Publications by authors named "Arash Etemadi"

109 Publications

Obesity and incident gastrointestinal cancers: overall body size or central obesity measures, which factor matters?

Eur J Cancer Prev 2021 May;30(3):267-274

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

BMI does not reflect the location or amount of body fat. We aimed to investigate the role of general and central obesity measures in the prediction of incident gastrointestinal cancers. In this analysis of the Golestan Cohort Study, we included 47 586 cancer-free individuals followed for 12.3 years (IQR: 10.5-13.2). We investigated the association of obesity measures including BMI, waist circumference and waist-to-hip ratio (WHR) at enrollment and the incidence of esophageal, gastric, colorectal and pancreatic cancers. Cox proportional hazard models were used to estimate the association between covariates and gastrointestinal cancer risk. We observed no significant associations between obesity measures and incidence of the above-mentioned gastrointestinal cancers in men. In women, BMI, waist circumference and WHR were associated with significant reductions in the risk of esophageal squamous cell carcinoma (ESCC): hazard ratio (HR): 0.67 [95% confidence interval (CI): 0.56-0.81], HR: 0.71 (95% CI: 0.60-0.84) and HR: 0.80 (95% CI: 0.68- 0.94), respectively. In addition, WHR was associated with significantly increased risks for colorectal cancer (HR: 1.39, 95% CI: 1.08-1.78) and gastric cancer (HR: 1.24, 95% CI: 1.01-1.51) in women. In this study, statistically significant associations between obesity measures and incident esophageal, gastric and colorectal cancers were seen in women.
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http://dx.doi.org/10.1097/CEJ.0000000000000657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015184PMC
May 2021

Red Meat Consumption and Risk of Nonalcoholic Fatty Liver Disease in a Population With Low Meat Consumption: The Golestan Cohort Study.

Am J Gastroenterol 2021 Mar 24. Epub 2021 Mar 24.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Departments of Biology, School of Art and Sciences, Utica College, Utica, New York, USA; Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Biology, School of Computer, Mathematical, and Natural Sciences, Morgan State University, Baltimore, Maryland, USA; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA; Departments of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Genetic Epidemiology Group, Section of Genetics, International Agency for Research on Cancer, the World Health Organization, Lyon, France; Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

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).
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http://dx.doi.org/10.14309/ajg.0000000000001229DOI Listing
March 2021

Concentrations of cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in US non-daily cigarette smokers.

Cancer Epidemiol Biomarkers Prev 2021 Mar 18. Epub 2021 Mar 18.

Department of Cancer Epidemiology and Genetics, National Cancer Institute.

Background: Accumulating evidence suggests that non-daily smokers have higher disease and mortality risks than never smokers. Yet, the accuracy of self-reported non-daily cigarette smoking is poorly understood.

Methods: We examined the concordance between self-reported non-daily smoking and serum cotinine in 18,835 adult participants (20 years or older) of the 2007-2014 National Health and Nutrition Examination Surveys, in comparison with daily smokers and non-smokers. We also analyzed concentrations of the urinary biomarker 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by smoking status.

Results: In the study sample, 77.8% (14,660) reported currently not smoking (non-smokers), 18.3% (3,446) smoked every day (daily smokers) and 3.9% (729) smoked on some days of the past month (non-daily smokers). Just 2.1% of non-smokers had cotinine concentrations in the active smoking range (>10 ng/mL), compared to 70.4% of non-daily and 98.8% of daily smokers. Non-daily smokers reported smoking a median of 24 cigarettes per month (interquartile range (IQR): 9-60) and had substantially higher concentrations of NNAL (Median: 72.5, IQR: 14.8-211.0 pg/mL) than non-smokers (Median: 0.4, IQR: 0.4-2.1 pg/mL), though lower than daily smokers (Median: 294.0, IQR: 148.0-542.0 pg/mL). Among non-daily smokers, concentrations of cotinine and NNAL were positively correlated with days and cigarettes smoked per month (P<0.001).

Conclusions: We observed excellent concordance between self-reported non-daily cigarette smoking and concentrations of serum cotinine.

Impact: These results provide evidence for the validity of self-reported non-daily smoking and indicate that non-daily smokers are exposed to substantial concentrations of carcinogenic nitrosamines regardless of the low number of cigarettes they smoke per month.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1601DOI Listing
March 2021

Oral Health and Risk of Upper Gastrointestinal Cancers in a Large Prospective Study from a High-risk Region: Golestan Cohort Study.

Cancer Prev Res (Phila) 2021 Mar 17. Epub 2021 Mar 17.

Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.

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.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0577DOI Listing
March 2021

Indoor wood combustion, carcinogenic exposure and esophageal cancer in southwest Kenya.

