This study investigated the associations between specific polymorphisms in the Interleukin-10 (IL-10), Interleukin-18 (IL-18), Interleukin-1 beta (IL-1β), and Tumor Necrosis Factor-alpha (TNF-α) cytokine genes and susceptibility to chronic hepatitis B infection (CHB) in Iranian families with a history of the disease. This cross-sectional study involved 90 CHB patients, 18 individuals with Recovered hepatitis B virus (HBV) infection, and 30 healthy intrafamilial controls matched for age and sex. Genotyping of the IL-10 (−1082 G > A), IL-18 (−137 G > C), IL-1β (−511 C > T), and TNF-α (−308 G > A) polymorphisms was conducted via polymerase chain reaction with sequence-specific primers (PCR-SSP). Associations with CHB susceptibility were assessed via multivariate logistic regression adjusted for age and sex across multiple genetic models. To address potential non-independence of observations from the same family, we conducted a sensitivity analysis using a generalized estimating equation (GEE) approach with an exchangeable correlation structure, clustering by family. A significant association was identified between the IL-10–1082 AA genotype and CHB. This genotype was present in 84.4

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

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

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

Diet and nutrition are critical factors influencing cancer, the second leading cause of death worldwide. This study evaluated dietary risk factors and cancer mortality. 49,773 participants aged 40-75 years from the Golestan Cohort Study (GCS) were followed for a median of 15 years. Dietary intake was assessed using a validated food frequency questionnaire. Cox proportional hazard models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), while population attributable fractions (PAFs) quantified the impact of reducing dietary risk factors. Low fruit intake accounted for 4.7% (95% CI: 0.5-8.7%) of all cancer deaths and 4.91% (95% CI: 0-9.85%) of male cancer deaths. It contributed to 23.5% (95% CI: 4.7-38.59%) of pancreatic cancer mortality in both sexes and 29.36% (95% CI: 5.15-47.38%) of male pancreatic cancer deaths. Low omega-3 intake increased esophageal and gastric cancer mortality risks, with PAFs of 21.65% (95% CI: 1.14-37.9%) and 21.46% (95% CI: 2.81-36.53%), respectively. In females, low omega-3 intake accounted for 38.68% (95% CI: 4.05-60.81%) of gastric cancer deaths. Low fruit and omega-3 consumption elevated cancer mortality risk. Community- and individual-level interventions are essential to enhance nutrient intake and reduce cancer mortality.

Background and objective Two decades ago, an international initiative (GEMINI) was launched in a high-risk, low-resource region in Northeast Iran, aiming to investigate incidence, etiology, early detection, and treatment of esophageal squamous cell carcinoma (ESCC). An earlier report from this area, highlighted poor ESCC survival rates, with a 5-year survival probability of 3.3% and the median survival time of 7 months. Our study assesses whether ESCC survival has improved since the implementation of the GEMINI initiative in this region. Material and methods 490 adult patients with histologically-confirmed ESCC were recruited from the Atrak clinic, Golestan, Iran, between 2007 and 2018. At recruitment, information on demographics and various exposures were collected. Active (telephone surveys) and passive (linkage to Golestan population-based cancer and death registries) follow-up methods were used to determine patients’ vital status though March 2019. Survival estimates were obtained by Kaplan-Meier method and Cox proportional hazards regression models. Results Over the study period 340 deaths were recorded. Five-year ESCC survival probability was 23% (95% Confidence Interval: 19% to 28%), and the median survival time was 19 months. Five-year survival probability was higher among individuals who were younger (35% in <60-year-olds vs. 12% for >70-year-olds, p<0.001), educated (34% vs. 21% for no formal education, p = 0.027), never used opium (28% vs. 15%, p = 0.0016), and received cancer treatment (37% vs. 4%, p<0.001). In the adjusted models, a higher hazard of death was associated with older age [HR for each 10-year increase = 1.36 (95% CI = 1.22 to 1.51)], Turkman ethnicity [HR = 1.35 (95%CI: 1.07 to 1.70)], opium use [HR = 1.53 (95%CI: 1.20 to 1.94)],and receiving no cancer treatment [HR = 5.81 (95%CI: 3.97 to 8.52)]. Conclusion Over the last two decades, ESCC survival in this population has significantly improved, highlighting the potential of enhancing healthcare infrastructure and ensuring access to affordable medical care in resource-limited, high-risk regions. Older age at diagnosis, Turkman ethnicity, opium use, and untreated cases (indicative of advanced disease at diagnosis) were identified as the main ESCC prognostic factors in this population.

