of selenium, magnesium, and copper and risk of ESCC were nonlinear (P-nonlinear trend = 0.001, 0.016, and 0.029, respectively). There was no relation between dietary intake of manganese and the risk of ESCC. Conclusion: The results suggest that higher intakes of calcium and zinc are associated with a lower risk of ESCC in a high-risk region of Iran. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases (CVD) are becoming major causes of death in developing countries. Risk scoring systems for CVD are needed to prioritize allocation of limited resources. Most of these risk score algorithms have been based on a long array of risk factors including blood markers of lipids. However, risk scoring systems that solely use office-based data, not including laboratory markers, may be advantageous. In the current analysis, we validated the office-based Framingham risk scoring system in Iran. Methods: The study used data from the Golestan Cohort in North-East of Iran. The following risk factors were used in the development of the risk scoring method: sex, age, body mass index, systolic blood pressure, hypertension treatment, current smoking, and diabetes. Cardiovascular risk functions for prediction of 10-year risk of fatal CVDs were developed. Results: A total of 46,674 participants free of CVD at baseline were included. Predictive value of estimated risks was examined. The resulting Area Under the ROC Curve (AUC) was 0.774 (95% CI: 0.762-0.787) in all participants, 0.772 (95% CI: 0.753-0.791) in women, and 0.763 (95% CI: 0.747-0.779) in men. AUC was higher in urban areas (0.790, 95% CI: 0.766-0.815). The predicted and observed risks of fatal CVD were similar in women. However, in men, predicted probabilities were higher than observed. Conclusion: The AUC in the current study is comparable to results of previous studies while lipid profile was replaced by body mass index to develop an office-based scoring system. This scoring algorithm is capable of discriminating individuals at high risk versus low risk of fatal CVD. [ABSTRACT FROM AUTHOR]

Cooking methods have been implicated in the etiology of gastrointestinal cancers, reflecting exposure to potential carcinogens as results of cooking. We used a validated food frequency questionnaire and a pretested cooking method questionnaire in 3 groups: 40 esophageal squamous cell carcinoma (ESCC) cases from a high-risk area in northeast of Iran, 40 healthy subjects from the same high-risk area, and 40 healthy subjects from a low-risk area in Southern Iran. We compared the frequency of boiling, grilling, and frying, and the frying score among these 3 groups. We also calculated “frying index” by multiplying the frequency of each fried food item by its frying score. Mean frying to boiling ratios were 18.2:1, 12.8:1, and 2.6:1 for cases, high-risk controls, and low-risk controls, respectively (P< 0.01). Reuse of cooking oil for frying was reported in 37.5% of the ESCC cases, 25% of high-risk controls, and 7.5% of low-risk controls (P< 0.001). Frying index was higher in the high-risk than in the low-risk controls (P< 0.001) and in cases than in the high-risk controls (P< 0.05) after adjusting for smoking, opium use, rural residence, education, and ethnicity. High-temperature cooking and frying may be associated with increased risk of ESCC in high-risk areas. [ABSTRACT FROM PUBLISHER]

We conducted this study to examine life-course body size and physical activity in relation to total and cause-specific mortality, which has not previously been studied in the low and middle-income countries in Asia. The Golestan Cohort Study is a population-based cohort in northeastern Iran in which 50,045 people above the age of 40 have been followed since 2004. Participants were shown a validated pictogram to assess body size at ages 15, 30, and the time of recruitment. Information on occupational physical activity at these ages was also collected. Subjects were followed up annually, and cause of death was determined. Cox regression models were adjusted for age at cohort start, smoking, socioeconomic status, ethnicity, place of residence, education, and opium use. Models for body size were also adjusted for physical activity at the same age, and vice versa. During a total of 252,740 person-years of follow-up (mean follow-up duration 5.1 ± 1.3 years) through December 2011, 2,529 of the cohort participants died. Larger body sizes at ages 15 or 30 in both sexes were associated with increased overall mortality. Cancer mortality was more strongly associated with adolescent obesity, and cardiovascular mortality with early adulthood body size. Weight gain between these ages was associated with cardiovascular mortality. Obese adolescents who lost weight still had increased mortality from all medical causes in both sexes. Physical activity during adolescence and early adulthood had no association with mortality, but at cohort baseline higher levels of activity were associated with reduced mortality. Mortality in this Middle-Eastern population was associated with obesity both during adolescence and early adult life. [ABSTRACT FROM AUTHOR]