Environ Int 2021 Mar 6;152:106485. Epub 2021 Mar 6.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) is a risk factor for esophageal squamous cell carcinoma (ESCC) in high-incidence areas of China, Iran and Brazil, but PAH assessments have not been conducted in East Africa, another ESCC hot spot.

Objective: To evaluate demographic or lifestyle factors associated with the PAH biomarker concentrations in the study population, and whether PAH metabolite concentrations showed any associations with esophageal precancerous lesions.

Methods: We recruited a community-based sample of 289 asymptomatic adults from a rural area of Kenya and performed Lugol's chromoendoscopy to detect esophageal squamous dysplasia (ESD); participants completed a questionnaire and provided a spot urine specimen. We analyzed urine for seven hydroxylated metabolites of naphthalene, fluorene, phenanthrene, and pyrene at the U.S. National Center for Environmental Health, and compared creatinine-corrected PAH metabolite concentrations with questionnaire data and the presence of ESD.

Results: PAH metabolite concentrations among never tobacco users in these rural Kenya residents were 2.4-28.1 times higher than those reported from never tobacco users in Iran, Brazil and the USA. Female sex, cooking indoors, having no post-primary education, and age <50, but not tobacco use, were positively and significantly associated with PAH metabolite concentrations. Almost all participants used wood as cooking fuel. Nine participants had advanced ESD. Adjusted logistic regression showed a significant association between 2-hydroxynaphthalene (OR = 4.19, 95%CI: 1.01-17.47) and advanced ESD. All other PAH metabolites had positive but non-significant associations with advanced ESD.

Conclusions: Urinary PAH metabolite concentrations among never tobacco users are markedly higher in this group from Kenya than in other populations and are associated with indoor cooking with wood on open, unvented stoves. These metabolite concentrations were also associated with the presence of advanced esophageal dysplasia. Our findings underline the importance of assessing alternative cooking conditions to reduce PAH exposure in this population.
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http://dx.doi.org/10.1016/j.envint.2021.106485DOI Listing
March 2021

Long-term opiate use and risk of cardiovascular mortality: results from the Golestan Cohort Study.

Eur J Prev Cardiol 2021 Mar;28(1):98-106

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran 14117-13135, Iran.

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.
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http://dx.doi.org/10.1093/eurjpc/zwaa006DOI Listing
March 2021

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

Cancer Causes Control 2021 May 21;32(5):493-503. Epub 2021 Feb 21.

Stony Brook Cancer Center, New York, NY, USA.

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 p 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 p 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.
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http://dx.doi.org/10.1007/s10552-021-01400-wDOI Listing
May 2021

Metabolomics reveals biomarkers of opioid use disorder.

Transl Psychiatry 2021 Feb 4;11(1):103. Epub 2021 Feb 4.

Department of Nutrition, Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Opioid use disorder (OUD) is diagnosed using the qualitative criteria defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Diagnostic biomarkers for OUD do not currently exist. Our study focused on developing objective biological markers to differentiate chronic opiate users with OUD from chronic opiate users without OUD. Using biospecimens from the Golestan Cohort Study, we compared the metabolomics profiles of high opium users who were diagnosed as OUD positive with high opium users who were diagnosed as OUD negative. High opium use was defined as maximum weekly opium usage greater than or equal to the median usage (2.4 g per week), and OUD was defined as having 2 or more DSM-5 criteria in any 12-month period. Among the 218 high opium users in this study, 80 were diagnosed as OUD negative, while 138 were diagnosed as OUD positive. Seven hundred and twelve peaks differentiated high opium users diagnosed as OUD positive from high opium users diagnosed as OUD negative. Stepwise logistic regression modeling of subject characteristics data together with the 712 differentiating peaks revealed a signature that is 95% predictive of an OUD positive diagnosis, a significant (p < 0.0001) improvement over a 63% accurate prediction based on subject characteristic data for these samples. These results suggest that a metabolic profile can be used to predict an OUD positive diagnosis.
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http://dx.doi.org/10.1038/s41398-021-01228-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862627PMC
February 2021

Untargeted Metabolomics: Biochemical Perturbations in Golestan Cohort Study Opium Users Inform Intervention Strategies.

Front Nutr 2020 22;7:584585. Epub 2020 Dec 22.

