Dental health and lung cancer risk in the Golestan Cohort Study.

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.

Sex and smoking differences in the association between gastroesophageal reflux and risk of esophageal squamous cell carcinoma in a high-incidence area: Golestan Cohort Study.

Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in-person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66-1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post-hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27-0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08-0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development.

Association Between Incident Type 2 Diabetes and Opium Use: Mediation by Body Mass and Adiposity.

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.

Polypill for prevention of cardiovascular diseases with focus on non-alcoholic steatohepatitis: the PolyIran-Liver trial.

AIMS: Individuals with non-alcoholic steatohepatitis or elevated liver enzymes have increased cardiovascular mortality but are often excluded from prevention trials. We investigated the effectiveness of fixed-dose combination therapy for the prevention of major cardiovascular events (MCVE) among individuals with and without presumed non-alcoholic steatohepatitis (pNASH). METHODS AND RESULTS: Two thousand four hundred participants over 50 were randomized into the intervention and control groups. Consent was obtained post-randomization. Consenting participants in the intervention group were given a pill containing aspirin, atorvastatin, hydrochlorothiazide, and valsartan (polypill). Participants were followed for 5 years. Presumed non-alcoholic steatohepatitis was diagnosed by ultrasonography and elevated liver enzymes. The primary outcome was MCVE. ClinicalTrials.gov: NCT01245608. Among the originally randomized population, 138 of 1249 in the intervention group (11.0%) and 137 of 1017 controls (13.5%) had MCVE during the 5-year follow-up [unadjusted risk ratio (RR) 0.83, 95% confidence interval (CI) 0.66-1.03]. Of the 1508 participants who consented to additional measurements and treatment, 63 of 787 (8.0%) intervention group participants and 86 of 721 (11.9%) controls had MCVE (adjusted RR 0.61, 95% CI 0.44-0.83). Although the adjusted relative risk of MCVE in participants with pNASH (0.35, 95% CI 0.17-0.74) was under half that for participants without pNASH (0.73, 95% CI 0.49-1.00), the difference did not reach statistical significance. There was no change in liver enzymes in participants taking polypill but among those with pNASH, there was a significant decrease after 60 months of follow-up (intragroup -12.0 IU/L, 95% CI -14.2 to -9.6). CONCLUSION: Among patients consenting to receive fixed-dose combination therapy, polypill is safe and effective for the prevention of MCVE, even among participants with fatty liver and increased liver enzymes.

Meat consumption and risk of esophageal and gastric cancer in the Golestan Cohort Study, Iran.

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.

An international report on bacterial communities in esophageal squamous cell carcinoma.

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients.

Incidence, early case fatality and determinants of stroke in Iran: Golestan Cohort Study.

OBJECTIVES: While few studies investigated the incidence of stroke in Iran, no Iranian cohort has estimated the standardized-incidence rate and early fatality of first-ever-stroke subtypes along with associated factors. METHODS: Golestan Cohort Study is a prospective study launched in northeastern Iran in 2004, including 50,045 individuals aged 40-75 at baseline. Age-standardized incidence rate of first-ever-stroke was calculated per 100,000 person-years, according to World Standard Population. The 28-day case fatality was calculated by dividing the number of fatal first-ever-stroke during the first 28 days by total events. Cox proportional hazard models were conducted to assess incidence and fatality risk factors. We used Population Attributable Fractions to estimate the incidence and early fatality proportions reduced by ideal risk factor control. RESULTS: 1,135 first-ever-strokes were observed during 8.6 (median) years follow-up. First-ever-stroke standardized incidence rate was estimated 185.2 (95% CI: 173.2-197.2) per 100,000 person-years. The 28-day case fatality was 44.1% (95% CI: 40.4-48.2). Hypertension and pre-stroke physical activity were the strongest risk factors associated with first-ever-stroke incidence (Hazard ratio: 2.83; 2.47-3.23) and 28-day case fatality (Hazard ratio: 0.59; 0.44-0.78), respectively. Remarkably, opium consumption was strongly associated with hemorrhagic stroke incidence (Hazard ratio: 1.52; 1.04-2.23) and ischemic stroke fatality (Hazard ratio: 1.44; 1.01-2.09). Overall, modifiable risk factors contributed to 83% and 61% of first-ever-stroke incidence and early fatality, respectively. CONCLUSION: Efficient risk factor control can considerably reduce stroke occurrence and fatality in our study. Establishing awareness campaigns and 24-hour stroke units seem necessary for improving the stroke management in this area.

