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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 12years. 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.

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 10.6years 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.

Background: Nut consumption has been inversely associated with gastric cancer incidence in US-based studies, but not with oesophageal cancer. However, there is aetiologic heterogeneity, among oesophageal squamous cell carcinoma (ESCC) cases in low-risk vs. high-risk populations. The objective of this study was to evaluate the association between nut consumption and risk of ESCC in a high-risk population. Methods: The Golestan Cohort Study enroled 50,045 participants in Northeastern Iran, between 2004 and 2008. Intake of peanuts, walnuts and mixed nuts (including seeds) were assessed using a validated food frequency questionnaire at baseline. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals for subsequent ESCC adjusted for potential confounders. Non-consumers of nuts were used as the reference category and the consumers were categorised into tertiles. Results: We accrued 280 incident ESCC cases during 337,983 person-years of follow up. Individuals in the highest tertiles of total nut consumption, and mixed nut consumption were significantly associated with lower risk of developing ESCC compared to non-consumers (HR = 0.60, 95% CI = 0.39-0.93, p-trend = 0.02, and HR = 0.52, 95% CI = 0.32-0.84, p trend = 0.002, respectively). Conclusions: We found a statistically significant inverse association between total nut consumption and the risk of ESCC in this high-risk population.

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. © 2017 The Author.

Cooking practices and water sources have been associated with an increased risk of cancer, mainly through exposure to carcinogens such as heterocyclic amines, polycyclic aromatic hydrocarbons, and nitrates. Using data from the Golestan case-control study, carried out between 2003 and 2007 in a high-risk region for esophageal squamous cell carcinoma (ESCC), we sought to investigate the association between food preparation and drinking water sources and ESCC. Information on food preparation methods, sources of drinking water, and dietary habits was gathered from 300 cases and 571 controls matched individually for age, sex, and neighborhood using a structured questionnaire and a semiquantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounders and other known risk factors including socioeconomic status and smoking. More than 95% of the participants reported eating meat, mostly red meat. Red meat consumption above the 75th percentile increased the odds of ESCC by 2.82-fold (95% CI: 1.21-6.57). Fish intake was associated with a significant 68% decrease in ESCC odds (26%, 86%). Among meat eaters, ORs (95% CI) for frying meat (red or white) and fish were 3.34 (1.32-8.45) and 2.62 (1.24-5.5). Drinking unpiped water increased ESCC odds by 4.25 times (2.23-8.11). The OR for each 10-year increase in the duration of drinking unpiped water was 1.47 (1.22-1.78). Our results suggest roles for red meat intake, drinking water source, and food preparation methods in ESCC, even after adjusting for a large number of potential confounders. © 2016 Wolters Kluwer Health, Inc. All rights reserved.

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. © 2016 American Journal of Preventive Medicine

Current evidence is inconsistent about the association between dietary protein intake and risk of pancreatic cancer (PC). The aim of this study was to evaluate the association between total intake of major dietary protein sources and risk of PC in a large prospective study in Golestan Cohort Study (GCS).We examined the association of total intake of major dietary protein sources with risk of PC in the 50,045 participants (20,855 men and 28,255 women) of the GCS in northeastern Iran. Participants were aged 40 and older at baseline and actively followed from 2004 to the present time. Dietary data were collected using a validated semi-quantitative food-frequency questionnaire that was administered at baseline. Cox proportional hazards models were used to estimate Multivariable hazard ratios with 95% confidence intervals (CI).During 383,630 person-years of follow-up, 54 cases of pancreatic cancer were ascertained. There was only a statistically significant inverse association between risk of PC for the second versus lowest tertile of plant based protein intake in the first and multivariable models (HR = .27, 95% CI = .12-.64, HR = .28, 95% CI = .12 -.65 respectively); however, this association was not significant anymore when comparing the highest tertile with the lowest one, in the first and multivariable models (HR = .49, 95% CI = .19-1.24, HR = .52, 95% CI = .20-1.34 respectively).In this large prospective cohort, we did not observe any clear and consistent evidence for an association between main dietary.