Department of Nutrition, Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

Over 50 million people worldwide are estimated to use opioids, of which ~30 million use opiates (opium and its derivatives). Use of opiates has been associated with a variety of adverse complications such as neurological and behavioral outcomes, addiction, cancers, diabetes, and cardiovascular disease. While it is well known that opiates exert their neurobiological effects through binding with mu, kappa, and delta receptors to exert analgesic and sedative effects, mechanistic links to other health effects are not well understood. Our study focuses on the identification of biochemical perturbations in Golestan Cohort Study (GCS) opium users. We used untargeted metabolomics to evaluate the metabolic profiles of 218 opium users and 80 non-users participating in the GCS. Urine samples were obtained from adult (age 40-75) opium users living in the Golestan Province of Iran. Untargeted analysis of urine was conducted using a UPLC-Q-Exactive HFx Mass Spectrometry and a 700 MHz NMR Spectrometry. These GCS opium users had a significantly higher intake of tobacco and alcohol and a significantly decreased BMI compared with non-users. Metabolites derived from opium (codeine, morphine, and related glucuronides), nicotine, and curing or combustion of plant material were increased in opium users compared with non-users. Endogenous compounds which differentiated the opium users and non-users largely included vitamins and co-factors, metabolites involved in neurotransmission, Kreb's cycle, purine metabolism, central carbon metabolism, histone modification, and acetylation. Our study reveals biochemical perturbations in GCS opium users that are important to the development of intervention strategies to mitigate against the development of adverse effects of substance abuse.
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http://dx.doi.org/10.3389/fnut.2020.584585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783045PMC
December 2020

Association Between Serological Responses to Two Zoonotic Ruminant Pathogens and Esophageal Squamous Cell Carcinoma.

Vector Borne Zoonotic Dis 2021 Feb 29;21(2):125-127. Epub 2020 Oct 29.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.

Questionnaire data have linked contact with ruminants to the risk of esophageal squamous cell carcinoma (ESCC) in high-risk Asian populations. To better understand this observed association, we investigated exposure to two major zoonotic ruminant pathogens relative to ESCC risk. Using enzyme-linked immunosorbent assay, immunofluorescence assay, and microagglutination test assays, we measured immunoglobulin G anti- and anti- spp. antibodies in patients with ESCC ( = 177) and population-based controls ( = 177) matched by age, gender, and residence area from the Golestan case-control study in Iran. We found a similarly high seroprevalence of in ESCC cases and controls (75% and 80%, respectively), and a similarly low seroprevalence of spp. (0% and 0.6%, respectively). While documenting a high exposure to one of two zoonotic ruminant infections, this exposure failed to explain the observed association of ruminant contact and ESCC risk in this high-risk population.
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http://dx.doi.org/10.1089/vbz.2020.2668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876355PMC
February 2021

The Khuzestan Comprehensive Health Study (KCHS): Methodology and Profile of Participants.

Arch Iran Med 2020 10 1;23(10):653-657. Epub 2020 Oct 1.

Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Non-communicable diseases (NCDs) are the leading cause of death worldwide, with a disproportionally rising burden among low- and middle-income populations. While preventable risk factors highly contribute to this burden, population-based studies assessing these factors and the health status of these populations, are scarce.

Methods: The Khuzestan Comprehensive Health Study (KCHS)-a cross sectional study-was conducted between 2016-2019, including 30,506 Iranians aged 20 to 65 years, from 27 counties of Khuzestan province, southwest of Iran. KCHS aimed to provide a comprehensive health overview by investigating the prevalence and risk factors of NCDs and psychological disorders, along with viral hepatitis as a common communicable disease. Upon registration, 15 mL of blood and anthropometric measurements were obtained from participants. Afterwards, several interviewer-administered questionnaires were completed to gather data on demographics, socioeconomic status, sleep quality, physical activity, lifestyle habits, nutrition, and medical history.

Results: The mean ± SD age of participants was 41.7 ± 11.9 years. The majority were female (64.3%), of the Arab ethnicity (49%), married (83%), and urban residents (73.1%). About 70% had an educational level below high school diploma. Overall, 10.8%, 5.2%, and 2.8% of participants had used cigarettes, hookah, and drugs at least once in their lifetime, respectively. While body mass index and serum cholesterol levels were higher in females, blood pressure was higher in males (<0.001).

Conclusion: KCHS assessed many aspects of health in the Khuzestan province. In addition to develop a biobank along with a comprehensive dataset, KCHS will serve as a valuable infrastructure for future research.
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http://dx.doi.org/10.34172/aim.2020.82DOI Listing
October 2020

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

Nutr J 2020 09 28;19(1):108. Epub 2020 Sep 28.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.1186/s12937-020-00627-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523365PMC
September 2020

Methylated DNA Markers of Esophageal Squamous Cancer and Dysplasia: An International Study.

Cancer Epidemiol Biomarkers Prev 2020 Dec 18;29(12):2642-2650. Epub 2020 Sep 18.

Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background: Discovery of methylated DNA markers (MDM) of esophageal squamous cell carcinoma (ESCC) has sparked interest in assessing these markers in tissue. We evaluated MDMs in ESCC from three geographically and ethnically distinct populations, and explored the feasibility of assaying MDMs from DNA obtained by swallowed balloon devices.