Objective Water-pipe and smokeless tobacco use have been associated with several adverse health outcomes. However, little information is available on the association between water-pipe use and heart disease (HD). Therefore, we investigated the association of smoking water-pipe and chewing nass (a mixture of tobacco, lime and ash) with prevalent HD. Design Cross-sectional study. Setting Baseline data (collected in 2004-2008) from a prospective population-based study in Golestan Province, Iran. Participants 50 045 residents of Golestan (40- 75 years old; 42.4% men). Main outcome measures ORs and 95% CIs from multivariate logistic regression models for the association of water-pipe and nass use with HD prevalence. Results A total of 3051 (6.1%) participants reported a history of HD, and 525 (1.1%) and 3726 (7.5%) reported ever water-pipe or nass use, respectively. Heavy water-pipe smoking was significantly associated with HD prevalence (highest level of cumulative use vs never use, OR=3.75; 95% CI 1.52 to 9.22; p for trend=0.04). This association persisted when using different cut-off points, when restricting HD to those taking nitrate compound medications, and among never cigarette smokers. There was no significant association between nass use and HD prevalence (highest category of use vs never use, OR=0.91; 95% CI 0.69 to 1.20). Conclusions Our study suggests a significant association between HD and heavy water-pipe smoking. Although the existing evidence suggesting similar biological consequences of water-pipe and cigarette smoking make this association plausible, results of our study were based on a modest number of water-pipe users and need to be replicated in further studies. [ABSTRACT FROM AUTHOR]

Background: Golestan Province in northeastern Iran has one of the highest incidences of esophageal squamous cell carcinoma (ESCC) in the world with rates over 50 per 100,000 person-years in both sexes. We have analyzed TP53 mutation patterns in tumors from this high-risk geographic area in search of clues to the mutagenic processes involved in causing ESCC. Methodology/Principal Findings: Biopsies of 119 confirmed ESCC tumor tissue from subjects enrolled in a case-control study conducted in Golestan Province were analyzed by direct sequencing of TP53 exons 2 through 11. Immunohistochemical staining for p53 was carried out using two monoclonal antibodies, DO7 and 1801. A total of 120 TP53 mutations were detected in 107/119 cases (89.9%), including 11 patients with double or triple mutations. The mutation pattern was heterogeneous with infrequent mutations at common TP53 ''hotspots'' but frequent transversions potentially attributable to environmental carcinogens forming bulky DNA adducts, including 40% at bases known as site of mutagenesis by polycyclic aromatic hydrocarbons (PAHs). Mutations showed different patterns according to the reported temperature of tea consumption, but no variation was observed in relation to ethnicity, tobacco or opium use, and alcoholic beverage consumption or urban versus rural residence. Conclusion/Significance: ESCC tumors in people from Golestan Province show the highest rate of TP53 mutations ever reported in any cancer anywhere. The heterogeneous mutation pattern is highly suggestive of a causative role for multiple environmental carcinogens, including PAHs. The temperature and composition of tea may also influence mutagenesis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the association between polycyclic aromatic hydrocarbon (PAH) exposure in oesophageal epithelial tissue and oesophageal squamous cell carcinoma (ESCC) case status in an ESCC case–control study in a high-risk population in north-eastern Iran. METHODS: Tissue microarrays (TMAs) of non-tumoral oesophageal biopsies from patients with biopsy-proven ESCC and gastrointestinal clinic patients with no endoscopic or biopsy evidence of ESCC (control subjects) in a rural region in north-eastern Iran were immunohistochemically stained. Immunohistochemistry was performed using monoclonal antibodies 8E11 and 5D11 raised against benzo[a]pyrene (B[a]P) diol epoxide (BPDE)-I-modified guanosine and BPDE-I-modified DNA, respectively. Staining intensity was quantified by image analysis and the average staining in three replicates was calculated. The main outcome measure was adjusted ORs with 95% CIs for the association between antibody staining intensity and ESCC case status. RESULTS: Cultured ESCC cells exposed to B[a]P in vitro showed dose-dependent staining with 8E11 but not with 5D11. With 8E11, sufficient epithelial tissue was available in the TMA cores to analyse 91 cases and 103 controls. Compared with the lowest quintile of 8E11 staining in the controls, adjusted ORs for the 2nd to 5th quintiles were 2.42, 5.77, 11.3 and 26.6 (95% CI 5.21 to 135), respectively (p for trend <0.001). With 5D11, 89 cases and 101 controls were analysed. No association between staining and case status was observed (ORs for the 2nd to 5th quintiles were 1.26, 0.88, 1.06 and 1.63 (95% CI 0.63 to 4.21), p for trend=0.40). CONCLUSIONS: Dramatically higher levels of 8E11 staining were observed in non-tumoral oesophageal epithelium from patients with ESCC than from control subjects. This finding strengthens the evidence for a causal role for PAHs in oesophageal carcinogenesis in north-eastern Iran. [ABSTRACT FROM AUTHOR]