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Background: Cardiovascular disease and obesity are now becoming leading causes of morbidity and mortality in low- and middle-income countries.Objectives: We investigated the relationship between prevalent heart disease (HD) and current anthropometric indices and body size perception over time from adolescence to adulthood in Iran.Methods: We present a cross-sectional analysis of baseline data from a prospective study of adults in Golestan Province, Iran. Demographics, cardiac history, and current anthropometric indices—body mass index, waist circumference, and waist to hip ratio—were recorded. Body size perception for ages 15 years, 30 years, and at the time of interview was assessed via pictograms. Associations of these factors and temporal change in perceived body size with HD were evaluated using multivariable logistic regression models.Results: Complete data were available for 50,044 participants; 6.1% of which reported having HD. Higher body mass index, waist circumference, and waist to hip ratio were associated with HD (p < 0.001). Men had a U-shaped relationship between HD and body size perception at younger ages. For change in body size perception, men and women demonstrated a U-shaped relationship with prevalent HD from adolescence to early adulthood, but a J-shaped pattern from early to late adulthood.Conclusions: HD was associated with anthropometric indices and change in body size perception over time for men and women in Iran. Due to the increasing prevalence of overweight and obesity in low- and middleincome countries, interventions focused on decreasing the cumulative burden of risk factors throughout the life course may be an important component of cardiovascular risk reduction.HighlightsWe present a cross-sectional analysis of baseline data from a prospective study of adults in Golestan Province, Iran, to investigate the relationship between prevalent heart disease (HD) and current anthropometric indices and body size perception over time from adolescence to adulthood in Iran.Body size perception for age 15 years, age 30 years, and at the time of interview was assessed via pictograms.For men and women, higher body mass index, waist circumference, and waist-hip ratio were associated with HD.Men had a U-shaped relationship between HD and body size perception at younger ages.For change in body size perception, men and women demonstrated a U-shaped relationship with prevalent HD from adolescence to early adulthood, but a J-shaped pattern from early to late adulthood.

Background: Both high and low body mass index (BMI) are associated with heart disease (HD). However, data are relatively lacking regarding the relationship between life-course trends in BMI and HD in low- and middle-income countries (LMICs). Objective: To investigate the relationship between prevalent HD and anthropomorphic indices such as BMI, waist circumference (WC) and waist to hip ratio (WHR), as well as body size perception from adolescence to adulthood. Methods: Baseline data from the Golestan Cohort Study, a prospective population-based study in Iran, were used in this cross-sectional analysis. Current anthropometric indices were measured and body size perception using standard pictograms was assessed for age 15, age 30, and at the time of interview. We used logistic regression to evaluate associations of prevalent HD with anthropometric indices. Statistical analyses were performed using STATA version 11. Results: Complete data were available for 50,044 participants (age 40-75 years), of whom 6.1% reported a history of HD. For men and women, current BMI, WC, and WHR were associated with prevalent HD (p Conclusion: Prevalent HD was associated with current anthropometric indices and temporal changes in body size perception for men and women. Public health interventions focused on the cumulative lifetime burden of risk factors such as obesity on cardiovascular morbidity and mortality are essential, particularly in LMICs.

Polycyclic aromatic hydrocarbons (PAHs) likely play a role in many cancers even in never-smokers. We tried to find a model to explain the relationship between variation in PAH-related DNA adduct levels among people with similar exposures, multiple genetic polymorphisms in genes related to metabolic and repair pathways, and nucleotide excision repair (NER) capacity. In 111 randomly selected female never-smokers from the Golestan Cohort Study in Iran, we evaluated 21 SNPs in 14 genes related to xenobiotic metabolism and 12 SNPs in eight DNA repair genes. NER capacity was evaluated by a modified comet assay, and aromatic DNA adduct levels were measured in blood by32P-postlabeling. Multivariable regression models were compared by Akaike's information criterion (AIC). Aromatic DNA adduct levels ranged between 1.7 and 18.6 per 10(8) nucleotides (mean: 5.8 ± 3.1). DNA adduct level was significantly lower in homozygotes for NAT2 slow alleles and ERCC5 non-risk-allele genotype, and was higher in the MPO homozygote risk-allele genotype. The sum of risk alleles in these genes significantly correlated with the log-adduct level (r = 0.4, p < 0.001). Compared with the environmental model, adding Phase I SNPs and NER capacity provided the best fit, and could explain 17% more of the variation in adduct levels. NER capacity was affected by polymorphisms in the MTHFR and ERCC1 genes. Female non-smokers in this population had PAH-related DNA adduct levels three to four times higher than smokers and occupationally-exposed groups in previous studies, with large inter-individual variation which could best be explained by a combination of Phase I genes and NER capacity. Grant sponsor: Environmental Cancer Risk, Nutrition and Individual Susceptibility (ECNIS), a network of excellence operating within the European Union 6th Framework Program [Priority 5: ‘‘Food Quality and Safety’’]; Grant number: 513943