The relationship between kidney and vascular health is acknowledged, but detailed information is still missing. This study examines the relationship of estimated glomerular filtration rate (eGFR) and carotid intima media thickness, providing insights into the association between atherosclerosis and kidney function. Participants older than 50 years of age who were part of the PolyIran-L study, a trial nested in the Golestan Cohort Study, were included. The maximal intima media thickness of both common carotid arteries was evaluated using B-mode ultrasonography. Four different cut-off values for abnormal carotid intima media thickness were considered. Correlation of carotid intima media thickness and eGFR was assessed with linear correlation and multivariable binary logistic regression models after adjusting for several confounders. In total, 1562 participants (750 females, 48

Background Studying carcinogens in tobacco and nontobacco sources may be key to understanding the pathogenesis and geographic distribution of esophageal cancer.Methods The Golestan Cohort Study has been conducted since 2004 in a region with high rates of esophageal squamous cell carcinoma. For this nested study, the cases comprised of all incident cases by January 1, 2018; controls were matched to the case by age, sex, residence, time in cohort, and tobacco use. We measured urinary concentrations of 33 exposure biomarkers of nicotine, polycyclic aromatic hydrocarbons, volatile organic compounds, and tobacco-specific nitrosamines. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for associations between the 90th vs the 10th percentiles of the biomarker concentrations and incident esophageal squamous cell carcinoma.Results Among individuals who did not currently use tobacco (148 cases and 163 controls), 2 acrolein metabolites, 2 acrylonitrile metabolites, 1 propylene oxide metabolite, and one 1,3-butadiene metabolite were significantly associated with incident esophageal squamous cell carcinoma (adjusted odds ratios between 1.8 and 4.3). Among tobacco users (57 cases and 63 controls), metabolites of 2 other volatile organic compounds (styrene and xylene) were associated with esophageal squamous cell carcinoma (OR = 6.2 and 9.0, respectively). In tobacco users, 2 tobacco-specific nitrosamines (NNN and N'-Nitrosoanatabine) were also associated with esophageal squamous cell carcinoma. Suggestive associations were seen with some polycyclic aromatic hydrocarbons (especially 2-hydroxynaphthalene) in nonusers of tobacco products and other tobacco-specific nitrosamines in tobacco users.Conclusion These novel associations based on individual-level data and samples collected many years before cancer diagnosis, from a population without occupational exposure, have important public health implications.

Background:Metabolic dysfunction-associated fatty liver disease (MAFLD) is a rising global public health concern. It has been demonstrated that its prevalence and characteristics vary by region and racial/ethnicity. We aimed to investigate the prevalence of MAFLD and its characteristics among Turkmen and non-Turkmen ethnic groups in a multiethnic population region of Iran. Methods:In this cross-sectional study, we analyzed baseline data for 1614 participants, aged above 50 years, from the PolyIran-Liver trial who were randomly selected from Gonabad city and determined the prevalence of MAFLD and its demographic and metabolic disorders for both the Turkmen and non-Turkmen ethnic groups. Multivariate binary logistic regressions were applied to identify MAFLD-associated factors for men and women separately for the Turkmen and non-Turkmen populations. Results:The mean (SD) age of the participants was 59.1(6.7) years. Of the participants, 51.5% (n=831) were men, and 52.9% (n=854) were Turkmen. The prevalence of MAFLD among the overall study population was 39.8% (n=614). It was more common among women (45.8% vs. 34.1% in men, P<0.001), non-Turkmens (43.9% vs. 36.1% in Turkmens, P<0.001), and at age 50-64 (41.5% vs.36.1% in age≥65 P=0.004). The fully adjusted multivariate analysis in sex strata exhibited an independent negative association between Turkmen ethnicity only among men but not among women. The increased waist circumference (WC) was the most common metabolic disorder, observed in more than 95.5% of patients with MAFLD (P<0.001). Multivariate analysis in sex/ethnic strata with adjustment for potential confounders revealed an independent association of MAFLD with increased WC, insulin resistance, impaired fasting glucose/diabetes type 2, and high alanine aminotransferase (ALT) among women in both ethnic groups while with elevated triglyceride (TG) only among Turkmen and high body mass index (BMI) only among non-Turkmen women. Increased WC had the strongest independent association with MAFLD among women and the highest odds ratio (OR) with MAFLD in Turkmen women (OR: 6.10; 95% CI 1.56-23.86 vs. 4.80 in non-Turkmen women). Among men, MAFLD was independently associated with insulin resistance, high BMI, and high ALT in both ethnic groups and elevated TG only in non-Turkmen men (all P<0.001). Insulin resistance had the strongest independent OR with MAFLD among men with similar size in both ethnic groups (4.68 [95% CI 2.56-8.55]) in non-Turkmen men and 4.37 (95% CI 2.27-8.42 in Turkmen men). Conclusion:This study revealed the high prevalence of MAFLD with a sex and ethnic disparity in the middle-aged population of Gonabad city. Further research is needed to understand the factors contributing to the higher prevalence of MAFLD in this region, particularly in women. Furthermore, considering the diverse ethnic population of Iran, it is suggested that future investigations on the sex and ethnic aspects of MAFLD in the Iranian population be conducted to provide targeted prevention strategies better suited for the Iranian population.