Dietary quality using four dietary indices and lung cancer risk: the Golestan Cohort Study (GCS).

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.

A prospective study of tea drinking temperature and risk of esophageal squamous cell carcinoma.

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.

Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial.

BACKGROUND: A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease. METHODS: The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40-75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle-eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome-occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)-was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov, number NCT01271985. FINDINGS: Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study-3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5%) of 3421 participants in the polypill group were women, as were 1679 (49·1%) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5% (IQR 48·5-92·2). During follow-up, 301 (8·8%) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9%) of 3421 participants in the polypill group (adjusted hazard ratio [HR] 0·66, 95% CI 0·55-0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49-0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51-1·12; pinteraction=0·19). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0·43, 95% CI 0·33-0·55). The frequency of adverse events was similar between the two study groups. 21 intracranial haemorrhages were reported during the 5 years of follow-up-ten participants in the polypill group and 11 participants in the minimal care group. There were 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group. INTERPRETATION: Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs. FUNDING: Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou.

Individual and Combined Effects of Environmental Risk Factors for Esophageal Cancer Based on Results From the Golestan Cohort Study.

BACKGROUND & AIMS: Northeast Iran has one of the highest reported rates of esophageal squamous cell carcinoma (ESCC) worldwide. Decades of investigations in this region have identified some local habits and environmental exposures that increase risk. We analyzed data from the Golestan Cohort Study to determine the individual and combined effects of the major environmental risk factors of ESCC. METHODS: We performed a population-based cohort of 50,045 individuals, 40 to 75 years old, from urban and rural areas across Northeast Iran. Detailed data on demographics, diet, lifestyle, socioeconomic status, temperature of drinking beverages, and different exposures were collected using validated methods, questionnaires, and physical examinations, from 2004 through 2008. Participants were followed from the date of enrollment to the date of first diagnosis of esophageal cancer, date of death from other causes, or date of last follow-up, through December 31, 2017. Proportional hazards regression models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between different exposures and ESCC. RESULTS: During an average 10 years of follow-up, 317 participants developed ESCC. Opium smoking (HR 1.85; 95% CI 1.18-2.90), drinking hot tea (≥60°C) (HR 1.60; 95% CI 1.15-2.22), low intake of fruits (HR 1.48; 95% CI 1.07-2.05) and vegetables (HR 1.62; 95% CI 1.03-2.56), excessive tooth loss (HR 1.66; 95% CI 1.04-2.64), drinking unpiped water (HR 2.04; 95% CI 1.09-3.81), and exposure to indoor air pollution (HR 1.57; 95% CI 1.08-2.29) were significantly associated with increased risk of ESCC, in a dose-dependent manner. Combined exposure to these risk factors was associated with a stepwise increase in the risk of developing ESCC, reaching a more than 7-fold increase in risk in the highest category. Approximately 75% of the ESCC cases in this region can be attributed to a combination of the identified exposures. CONCLUSIONS: Analysis of data from the Golestan Cohort Study in Iran identified multiple risk factors for ESCC in this population. Our findings support the hypothesis that the high rates of ESCC are due to a combination of factors, including thermal injury (from hot tea), exposure to polycyclic aromatic hydrocarbons (from opium and indoor air pollution), and nutrient-deficient diets. We also associated ESCC risk with exposure to unpiped water and tooth loss.

The combination of sofosbuvir and daclatasvir is effective and safe in treating patients with hepatitis C and severe renal impairment.

BACKGROUND AND AIM: Many of the treatment regimens available for hepatitis C include sofosbuvir. Unfortunately, sofosbuvir has not been recommended for use in patients with severe renal impairment leaving these group of patients with very few options. Nevertheless, there are many reports in which these patients have been treated with sofosbuvir-containing regiments without important adverse events. This study aims at determining the safety and effectiveness of a sofosbuvir-based treatment in patients with severe renal impairment, including those on hemodialysis. METHOD: We enrolled subjects with hepatitis C and estimated glomerular filtration rate under ml/min/1.73m2 from 13 centers in Iran. Patients were treated for 12 weeks with a single daily pill containing 400-mg sofosbuvir and 60-mg daclatasvir. Patients with cirrhosis were treated for 24 weeks. Response to treatment was evaluated 12 weeks after end of treatment (sustained viral response [SVR]). ClinicalTrials.gov identifier: NCT03063879. RESULTS: A total of 103 patients were enrolled from 13 centers. Seventy-five patients were on hemodialysis. Thirty-nine had cirrhosis and eight were decompensated. Fifty-three were Genotype 1, and 27 Genotype 3. Twenty-seven patients had history of previous failed interferon-based treatment. Three patients died in which cause of death was not related to treatment. Six patients were lost to follow-up. The remaining 94 patients all achieved SVR. No adverse events leading to discontinuation of medicine was observed. CONCLUSIONS: The combination of sofosbuvir and daclatasvir is an effective and safe treatment for patients infected with all genotypes of hepatitis C who have severe renal impairment, including patients on hemodialysis.