Methods: MDMs were assayed in ESCC and normal tissues obtained from the populations of United States, Iran, and China, and from exfoliative cytology specimens obtained by balloons in a Chinese population. Areas under the receiver operating curve (AUC) of MDMs discriminating ESCC from normal tissues were calculated. Random forest prediction models were built, trained on U.S. cases and controls, and calibrated to U.S.-only controls (model 1) and three-country controls (model 2). Statistical tests were used to assess the relationship between dysplasia and MDM levels in balloons.

Results: Extracted DNA from 333 ESCC and 322 normal tissues was analyzed, in addition to archival DNA from 98 balloons. For ESCC, model 1 validated in Iranian and Chinese tissues with AUCs of 0.90 and 0.87, and model 2 yielded AUCs of 0.99, 0.96, and 0.94 in tissues from the United States, Iran, and China, respectively. In Chinese balloons, MDMs showed a statistically significant trend of increasing levels with increasing grades of dysplasia ( < 0.004).

Conclusions: MDMs accurately discriminate ESCC from normal esophagus in tissues obtained from high- and low-incidence countries. Preliminary data suggest that levels of MDMs assayed in DNA from swallowed balloon devices increase with dysplasia grade. Larger studies are needed to validate these results.

Impact: MDMs coupled with minimally invasive collection methods have the potential for worldwide application in ESCC screening.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710574PMC
December 2020

Opium use and the risk of head and neck squamous cell carcinoma.

Int J Cancer 2021 Mar 9;148(5):1066-1076. Epub 2020 Oct 9.

Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.

Scant evidence exists to support the association of opium use with head and neck cancer, limited to the larynx and oral cavity. In a multicenter case-control study-Iran Opium and Cancer study, we recruited 633 cases of head and neck squamous cell carcinoma (HNSCC) (254 lip and oral cavity, 54 pharynx, 327 larynx and 28 other subsites within the head and neck) and 3065 frequency-matched controls from April 2016 to April 2019. Odds ratios (ORs) for opium use and 95% confidence intervals (95% CIs) were obtained using mixed-effects logistic regression because of heterogeneity among centers. The adjusted OR (95% CI) for regular opium use was 3.76 (2.96-4.79) for all HNSCC combined. Strong dose-response effects were observed by frequency or amount of use, and duration of use. Regular opium uses significantly increased the risk of HNSCC of the pharynx, larynx and other subsites within the head and neck with OR (95% CI) of 2.90 (1.40-6.02), 6.55 (4.69-9.13) and 5.95 (2.41-14.71), respectively. The observed associations were significant even among never tobacco smokers (including cigarette and water-pipe smoking). Moreover, by the multiplicative interaction scale, the effect of opium use could be varied by cigarette smoking on HNSCC, 8.16 (6.20-10.74). For the first time, the current study showed opium users have an increased risk of several anatomic subsites of HNSCC.
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http://dx.doi.org/10.1002/ijc.33289DOI Listing
March 2021

Joint effect of diabetes and opiate use on all-cause and cause-specific mortality: the Golestan cohort study.

Int J Epidemiol 2021 Mar;50(1):314-324

Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.1093/ije/dyaa126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938504PMC
March 2021

Household Fuel Use and the Risk of Gastrointestinal Cancers: The Golestan Cohort Study.

Environ Health Perspect 2020 06 17;128(6):67002. Epub 2020 Jun 17.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Three billion people burn nonclean fuels for household purposes. Limited evidence suggests a link between household fuel use and gastrointestinal (GI) cancers.

Objectives: We investigated the relationship between indoor burning of biomass, kerosene, and natural gas with the subsequent risk of GI cancers.

Methods: During the period 2004-2008, a total of 50,045 Iranian individuals 40-75 years of age were recruited to this prospective population-based cohort. Upon enrollment, validated data were collected on demographics, lifestyle, and exposures, including detailed data on lifetime household use of different fuels and stoves. The participants were followed through August 2018 with loss.

Results: During the follow-up, 962 participants developed GI cancers. In comparison with using predominantly gas in the recent 20-y period, using predominantly biomass was associated with higher risks of esophageal [hazard ratio (HR): 1.89; 95% confidence interval (CI): 1.02, 3.50], and gastric HR: 1.83; 95% CI: 1.01, 3.31) cancers, whereas using predominantly kerosene was associated with higher risk of esophageal cancer (HR: 1.84; 95% CI: 1.10, 3.10). Lifetime duration of biomass burning for both cooking and house heating (exclusive biomass usage) using heating-stoves without chimney was associated with higher risk of GI cancers combined (10-y HR: 1.14; 95% CI: 1.07, 1.21), esophageal (10-y HR: 1.19; 95% CI: 1.08, 1.30), gastric (10-y HR: 1.11; 95% CI: 1.00, 1.23), and colon (10-y HR: 1.26; 95% CI: 1.03, 1.54) cancers. The risks of GI cancers combined, esophageal cancer, and gastric cancer were lower when biomass was burned using chimney-equipped heating-stoves (strata difference , 0.003, and 0.094, respectively). Duration of exclusive kerosene burning using heating-stoves without chimney was associated with higher risk of GI cancers combined (10-y HR: 1.05; 95% CI: 1.00, 1.11), and esophageal cancer (10-y HR: 1.14; 95% CI: 1.04, 1.26).