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.

Chronic hepatitis B (CHB) infection is influenced by both virological and host factors. A total of 5,920 CHB patients were classified into four groups based on HBV seromarkers: three-generation families (CHB grandmother, mother, and child), two-generation families (CHB mother/child pairs), individuals recovered from HBV infection, and a control group. Serological markers, viral load, liver function tests (LFT), HBV mutations, HLA-DQ variations, cytokine polymorphisms, and liver stiffness measurements (LSM) were analyzed using FibroScan. Point mutations in genes such as core/pre-core (G1896A/G1899A), polymerase (H248N, H267Q, N263D), S (G145R, S143L), and X (C1500T, T1464C) were observed in 30

Background: Volatile organic compounds (VOCs) are major components of air pollution and tobacco smoke, two known risk factors for cardiovascular diseases. VOCs are ubiquitous in the environment and originate from a wide range of sources, including the burning of biomass, fossil fuels, and consumer products. Direct evidence for associations between specific VOCs and ischemic heart disease (IHD) mortality in the general population is scarce. Methods: In a case-cohort study (stratified by age groups, sex, residence, and tobacco smoking), nested within the population-based Golestan cohort study ( n = 50,045, 40 -75 years, 58% women, enrollment: 2004 -2008) in northeastern Iran, we measured urinary concentrations of 20 smoking-related VOC biomarkers using ultra highperformance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. We calculated hazard ratio (HR) and 95% confidence interval (CI) for their associations with IHD mortality during follow-up to 2018, using Cox regression models adjusted for age, ethnicity, education, marital status, body mass index, physical activity, wealth, and urinary cotinine. Results: There were 575 non-cases from random subcohort and 601 participants who died from IHD, mean (standard deviation) age, 58.2 (9.3) years, with a median of 8.4 years follow-up. Significant associations [3rd vs. 1st tertile, HR (95% CI), P for trend] were observed between biomarkers of acrylamide [1.68(1.05,2.69), 0.025], acrylonitrile [2.06(1.14,3.72), 0.058], acrolein [1.98(1.30,3.01), 0.003 and 2.44(1.43,4.18), 0.002], styrene/ ethylbenzene [1.83(1.19,2.84), 0.007 and 1.44(1.01,2.07), 0.046], dimethylformamide/methylisocyanate [2.15 (1.33,3.50), 0.001], and 1,3butadiene [2.35(1.52,3.63), <0.001] and IHD mortality. These associations were independent of tobacco smoking, and they were only present in the non-smoking subgroup. Conclusion: Our findings provide direct evidence for associations between exposure to several VOCs with widespread household and commercial use and IHD mortality many years after these exposures. These results highlight the importance of VOC exposure in the general population as a risk factor for cardiovascular diseases and underline the importance of bio-monitoring non-tobacco VOC exposure.

Background: While cardiovascular disease (CVD) polypills have demonstrated significant benefits in preventing CVD events by managing CVD risk factors and improving patient adherence, their effects on blood glucose levels, an important risk factor for CVD, remain unknown. Methods: We analyzed data from the PolyIran-Liver trial, which involved 1,508 participants aged 50 and above. Of these, 787 were randomly assigned to receive a polypill (consisting of aspirin, atorvastatin, hydrochlorothiazide, and valsartan), while 721 received usual care as the control group over a five-year period. The aim was to determine whether there were any significant differences in fasting blood sugar (FBS) levels between the two groups at baseline, middle, and end of the study. The data analysis focused on three subgroups: participants with diabetes, those with metabolic syndrome (MetS) but without diabetes, and participants without diabetes or MetS. Results: Of the total studied population, with a mean age of 59±6.7 years, 328(22%) were identified with diabetes, 371 (25%) with MetS but without diabetes, and 809 (54%) without diabetes or MetS. We observed a trend of rising FBS levels until month 30, followed by a subsequent decline at month 60. Participants in the polypill group exhibited lower FBS levels than the control group at both time points, with statistically significant differences in all three subgroups at month 30 and in the MetS-without diabetes at month 60 (mean difference: -9.3 mg/dl, 95% CI: 13.9 to -4.6). Conclusion: The polypill used in this study may have the potential to delay the onset of diabetes in patients with MetS more effectively than in the general population. However, its beneficial effects on the blood sugar levels of diabetic individuals require further investigation.