Background: Verbal autopsy (VA) is one method to obtain valid estimates of causes of death in the absence of valid medical records. We tested the reliability and validity of a VA questionnaire developed for a cohort study in Golestan Province in northeastern Iran. Method: A modified version of the WHO adult verbal autopsy was used to assess the cause of death in the first 219 Golestan Cohort Study (GCS) subjects who died. The GCS cause of death was determined by two internists who independently reviewed all available medical records. Two other internists (''reviewers'') independently reviewed only the VA answers and classified the cause of death into one of nine general categories; they repeated this evaluation one month later. The reliability of the VA was measured by calculating intra-reviewer and inter-reviewer kappa statistics. The validity of the VA was measured using the GCS cause of death as the gold standard. Results: VA showed both good validity (sensitivity, specificity, PPV, and NPV all above 0.81) and reliability (kappa.0.75) in determining the general cause of death independent of sex and place of residence. The overall multi-rater agreement across four reviews was 0.84 (95%CI: 0.78-0.89). The results for identifying specific cancer deaths were also promising, especially for upper GI cancers (kappa = 0.95). The multi-rater agreement in cancer subgroup was 0.93 (95%CI: 0.85-0.99). Conclusions: VA seems to have good reliability and validity for determining the cause of death in a large-scale adult follow up study in a predominantly rural area of a middle-income country. [ABSTRACT FROM AUTHOR]

Background: Cancer registries in the 1970s showed that parts of Golestan Province in Iran had the highest rate of oesophageal squamous cell carcinoma (OSCC) in the world. More recent studies have shown that while rates are still high, they are approximately half of what they were before, which might be attributable to improved socio-economic status (SES) and living conditions in this area. We examined a wide range of SES indicators to investigate the association between different SES components and risk of OSCC in the region.Methods: Data were obtained from a population-based case-control study conducted between 2003 and 2007 with 300 histologically proven OSCC cases and 571 matched neighbourhood controls. We used conditional logistic regression to compare cases and controls for individual SES indicators, for a composite wealth score constructed using multiple correspondence analysis, and for factors obtained from factors analysis.Results: We found that various dimensions of SES, such as education, wealth and being married were all inversely related to OSCC. The strongest inverse association was found with education. Compared with no education, the adjusted odds ratios (95% confidence intervals) for primary education and high school or beyond were 0.52 (0.27-0.98) and 0.20 (0.06-0.65), respectively.Conclusions: The strong association of SES with OSCC after adjustment for known risk factors implies the presence of yet unidentified risk factors that are correlated with our SES measures; identification of these factors could be the target of future studies. Our results also emphasize the importance of using multiple SES measures in epidemiological studies. [ABSTRACT FROM AUTHOR]

Our objectives were to investigate patterns of food and nutrient consumption in Golestan province, a high-incidence area for esophageal cancer (EC) in northern Iran. Twelve 24-h dietary recalls were administered during a 1-yr period to 131 healthy participants in a pilot cohort study. We compare here nutrient intake in Golestan with recommended daily allowances (RDAs) and lowest threshold intakes (LTIs). We also compare the intake of 27 food groups and nutrients among several population subgroups using mean values from the 12 recalls. Rural women had a very low level of vitamin intake, which was even lower than LTIs (P < 0.01). Daily intake of vitamins A and C was lower than LTI in 67% and 73% of rural women, respectively. Among rural men, the vitamin intakes were not significantly different from LTIs. Among urban women, the vitamin intakes were significantly lower than RDAs but were significantly higher than LTIs. Among urban men, the intakes were not significantly different from RDAs. Compared to urban dwellers, intake of most food groups and nutrients, including vitamins, was significantly lower among rural dwellers. In terms of vitamin intake, no significant difference was observed between Turkmen and non-Turkmen ethnics. The severe deficiency in vitamin intake among women and rural dwellers and marked differences in nutrient intake between rural and urban dwellers may contribute to the observed epidemiological pattern of EC in Golestan, with high incidence rates among women and people with low socioeconomic status and the highest incidence rate among rural women. [ABSTRACT FROM AUTHOR]

The article discusses a study in Iran by Farhad Islami and colleagues that investigated the relationship between oesophageal squamous cell carcinoma and drinking hot tea. The study was a population based case-controlled study in Golestan province in northern Iran. The results of the study revealed an association between tea temperature and the risk of oesophageal cancer. Drinking hot tea or very hot tea increased the risk for cancer of the oesophagus. The authors also explore other contributing risk factors for oesophageal cancer and the strengths and limitations of the study.