Discussion: Household burning of biomass or kerosene, especially without a chimney, was associated with higher risk of some digestive cancers. Using chimney-equipped stoves and replacing these fuels with natural gas may be useful interventions to reduce the burden of GI cancers worldwide. https://doi.org/10.1289/EHP5907.
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http://dx.doi.org/10.1289/EHP5907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299082PMC
June 2020

Opium use and subsequent incidence of cancer: results from the Golestan Cohort Study.

Lancet Glob Health 2020 05;8(5):e649-e660

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Digestive Disease Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Evidence is emerging for a role of opiates in various cancers. In this study, we aimed to investigate the association between regular opium use and cancer incidence.

Methods: This study was done in a population-based cohort of 50 045 individuals aged 40-75 years from northeast Iran. Data on participant demographics, diet, lifestyle, opium use, and different exposures were collected upon enrolment using validated questionnaires. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% CIs for the association between opium use and different cancer types.

Findings: During a median 10 years of follow-up, 1833 participants were diagnosed with cancer. Use of opium was associated with an increased risk of developing all cancers combined (HR 1·40, 95% CI 1·24-1·58), gastrointestinal cancers (1·31, 1·11-1·55), and respiratory cancers (2·28, 1·58-3·30) in a dose-dependent manner (p<0·001). For site-specific cancers, use of opium was associated with an increased risk of developing oesophageal (1·38, 1·06-1·80), gastric (1·36, 1·03-1·79), lung (2·21, 1·44-3·39), bladder (2·86, 1·47-5·55), and laryngeal (2·53, 1·21-5·29) cancers in a dose-dependent manner (p<0·05). Only high-dose opium use was associated with pancreatic cancer (2·66, 1·23-5·74). Ingestion of opium (but not smoking opium) was associated with brain (2·15, 1·00-4·63) and liver (2·46, 1·23-4·95) cancers in a dose-dependent manner (p<0·01). We observed consistent associations among ever and never tobacco users, men and women, and individuals with lower and higher socioeconomic status.

Interpretation: Opium users have a significantly higher risk of developing cancers in different organs of the respiratory, digestive, and urinary systems and the CNS. The results of this analysis show that regular use of opiates might increase the risk of a range of cancer types.

Funding: World Cancer Research Fund International, Cancer Research UK, Tehran University of Medical Sciences, US National Cancer Institute, International Agency for Research on Cancer.
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http://dx.doi.org/10.1016/S2214-109X(20)30059-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196888PMC
May 2020

The first clusters of Middle East respiratory syndrome coronavirus in Oman: Time to act.

J Infect Public Health 2020 May 16;13(5):679-686. Epub 2020 Apr 16.

Royal Hospital, Ministry of Health, Oman. Electronic address:

Introduction: Middle East respiratory syndrome coronavirus (MERS-CoV), is an emerging infectious disease of growing global importance. This review describes the latest MERS-CoV clusters and the first cases of nosocomial transmission within health care facilities in Oman. We have highlighted lessons learned and proposed steps to prevent healthcare-associated infections.

Methods: A descriptive analysis of MERS-CoV cases was conducted between January 23 and February 16, 2019. The data from officials and other published sources used.

Results: Thirteen laboratory-confirmed cases of MERS-CoV were reported from three simultaneous clusters from two governorates without an epidemiological link between the clusters. Two clusters were reported from North Al Batinah Governorate, with nine cases (69%) and 1 cluster from South Ash Sharqiyah Governorate with four cases (31%). In total, four deaths were reported (case fatality rate 31%). Four cases (31%) reported were household contacts from the first cluster, 3 (23%) were nosocomial transmission in health care facilities (two for first and one from the second cluster) and 7 (54%) were community-acquired cases.

Conclusions: The first local clusters of MERS-CoV reported with evidence suggestive of healthcare and household-associated transmission. Early diagnosis and strict implementation of infection control measures remain fundamental in preventing and managing MERS-CoV infection.
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http://dx.doi.org/10.1016/j.jiph.2020.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162632PMC
May 2020

Urinary TERT promoter mutations are detectable up to 10 years prior to clinical diagnosis of bladder cancer: Evidence from the Golestan Cohort Study.

EBioMedicine 2020 Mar 17;53:102643. Epub 2020 Feb 17.

International Agency for Research on Cancer (IARC), Lyon, France. Electronic address:

Background: Detecting pre-clinical bladder cancer (BC) using urinary biomarkers may provide a valuable opportunity for screening and management. Telomerase reverse transcriptase (TERT) promoter mutations detectable in urine have emerged as promising BC biomarkers.