Habitual dietary intake of flavonoids and all-cause and cause-specific mortality: Golestan cohort study.

BACKGROUND AND OBJECTIVES: Flavonoids are the most important group of polyphenols with well-known beneficial effects on health. However; the association of intake of total flavonoid or their subclasses with all-cause or cause-specific mortality is not fully understood. The present study aims to evaluate the association between intake of total flavonoid, flavonoid subclasses, and total and cause-specific mortality in a developing country. METHODS: A total number of 49,173 participants from the Golestan cohort study, who completed a validated food frequency questionnaire at recruitment, were followed from 2004 till 2018. Phenol-Explorer database was applied to estimate dietary intakes of total flavonoid and different flavonoid subclasses. Associations were examined using adjusted Cox proportional hazards models. RESULTS: During a mean follow-up of 10.63 years, 5104 deaths were reported. After adjusting for several potential confounders, the hazard ratios (HRs) of all-cause mortality for the highest versus the lowest quintile of dietary flavanones, flavones, isoflavonoids, and dihydrochalcones were 0.81 (95% confidence interval = 0.73-0.89), 0.83(0.76-0.92), 0.88(0.80-0.96) and 0.83(0.77-0.90), respectively. However, there was no association between total flavonoid intake or other flavonoid subclasses with all-cause mortality. In cause-specific mortality analyses, flavanones and flavones intakes were inversely associated with CVD mortality [HRs: 0.86(0.73-1.00) and 0.85(0.72-1.00)] and isoflavonoids and dihydrochalcones were the only flavonoid subclasses that showed a protective association against cancer mortality [HR: 0.82(0.68-0.98)]. CONCLUSION: The results of our study suggest that certain subclasses of flavonoids can reduce all-cause mortality and mortality rate from CVD and cancer.

The application of six dietary scores to a Middle Eastern population: a comparative analysis of mortality in a prospective study.

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.

Nut consumption and the risk of oesophageal squamous cell carcinoma in the Golestan Cohort Study.

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.

Dairy Food Intake and All-Cause, Cardiovascular Disease, and Cancer Mortality: The Golestan Cohort Study.

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.

Mortality from respiratory diseases associated with opium use: a population-based cohort study.

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.

White rice intake and incidence of type-2 diabetes: analysis of two prospective cohort studies from Iran.

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.

Chronic hepatitis B infection is not associated with increased risk of vascular mortality while having an association with metabolic syndrome.

This study aimed to assess the association of chronic hepatitis B (CHB) with vascular mortality and metabolic syndrome (MS) using data from a large population-based cohort study in Iran. A total of 12,781 participants (2249 treatment-naïve CHB and 10,532 without CHB) were studied. Logistic regression model was used to assess the association between MS and CHB with adjustment for age, ALT, PLT, alcohol intake, smoking, exercise, and socioeconomic status. MS was defined according to the ATPIII guidelines. Cox proportional hazards model was used to assess the hazard ratios for overall and vascular related mortality. There was a significant association between CHB infection and overall mortality (hazard ratio (95%CI) of 1.44 (1.16-1.79), P < 0.001) after adjusting for other confounders. However, we found no association between CHB infection and mortality from vascular events (hazard ratio (95%CI) of 1.31 (0.93-1.84), P = 0.124) even after subgroup analysis by ALT. Furthermore, increased risk of overall mortality in CHB infected individuals was not related to MS and vice versa (P for interaction = 0.06). We noted a significant direct association between CHB infection and MS in women (OR (95%CI); 1.23 (1.07-1.42), P < 0.004). However, CHB was inversely associated with MS in men (OR (95%CI), 0.85 (0.79-0.99). This gender dependent association was related to high BP levels in women. In this study no association between CHB infection and mortality from vascular events was found. Further longitudinal studies should be done to investigate the exact impact of HBV infection on metabolic parameters and vascular pathology.

Impact of body size and physical activity during adolescence and adult life on overall and cause-specific mortality in a large cohort study from Iran.

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.