One etiologic factor for high incidence of esophageal squamous cell carcinoma (ESCC) in Golestan (Northeastern Iran) might be exposure to polycyclic aromatic hydrocarbons. We examined whether food and water are major sources of benzo(a)pyrene (BaP) exposure in this population. We used a dietary questionnaire to assess the daily intake of staple food (rice and bread) and water in 3 groups: 40 ESCC Golestan cases, 40 healthy subjects from the same area, and 40 healthy subjects from a low-risk area in Southern Iran. We measured, by high-performance liquid chromatography combined with fluorescence detection, the BaP concentration of bread, rice, and water in samples obtained from these 3 groups and calculated the daily intake of BaP. Mean BaP concentration of staple foods and water was similar and within standard levels in both areas, but the daily intake of BaP was higher in controls from the high-risk area than in controls from the low-risk area (91.4 vs. 70.6 ng/day, P < 0.01). In the multivariate regression analysis, having ESCC had no independent effect on BaP, whereas residence in the low-risk area was associated with a significant decrease in total BaP intake. Polycyclic aromatic hydrocarbons might, along with other risk factors, contribute to the high risk of ESCC in Golestan. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests overall diet quality, as assessed by dietary scores, may play a role in the development of upper gastrointestinal (UGI) cancers. However, the existing dietary scores are derived from high-income countries with different dietary habits than regions with the highest burden of UGI cancers, where limited data is available. This study aimed to investigate the association between overall diet quality and risk of esophageal and stomach cancers in a high-risk region for UGI cancers. Methods: We recruited 50 045 individuals aged 40-75 between 2004-2008 from northeastern Iran and followed them annually through July 2020. Data on demographics, diet, and various exposures were collected using validated questionnaires. Diet quality was assessed by calculating the Healthy Eating Index (HEI), Alternative Healthy Eating Index (AHEI), Alternative Mediterranean Diet (AMED), Dietary Approaches to Stop Hypertension (DASH), and World Cancer Research Fund--American Institute for Cancer Research (WCRF-AICR) scores. Results: During an average 12 years of follow-up, 359 participants developed esophageal cancer and 358 developed stomach cancer. After adjustments, each standard deviation increase in baseline dietary scores was associated with up to 12% reduction in esophageal cancer risk and up to 17% reduction in stomach cancer risk. Esophageal cancer showed stronger inverse associations with adherence to AMED (HRQ4-vs-Q1 = 0.69 (0.49-0.98), P-trend = 0.038). Stomach cancer showed stronger inverse correlation with WCRF-AICR (HRQ4-vs-Q1 = 0.58 (0.41-0.83), P-trend = 0.004), and DASH (HRC4-vs-C1 = 0.72 (0.54-0.96), P-trend = 0.041). These associations were comparable across different population subgroups. We did not observe significant associations between HEI and AHEI scores and UGI cancers in this population. Conclusion: Despite the differences in consuming individual food groups, adherence to the available dietary recommendations (derived from high-income countries) was associated with lower risk for subsequent esophageal and gastric cancers in this high-risk population. Educating the public to have a healthy eating pattern might be an effective strategy towards prevention of UGI cancers in high-risk regions. [ABSTRACT FROM AUTHOR]