Methods: We performed a nested case-control study within the population-based prospective Golestan Cohort Study (50,045 participants, followed up to 14 years) and assessed TERT promoter mutations in baseline urine samples from 38 asymptomatic individuals who subsequently developed primary BC and 152 matched controls using a Next-Generation Sequencing-based single-plex assay (UroMuTERT) and droplet digital PCR assays.

Findings: Results were obtained for 30 cases and 101 controls. TERT promoter mutations were detected in 14 pre-clinical cases (sensitivity 46·67%) and none of the controls (specificity 100·00%). At an estimated BC cumulative incidence of 0·09% in the cohort, the positive and negative predictive values were 100·00% and 99·95% respectively. The mutant allelic fractions decreased with the time interval from urine collection until BC diagnosis (p = 0·033) but the mutations were detectable up to 10 years prior to clinical diagnosis.

Interpretation: Our results provide the first evidence from a population-based prospective cohort study of the potential of urinary TERT promoter mutations as promising non-invasive biomarkers for early detection of BC. Further studies should validate this finding and assess their clinical utility in other longitudinal cohorts.

Funding: French Cancer League, World Cancer Research Fund International, Cancer Research UK, Tehran University of Medical Sciences, the International Agency for Research on Cancer, and the U.S. National Cancer Institute.
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http://dx.doi.org/10.1016/j.ebiom.2020.102643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118568PMC
March 2020

Opiate and Tobacco Use and Exposure to Carcinogens and Toxicants in the Golestan Cohort Study.

Cancer Epidemiol Biomarkers Prev 2020 03 8;29(3):650-658. Epub 2020 Jan 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Background: There is little information on human exposure to carcinogens and other toxicants related to opiate use, alone or in combination with tobacco.

Methods: Among male participants of the Golestan Cohort Study in Northeast Iran, we studied 28 never users of either opiates or tobacco, 33 exclusive cigarette smokers, 23 exclusive users of smoked opiates, and 30 opiate users who also smoked cigarettes (dual users; 21 smoked opiates and 9 ingested them). We quantified urinary concentrations of 39 exposure biomarkers, including tobacco alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC), and used decomposition to parse out the share of the biomarker concentrations explained by opiate use and nicotine dose.

Results: Dual users had the highest concentrations of all biomarkers, but exclusive cigarette smokers and exclusive opiate users had substantially higher concentrations of PAH and VOC biomarkers than never users of either product. Decomposition analysis showed that opiate use contributed a larger part of the PAH concentrations than nicotine dose, and the sum of 2- and 3-hydroxyphenanthrene (∑-phe) resulted almost completely from opiate use. Concentrations of most VOC biomarkers were explained by both nicotine dose and opiate use. Two acrylamide metabolites, a 1,3-butadiene metabolite and a dimethylformamide metabolite, were more strongly explained by opiate use. Acrylamide metabolites and ∑-phe were significantly higher in opiate smokers than opiate eaters; other biomarkers did not vary by the route of opiate intake.

Conclusions: Both cigarette smokers and opiate users (by smoking or ingestion) were exposed to many toxicants and carcinogens.

Impact: This high exposure, particularly among dual opiate and cigarette users, can have a substantial global public health impact.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839071PMC
March 2020

Peripheral blood blast rate of clearance is an independent predictor of clinical response and outcomes in acute myeloid leukaemia.

Br J Haematol 2020 03 5;188(6):881-887. Epub 2019 Dec 5.

Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.

The day 14 bone marrow aspirate and biopsy (D14BM) is regularly used to predict achievement of complete remission (CR) with induction chemotherapy in acute myeloid leukemia (AML), however its utility has been questioned. Clearance of peripheral blood blasts (PBB) may serve as an early measure of chemosensitivity. PBB rate of clearance (PBB-RC) was calculated for treatment-naive AML patients (n = 164) undergoing induction with an anthracycline and cytarabine (7+3) and with detectable PBB at diagnosis. PBB-RC was defined as the percentage of the absolute PBB count on the day of diagnosis that was cleared with each day of therapy, on average, until D14 or day of PBB clearance. Each 5% increase in PBB-RC approximately doubled the likelihood of D14BM clearance (OR = 1·81; 95% CI: 1·24-2·64, P < 0·005). PBB-RC was also associated with improved CR rates (OR per 5% = 1·97; 95% CI: 1·27-3·01, P < 0·005) and overall survival (OS) [hazard ratio (HR) per 5% = 0·67; 95% CI: 0·52-0·87]. African American patients had poorer OS adjusted for PBB-RC (HR = 2·18; 95% CI: 1·13-4·23), while race was not associated with D14BM or CR rate. PBB-RC during induction chemotherapy is predictive of D14BM clearance, CR, and OS, and can therefore serve as a prognostic marker for clinical outcomes in AML.
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http://dx.doi.org/10.1111/bjh.16261DOI Listing
March 2020

An Exploratory Study of Units of Reporting Opium Usein Iran: Implications for Epidemiologic Studies.