Studies have suggested a possible role of polycyclic aromatic hydrocarbons (PAHs) in the etiology of esophageal cancer in Golestan Province, Iran, where incidence of this cancer is very high. In order to investigate the patterns of non-smoking related exposure to PAHs in Golestan, we conducted a cross-sectional study collecting questionnaire data, genotyping polymorphisms related to PAH metabolism, and measuring levels of 1-hydroxypyrene glucuronide (1-OHPG), a PAH metabolite, in urine samples collected in two seasons from the same group of 111 randomly selected never-smoking women. Beta-coefficients for correlations between 1-OHPG as dependent variable and other variables were calculated using linear regression models. The creatinine-adjusted 1-OHPG levels in both winter and summer samples were approximately 110 μmol/molCr (P for seasonal difference = 0.40). In winter, red meat intake (β = 0.208; P = 0.03), processed meat intake (β = 0.218; P = 0.02), and GSTT1-02 polymorphism ("null" genotype: β = 0.228; P = 0.02) showed associations with 1-OHPG levels, while CYP1B1-07 polymorphism (GG versus AA + GA genotypes: β = -0.256; P = 0.008) showed an inverse association. In summer, making bread at home (> weekly versus never: β = 0.203; P = 0.04), second-hand smoke (exposure to ≥3 cigarettes versus no exposure: β = 0.254; P = 0.01), and GSTM1-02 "null" genotype (β = 0.198; P = 0.04) showed associations with 1-OHPG levels, but GSTP1-02 polymorphism (CT + TT versus CC: β = -0.218; P = 0.03) showed an inverse association. This study confirms high exposure of the general population in Golestan to PAHs and suggests that certain foods, cooking methods, and genetic polymorphisms increase exposure to PAHs. Data and sample collection was supported by Digestive Disease Research Center of Tehran University of Medical Sciences and International Agency for Research on Cancer. Laboratory assessments were funded by ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program [Priority 5: “Food Quality and Safety” (Contract No. 513943)].

Dietary factors seem to play a major role in esophageal carcinogenesis in Golestan Province, a high-incidence area for esophageal cancer in northern Iran. The current study was conducted to evaluate previous reports on severe deficiency of vitamin intake in Golestan.Using a food frequency questionnaire, food intake data were collected from 30,463 healthy participants in the Golestan Cohort Study. Intake of selected nutrients was compared with recommended daily allowance and lowest threshold intake values.Vitamin A intake in the majority of participants was lower than recommended values. The proportion of participants with intakes lower than lowest threshold intake was as follows: urban men, 20%; urban women, 31%; rural men, 48%; and rural women, 64%. The pattern of vitamin C deficiency was similar to that of vitamin A, however, vitamin C deficiency was less common. Daily intake of vitamin C lower than the LTI was as follows: urban men, 6%; urban women, 9%; rural men, 13%; and rural women, 19%. On the other hand, protein intake in the majority of the general population in Golestan was higher than recommended values.Severe deficiency in vitamin intake among women and rural dwellers may partly explain the high incidence of EC among inhabitants in rural areas and the male:female ratio that is approximately 1 in Golestan; while EC is much more common in men in many low-incidence areas.

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.

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. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

To investigate the incidence of oesophageal cancer (EC) in the Golestan province of North-East Iran, we invited 1349 rural and urban inhabitants of Golestan province aged 35-80 to undergo extensive lifestyle interviews and to provide biological samples. The interview was repeated on a subset of 130 participants to assess reliability of questionnaire and medical information. Temperature at which tea was consumed was measured on two occasions by 110 subjects. Samples of rice, wheat and sorghum were tested for fumonisin contamination. An active follow-up was carried out after 6 and 12 months. A total of 1057 subjects (610 women and 447 men) participated in this feasibility study (78.4% participation rate). Cigarette smoking, opium and alcohol use were reported by 163 (13.8%), 93 (8.8%) and 39 (3.7%) subjects, respectively. Tobacco smoking was correlated with urinary cotinine (? = 0.74). Most questionnaire data had ? > 0.7 in repeat measurements; tea temperature measurement was reliable (? = 0.71). No fumonisins were detected in the samples analysed. During the follow-up six subjects were lost (0.6%), two subjects developed EC (one dead, one alive); in all, 13 subjects died (with cause of death known for 11, 84.6%). Conducting a cohort study in Golestan is feasible with reliable information obtained for suspected risk factors; participants can be followed up for EC incidence and mortality. © 2005 Cancer Research UK.