Introduction: Dietary protein comes from foods with greatly different compositions that may not relate equally with mortality risk. Few cohort studies from non-Western countries have examined the association between various dietary protein sources and cause-specific mortality. Therefore, the associations between dietary protein sources and all-cause, cardiovascular disease, and cancer mortality were evaluated in the Golestan Cohort Study in Iran.Methods: Among 42,403 men and women who completed a dietary questionnaire at baseline, 3,291 deaths were documented during 11 years of follow up (2004-2015). Cox proportional hazards models estimated age-adjusted and multivariate-adjusted hazard ratios (HRs) and 95% CIs for all-cause and disease-specific mortality in relation to dietary protein sources. Data were analyzed from 2015 to 2016.Results: Comparing the highest versus the lowest quartile, egg consumption was associated with lower all-cause mortality risk (HR=0.88, 95% CI=0.79, 0.97, ptrend=0.03). In multivariate analysis, the highest versus the lowest quartile of fish consumption was associated with reduced risk of total cancer (HR=0.79, 95% CI=0.64, 0.98, ptrend=0.03) and gastrointestinal cancer (HR=0.75, 95% CI=0.56, 1.00, ptrend=0.02) mortality. The highest versus the lowest quintile of legume consumption was associated with reduced total cancer (HR=0.72, 95% CI=0.58, 0.89, ptrend=0.004), gastrointestinal cancer (HR=0.76, 95% CI=0.58, 1.01, ptrend=0.05), and other cancer (HR=0.66, 95% CI=0.47, 0.93, ptrend=0.04) mortality. Significant associations between total red meat and poultry intake and all-cause, cardiovascular disease, or cancer mortality rate were not observed among all participants.Conclusions: These findings support an association of higher fish and legume consumption with lower cancer mortality, and higher egg consumption with lower all-cause mortality. [ABSTRACT FROM AUTHOR]

Background: The Gastro-Esophageal Malignancies in Northern Iran (GEMINI) research project is an example of recent progress in health research in Iran. The original aim of this project was to identify etiologic factors and prevention measures for upper gastrointestinal cancers in Northern provinces of Iran, but its achievements have gone much beyond this initial goal. Methods: GEMINI consists of several projects including cancer registries, pilot studies, case-control studies, and the Golestan Cohort Study. GEMINI has been conducted through extensive collaborations between the Digestive Disease Research Center of Tehran University of Medical Sciences with other domestic and international health organizations. The achievements of GEMINI include producing new knowledge, introducing new research methods, developing and expanding health research and health care infrastructures, investing in , human resources, and increasing the awareness and knowledge of policy makers and officials at all levels about the importance of chronic diseases in Iran's health priorities. Conclusions: The success of GEMINI reveals the feasibility of large-scale health research studies in developing countries and serves as , a successful model not only for health research in Iran, but also for similar research studies in other developing nations. [ABSTRACT FROM AUTHOR]

Abstract: Golestan Province, located in the south-east littoral of the Caspian Sea in northern Iran, has one of the highest rates of oesophageal cancer (OC) in the world. We review the epidemiologic studies that have investigated the epidemiologic patterns and causes of OC in this area and provide some suggestions for further studies. Oesophageal squamous cell carcinoma (OSCC) constitutes over 90% of all OC cases in Golestan. In retrospective studies, cigarettes and hookah smoking, nass use (a chewing tobacco product), opium consumption, hot tea drinking, poor oral health, low intake of fresh fruit and vegetables, and low socioeconomic status have been associated with higher risk of OSCC in Golestan. However, the association of tobacco with OSCC in this area is not as strong as that seen in Western countries. Alcohol is consumed by a very small percentage of the population and is not a risk factor for OSCC in this area. Other factors, such as polycyclic aromatic hydrocarbons, N-nitroso compounds, drinking water contaminants, infections, food contamination with mycotoxins, and genetic factors merit further investigation as risk factors for OSCC in Golestan. An ongoing cohort study in this area is an important resource for studying some of these factors and also for confirming the previously found associations. [Copyright &y& Elsevier]

Background: 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., (©2024 The Authors; Published by the American Association for Cancer Research.)

High-fat diets have been associated with colorectal cancer (CRC) risk, and the role of polyunsaturated fatty acids (PUFAs) has been reported to vary based on the length of PUFAs. We explored the association between dietary omega-6 and omega-3 PUFAs intake and CRC. We analyzed 865 CRC patients and 3206 controls from a case-control study of Iran (IROPICAN study). We used multivariate logistic regression models to calculate the odds ratios (OR) and 95% confidence intervals (CI) for the association between PUFAs intake and CRC risk. Our results showed that gamma-linolenic acid (18:3 n-6, GLA), arachidonic acid (20:4n-6, ARA), a-linolenic acid (Cis-18:3n-3, ALA), eicosapentaenoic acid (20:5n-3, EPA), docosahexaenoic acid (22:6n-3, DHA) consumption was not associated with the risk of CRC. However, the OR of linoleic acid (18: 2n-6, LA) intake was 1.47 (95% CI 1.01-2.14, p = 0.04) for proximal colon and that of docosapentaenoic acid (22:5n-3, DPA) intake was 1.33 (95% CI 1.05-1.69, p = 0.01) for rectum. This study indicates a high level of LA is associated with an increased risk of proximal colon cancer, and DPA intake was positively associated with rectum cancer risk. Furthermore, our study noted a high intake of n-6 (from vegetable oils) compared to n-3 PUFAs (from fish and seafood) in this population. Public awareness and government support is needed to increase fish and seafood production and consumption in Iran., (© 2024 AOCS.)