Arch Iran Med 2019 10 1;22(10):541-545. Epub 2019 Oct 1.

Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.

Background: Measuring the amount of opium use is a challenge in epidemiologic studies. Self-report of amount of opium use at each consumption, widely used in the literature, usually fails to provide a good estimate. The purpose of this study is to systematically study the perceived weight units of reported opium use in Iran, and compare them to the standardized units of weight measurement.

Methods: An exploratory descriptive study was conducted in six major cities of Iran. Study participants were interviewed and asked to use a Play-Doh-like material to demonstrate the amount of opium they use. To obtain an estimate of the weight of the material used, we multiplied the volume by the density of the opium product. We experimentally determined the density of the commonly used opium products. We used medians and inter-quartile ranges (IQRs) to report the typical amount of each unit.

Results: A total of 108 individuals participated in this study. The most frequently reported unit was "gram"; the median perceived weight for one gram (g) of opium was 0.24 (IQR: 0.16) g. The second most commonly used unit was nokhod with a median of 0.16 (IQR: 0.16) g, followed by mesghaal and hab/habeh, which were 1.28 (IQR: 0.81) and 0.16 (IQR: 0.16) g, respectively. The median perceived weight of mesghaal and gram in the studied cities was less than the expected standardized values.

Conclusion: In conclusion, the reported amount of opium use is highly inaccurate and unreliable, and is mainly subject to underestimation.
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October 2019

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

Lancet 2019 08;394(10199):672-683

Digestive Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Liver and Pancreaticobiliary Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

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; p=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.
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http://dx.doi.org/10.1016/S0140-6736(19)31791-XDOI Listing
August 2019

Author's reply to comment on "A prospective study of tea drinking temperature…" by Islami et al.

Int J Cancer 2019 11 13;145(10):2888-2889. Epub 2019 Aug 13.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.1002/ijc.32600DOI Listing
November 2019

Comparing Anthropometric Indicators of Visceral and General Adiposity as Determinants of Overall and Cardiovascular Mortality.

Arch Iran Med 2019 06 1;22(6):301-309. Epub 2019 Jun 1.

Digestive Diseases Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: It is unclear which anthropometric obesity indicator best predicts adverse health outcomes. This study aimed to investigate the association of body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), and hip-adjusted WC with all-cause and cardiovascular mortality.

Methods: 50045 people aged 40-75 (58% women, median BMI: 26.3 kg /m2 ) participated in the population-based Golestan Cohort Study. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for the association of obesity indicators with mortality. We also examined the association of these indicators with intermediate outcomes, including hypertension, blood glucose, dyslipidemia, carotid atherosclerosis, nonalcoholic fatty liver, and visceral abdominal fat.

Results: After a median follow-up of 10.9 years (success rate: 99.1%), 6651 deaths (2778 cardiovascular) occurred. Comparing 5th to the 1st quintile, HRs (95% CIs) for all-cause and cardiovascular mortality were 1.12 (1.02-1.22) and 1.59 (1.39-1.83) for BMI, 1.16 (1.07-1.27) and 1.66 (1.44-1.90) for WC, 1.28 (1.17-1.40) and 1.88 (1.63-2.18) for WHtR, 1.44 (1.32-1.58) and 2.04 (1.76-2.36) for WHR, and 1.84 (1.62-2.09) and 2.72 (2.23-3.32) for hip-adjusted WC, respectively. Hip-adjusted WC had the strongest associations with the intermediate outcomes.

Conclusion: Indicators of visceral adiposity (e.g., hip-adjusted WC) were much stronger predictors of overall and cardiovascular mortality than were indicators of general adiposity (e.g., BMI). The full-strength effect of visceral adiposity becomes apparent only when both WC, as a risk factor, and hip circumference, as a protective factor, are individually and simultaneously taken into consideration.
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June 2019

Substitution of dietary protein sources in relation to colorectal cancer risk in the NIH-AARP cohort study.

Cancer Causes Control 2019 Oct 20;30(10):1127-1135. Epub 2019 Jul 20.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Purpose: To evaluate the substitution effect of plant for animal protein with risk of CRC in the large prospective National Institutes of Health-AARP cohort study.

Methods: Protein intake was assessed at baseline using a food frequency questionnaire. HRs and 95% CIs were estimated using multivariable adjusted hazard ratios from Cox proportional hazards models. We used a substitution model with total protein intake held constant, so that an increase in plant protein was offset by an equal decrease in animal protein.