Controversy exists regarding the association of dietary advanced glycation end products (dAGEs) with the risk of disease outcomes and mortality. We aimed to examine, prospectively, the association between dAGEs intake and the risk of overall and cause-specific mortality in the Golestan Cohort Study. The cohort was conducted between 2004 and 2008 in Golestan Province (Iran) recruiting 50,045 participants aged 40-75 years. Assessment of dietary intake over the last year was performed at baseline using a 116-item food frequency questionnaire. The dAGEs values for each individual were calculated based on published databases of AGE values of various food items. The main outcome was overall mortality at the time of follow-up (13.5 years). Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cause-specific mortality were estimated according to the dAGEs quintiles. During 656, 532 person-years of follow-up, 5406 deaths in men and 4722 deaths in women were reported. Participants at the highest quintile of dAGE had a lower risk of overall mortality (HR: 0.89, 95% CI: 0.84, 0.95), CVD mortality (HR: 0.89, 95% CI: 0.84, 0.95), and death from other causes (HR: 0.89, 95% CI: 0.84, 0.95) compared to those in the first quintile after adjusting for confounders. We found no association of dAGEs with risk of mortality from cancer (all), respiratory and infectious diseases, and injuries. Our findings do not confirm a positive association between dAGEs and the risk of mortality in Iranian adults. There is still no agreement among studies investigating dAGEs and their health-related aspects. So, further high-quality studies are required to clarify this association.

Opium use was recently classified as a human carcinogen for lung cancer by the International Agency for Research on Cancer. We conducted a large, multicenter case-control study evaluating the association between opium use and the risk of lung cancer. We recruited 627 cases and 3477 controls from May 2017 to July 2020. We used unconditional logistic regression analyses to estimate the odds ratios (OR) and 95% confidence intervals (CI) and measured the association between opium use and the risk of lung cancer. The ORs were adjusted for the residential place, age, gender, socioeconomic status, cigarettes, and water pipe smoking. We found a 3.6-fold risk of lung cancer for regular opium users compared to never users (95% CI: 2.9, 4.6). There was a strong dose-response association between a cumulative count of opium use and lung cancer risk. The OR for regular opium use was higher for small cell carcinoma than in other histology (8.3, 95% CI: 4.8, 14.4). The OR of developing lung cancer among opium users was higher in females (7.4, 95% CI: 3.8, 14.5) than in males (3.3, 95% CI: 2.6, 4.2). The OR for users of both opium and tobacco was 13.4 (95% CI: 10.2, 17.7) compared to nonusers of anything. The risk of developing lung cancer is higher in regular opium users, and these results strengthen the conclusions on the carcinogenicity of opium. The association is stronger for small cell carcinoma cases than in other histology., (© 2022 UICC.)

Background: Globally, lung cancer is the most frequent occupational cancer, but the risk associated with the occupations or occupational environment in Iran is not clear. We aimed to assess occupations with the risk of lung cancer., Methods: We used the IROPICAN nationwide case-control study data including 658 incident lung cancer cases and 3477 controls. We assessed the risk of lung cancer in relation to ever working in major groups of International Standard Classification of Occupations, high-risk occupations for lung cancer and duration of employment and lung cancer subtype among construction workers and farmers while controlling for cigarette smoking and opium consumption. We used unconditional regression logistic models to estimate ORs for the association between increased lung cancer risk and occupations., Results: We observed elevated ORs for lung cancer in male construction workers (OR=1.4; 95% CI: 1.0 to 1.8), petroleum industry workers (OR=3.2; 95% CI: 1.1 to 9.8), female farmers (OR=2.6; 95% CI: 1.3 to 5.3) and female bakers (OR=5.5; 95% CI: 1.0 to 29.8). A positive trend by the duration of employment was observed for male construction workers (p< 0.001). Increased risk of squamous cell carcinoma was observed in male construction workers (OR=1.9; 95% CI: 1.2 to 3.0) and female farmers (OR=4.3; 95% CI: 1.1 to 17.2), who also experienced an increased risk of adenocarcinoma (OR=3.8; 95% CI: 1.4 to 9.9)., Discussion: Although we observed associations between some occupations and lung cancer consistent with the literature, further studies with larger samples focusing on exposures are needed to better understand the occupational lung cancer burden in Iran., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is evidence of an inverse association between yoghurt intake and risk of colorectal cancer (CRC). We aimed at investigating the association between the intake of yoghurt and other dairy foods consumed in Iran and CRC risk., Methods: Our analysis included 4070 subjects within the IROPICAN (Iran Study of Opium and Cancer) study. Detailed information was collected by the use of validated questionnaires. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between the intake of total dairy products, and, separately, of yoghurt, milk, cheese, kashk, dough, cream, ice cream, and other milk products, and CRC using unconditional logistic regression analyses. The intake was categorized in tertiles., Results: Overall, we analyzed 865 cases and 3205 controls. Total dairy products intake was not associated with CRC. The OR for one tertile increase (OR&#95;T) in yoghurt intake was 0.97 (95% CI 0.87-1.08) for CRC and 0.66 (95% CI 0.52-0.84) for proximal colon cancer. Cream intake was associated with CRC (OR&#95;T3 = 1.33, 95% CI 1.08-1.64), colon (OR&#95;T3 = 1.37, 95% CI 1.03-1.81), and proximal cancer (OR&#95;T3 = 1.29, 95% CI 1.04-1.61). The OR of distal colon cancer for ice cream intake was 0.59 (95% CI 0.43-0.82). Other dairy products were not associated with CRC risk.

Background: Bladder cancer (BC) is the 10th most common type of cancer worldwide and the fourth most common type of cancer in Iran. Opium use is considered as one of the risk factors for BC. We aim to assess the association between various parameters of opium use, which in Iran is mainly ingested or smoked in various forms, and the risk of BC., Method: In this multi-centre case-referent study in Iran, 717 BC cases and 3477 referents were recruited to the study from May 2017 until July 2020. Detailed histories of opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure adjusted odds ratio (OR) and 95% confidence intervals (CI). The ORs were adjusted for age, gender, place of residence and pack-years of cigarette smoking., Results: Regular opium consumption was associated with an increased risk of BC (OR 3.5, 95% CI: 2.8, 4.3) compared with subjects who never used opium. Compared with continuous users, the risk decreased to one-third for those who stopped opium more than 10 years ago. The adjusted OR for those who used both crude opium (teriak) and opium juice was 7.4 (95% CI: 4.1, 13.3). There was a joint effect of opium and tobacco (OR for users of both opium and tobacco 7.7, 95% CI: 6.0, 9.7)., Conclusions: Regular opium use is associated with an approximately 4-fold risk for BC. The OR decreases along with the increasing time since stopping opium use., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Introduction: Nonalcoholic fatty liver disease (NAFLD), as the most common liver disease in the world, can range from simple steatosis to steatohepatitis. We evaluated the association between meat consumption and risk of NAFLD in the Golestan Cohort Study (GCS)., Methods: The GCS enrolled 50,045 participants, aged 40-75 years in Iran. Dietary information was collected using a 116-item semiquantitative food frequency questionnaire at baseline (2004-2008). A random sample of 1,612 cohort members participated in a liver-focused study in 2011. NAFLD was ascertained through ultrasound. Total red meat consumption and total white meat consumption were categorized into quartiles based on the GCS population, with the first quartile as the referent group. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: The median intake of total red meat was 17 and total white meat was 53 g/d. During follow-up, 505 individuals (37.7%) were diagnosed with NAFLD, and 124 of them (9.2%) had elevated alanine transaminase. High total red meat consumption (ORQ4 vs Q1 = 1.59, 95% CI = 1.06-2.38, P trend = 0.03) and organ meat consumption (ORQ4 vs Q1 = 1.70, 95% CI = 1.19-2.44, P trend = 0.003) were associated with NAFLD. Total white meat, chicken, or fish consumption did not show significant associations with NAFLD., Discussion: In this population with low consumption of red meat, individuals in the highest group of red meat intake were at increased odds of NAFLD. Furthermore, this is the first study to show an association between organ meat consumption and NAFLD (see Visual Abstract, http://links.lww.com/AJG/B944)., (Copyright © 2021 by The American College of Gastroenterology.)