Results: Among 489,625 individuals, we identified 8,995 incident CRCs after a median follow-up of 15.5 years. Substituting plant protein for animal protein was associated with a reduced risk of CRC (HR for highest vs. lowest fifth 0.91; 95% CI 0.83-0.99). This reduction in CRC risk appeared to be primarily due to substituting plant protein for red meat protein (HR 0.89; 95% CI 0.81-0.97), not white meat protein (HR 0.96; 95% CI 0.88-1.05) or other animal protein (HR 0.94; 95% CI 0.86-1.03). When further evaluated by source, reduction in CRC risk was limited to the substitution of protein from bread, cereal, and pasta for red meat protein (HR 0.86; 95% CI 0.80-0.93); this association was stronger for distal colon (HR 0.78; 95% CI 0.67-0.90) and rectal cancer (HR 0.79; 95% CI 0.68-0.91) but null for proximal colon (HR 0.99; 95% CI 0.88-1.11).

Conclusions: This study shows that substituting plant protein for animal protein, especially red meat protein, is associated with a reduced risk of CRC, and suggests that protein source impacts CRC risk.
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http://dx.doi.org/10.1007/s10552-019-01210-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736766PMC
October 2019

Nut and Peanut Butter Consumption and Mortality in the National Institutes of Health-AARP Diet and Health Study.

Nutrients 2019 Jul 2;11(7). Epub 2019 Jul 2.

Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.

Although previous studies have shown inverse associations between nut consumption and mortality, the associations between nut consumption and less common causes of mortality have not been investigated. Additionally, about 50% of peanut consumption in the US is through peanut butter but the association between peanut butter consumption and mortality has not been thoroughly evaluated. The National Institutes of Health-AARP (NIH-AARP) Diet and Health Study recruited 566,398 individuals aged 50-71 at baseline in 1995-1996. A food-frequency questionnaire was used to evaluate nut and peanut butter consumption. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals for mortality using the non-consumers as reference groups and three categories of consumption. After excluding subjects with chronic diseases at baseline, there were 64,464 deaths with a median follow-up time of 15.5 years. We observed a significant inverse association between nut consumption and overall mortality (HR = 0.78, 95% CI = 0.76, 0.81, ≤ 0.001). Nut consumption was significantly associated with reduced risk of cancer, cardiovascular, respiratory, infectious, renal and liver disease mortality but not with diabetes or Alzheimer's disease mortality. We observed no significant associations between peanut butter consumption and all-cause (HR = 1.00, 95% CI = 0.98, 1.04, = 0.001) and cause-specific mortality. In a middle-aged US population, nut intake was inversely associated with all-cause mortality and certain types of cause-specific mortality. However, peanut butter consumption was not associated with differential mortality.
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http://dx.doi.org/10.3390/nu11071508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682967PMC
July 2019

Potato consumption and the risk of overall and cause specific mortality in the NIH-AARP study.

PLoS One 2019 7;14(5):e0216348. Epub 2019 May 7.

Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, United States of America.

Background: Potato consumption has been hypothesized to be associated with higher risk of hypertension, diabetes, and colorectal cancer.

Objective: The aim of this study was to examine the association between potato consumption and the risk of overall and cause specific mortality in the large prospective National Institutes of Health-AARP (NIH-AARP) Study.

Design: The NIH-AARP study recruited 566,407 persons, aged 50-72 years in 1995-1996. We excluded subjects that reported a history of chronic disease at baseline. Potato consumption data from a validated food frequency questionnaire completed at baseline was used in Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for overall and cause specific mortality. Final models were adjusted for potential risk factors for mortality.

Results: Among 410,701 participants included in this analysis, 76,921 persons died during the 15.6 years of follow-up. Eating baked, boiled, or mashed potatoes, French fries or potato salad seven or more times per week was associated with higher risk of overall mortality, in models adjusted only for age and sex (HR C4 vs C1 = 1.17, 95%CI = 1.13, 1.21). These results were attenuated in fully adjusted models (HR C4 vs C1 = 1.02, 95%CI = 0.97, 1.06). Potato consumption was not associated with risk of mortality caused by cancer (HR C4 vs C1 = 1.04, 95%CI = 0.97, 1.11), heart disease (HR C4 vs C1 = 1.00, 95%CI = 0.93, 1.09), respiratory disease (HR C4 vs C1 = 1.16, 95%CI = 0.99, 1.37), or diabetes (HR C4 vs C1 = 0.91, 95%CI = 0.71, 1.19). We tested for an association with different preparation methods and found limited evidence for differences by preparation method. The only statistically significant association was that for French fry consumption with cancer-related mortality (HR C4 vs C1 = 1.27, 95%CI = 1.02, 1.59), a finding for which uncontrolled confounding could not be ruled out.

Conclusion: We find little evidence that potato consumption is associated with all-cause or cause-specific mortality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216348PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504095PMC
January 2020