Tooth loss and periodontal disease have been associated with several cancers, and poor oral health may be an important risk factor for upper gastrointestinal (UGI, i.e., esophageal and gastric) cancers. We assessed the relationship between oral health and UGI cancers using a large prospective study of over 50,000 adults living in Golestan Province, Iran, a high-incidence area for these cancers. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for the association between three different measures of oral health [frequency of tooth brushing; number of missing teeth; and the sum of decayed, missing, and filled teeth (DMFT)] and UGI cancers. During a median follow-up duration of 13 years, there were 794 incident UGI cancers (396 esophageal and 398 gastric cancers). Daily tooth brushing was associated with a decreased risk of developing both esophageal (HR = 0.670; 95% CI: 0.486-0.924) and gastric (HR = 0.741; 95% CI: 0.544-1.01) cancers (combined UGI cancer HR = 0.697; 95% CI: 0.558-0.871) compared with never brushing. Tooth loss in excess of the loess smoothed, age- and sex-specific median number of teeth lost was significantly associated with esophageal (HR = 1.64; 95% CI: 1.08-2.47) and gastric cancers (HR = 1.58; 95% CI: 1.05-2.38). There were some adverse associations between DMFT and UGI cancers but most were not statistically significant. These results suggest increased risk of developing UGI cancers among individuals with poor oral health, and those who do not perform regular oral hygiene. PREVENTION RELEVANCE: Poor oral health is associated with the risk of upper gastrointestinal cancers, and oral hygiene practices may help prevent these cancers., (©2021 American Association for Cancer Research.)

Aims: Tens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of long-term opiate use with cardiovascular mortality and whether this association is independent of the known risk factors., Methods and Results: In the population-based Golestan Cohort Study-50 045 Iranian participants, 40-75 years, 58% women-we used Cox regression to estimate hazard ratios and 95% confidence intervals (HRs, 95% CIs) for the association of opiate use (at least once a week for a period of 6 months) with cardiovascular mortality, adjusting for potential confounders-i.e. age, sex, education, wealth, residential place, marital status, ethnicity, and tobacco and alcohol use. To show independent association, the models were further adjusted for hypertension, diabetes, waist and hip circumferences, physical activity, fruit/vegetable intake, aspirin and statin use, and history of cardiovascular diseases and cancers. In total, 8487 participants (72.2% men) were opiate users for a median (IQR) of 10 (4-20) years. During 548 940 person-years-median of 11.3 years, >99% success follow-up-3079 cardiovascular deaths occurred, with substantially higher rates in opiate users than non-users (1005 vs. 478 deaths/100 000 person-years). Opiate use was associated with increased cardiovascular mortality, with adjusted HR (95% CI) of 1.63 (1.49-1.79). Overall 10.9% of cardiovascular deaths were attributable to opiate use. The association was independent of the traditional cardiovascular risk factors., Conclusion: Long-term opiate use was associated with an increased cardiovascular mortality independent of the traditional risk factors. Further research, particularly on mechanisms of action, is recommended., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

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 and Objective: Overweight and obesity are thought to be associated with increased risk of chronic disease in the Middle East. The present study aimed to determine the association between dietary habits and the incidence of overweight and obesity in urban adult population in the central part of Iran after a 10-year follow-up., Methods: This cohort study was initiated with 2000 participation aged 20-74 years from Yazd city in Iran based on Yazd Healthy Heart Project (YHHP). The participants without overweight and obesity at the baseline of the study were followed up to 10 years. Demographic data, anthropometric measurements, behavioral and metabolic risk factors of cardiovascular diseases and dietary habits were assessed at baseline and phase II., Results: After a 10-year follow up, 516 non-overweight and 1068 non-obese participants were included for the final analysis. Once adjustments were made for all potential confounders including age, sex, smoking, economic status, physical activity and education, it was identified that lack of weight control increased the risk of obesity (hazard ratio; 95% CI) in total population (1.9; 1.06, 3.4), as well as the risk of overweight (2.39; 1.07, 5.27) and obesity (2.65; 1.13, 6.25) in men. Moreover, consumption of mayonnaise increased the 10-year risk of overweight in women (6.09; 1.2, 30.99)., Conclusions: As revealed by the present study, unhealthy dietary habits can increase the incidence of overweight and obesity in central part of Iran. Therefore, changing the lifestyle appears to be urgent in reducing the risk of overweight and obesity., Competing Interests: Declaration of competing interest On behalf of all the authors, the corresponding author states that there is no conflict of interest., (Copyright © 2020 Diabetes India. All rights reserved.)