BackgroundCardiovascular diseases (CVDs) are the leading causes of global mortality and disability. Several studies demonstrated that metabolic risk factors increase cardiovascular mortality. The aim of this study is to examine CVDs deaths and population attributable fractions (PAFs) of their metabolic risk factors in Iran.MethodsThis is a study on 8,621 participants aged 45-75 years and older, recruited in the repeated measurement phase of the Golestan cohort study (GCS) in northeast of Iran. The Cox proportional hazards model was used to determine the adjusted hazard ratios (HRs). PAFs were calculated to enumerate CVDs mortality avoidable in the population if metabolic risk factors were eliminated.ResultsThe mortality of CVDs was attributable to metabolic factors, including high waist circumference (PAF, 28%, [95% CI: 16%-38%]), high fasting blood sugar (FBS) (20%, [15%-24%]), overweight and obesity (19%, [8%-28%]), high blood pressure (16%, [11%-21%]), high low-density lipoprotein cholesterol (LDL-C) (8%, [1%-15%]), and high triglyceride (TG) (7%, [3%-11%]). Collectively, these metabolic risk factors accounted for 50% of CVDs deaths. Females (67%, [50%-78%]) had a higher joint PAF of metabolic risk factors compared to males (43%, [27%-55%]).ConclusionsThe pattern of CVDs mortality attributable to metabolic risk factors in this study is not the same as similar studies in other parts of the world and previous studies in Iran. It is imperative that CVDs risk factors be specifically evaluated and addressed in various populations due to variety in geographical and temporal patterns in contribution of metabolic risk factors to CVD mortality.

BACKGROUND:Environmental risk factors are significant contributors to cancer mortality, which are neglected. PURPOSE:This study aimed to estimate the population attributable fraction of cancer mortality due to the environmental risk factors. METHODS:Golestan cohort study is a population-base cohort on 50045 participants between 40-75 with about 18 years of follow up. We detected 2,196 cancer mortality and applied a multiple Cox model to compute the hazard ratio of environmental risk factor on all cancer and cancer-specific mortality. The population attributable fraction was calculated, accordingly. RESULTS:Biomass fuels for cooking, as an indoor air pollution, increased the risk of colorectal, esophageal, gastric cancer, and all-cancer mortality by 84%, 66%, 37%, and 17% respectively. Using gas for cooking, particularly in rural areas, could save 6% [Population Attributable Fraction: 6.36(95%CI: 1.82, 10.70)] of esophageal cancer, 3% [Population Attributable Fraction: 3.43 (0, 7.33)] of gastric cancer, and 6% [Population Attributable Fraction: 6.25 (1.76, 13.63)] of colorectal cancer mortality. Using a healthy tap water source could save 5% [Population Attributable Fraction:5.50(0, 10.93)] of esophageal cancer mortality, particularly in rural areas. There was no significant association between indoor air pollution for heating purposes and animal contact with cancer mortality. CONCLUSION:Considering the results of this study, eliminating solid fuel for most daily usage, among the population with specific cancer types, is required to successfully reduce cancer related mortality. Adopting appropriate strategies and interventions by policymakers such as educating the population, allocating resources for improving the healthy environment of the community, and cancer screening policies among susceptible populations could reduce cancer related mortalities.

You have accessJournal of UrologyCME1 Apr 2023MP22-19 URINARY COMPREHENSIVE GENOMIC PROFILING PREDICTS UROTHELIAL CANCER UP TO 12 YEARS AHEAD OF CLINICAL DIAGNOSIS. AN EXPANDED ANALYSIS OF THE GOLESTAN COHORT STUDY Yair Lotan, Keyan Salari, Adam Feldman, Debasish Sundi, Jason J Lee, Gabrielle DiFiore, Hossein Poustchi, Masoud Khoshnia, Gholamreza Roshandel, Arash Etemadi, Mahdi Goudarzi, Peter S. Lentz, Kevin G. Phillips, Vincent T. Bicocca, Theresa M. Koppie, Joe W. Gray, Trevor Levin, Reza Malekzadeh, Mahdi Sheikh, and Florence Le Calvez-Kelm Yair LotanYair Lotan More articles by this author , Keyan SalariKeyan Salari More articles by this author , Adam FeldmanAdam Feldman More articles by this author , Debasish SundiDebasish Sundi More articles by this author , Jason J LeeJason J Lee More articles by this author , Gabrielle DiFioreGabrielle DiFiore More articles by this author , Hossein PoustchiHossein Poustchi More articles by this author , Masoud KhoshniaMasoud Khoshnia More articles by this author , Gholamreza RoshandelGholamreza Roshandel More articles by this author , Arash EtemadiArash Etemadi More articles by this author , Mahdi GoudarziMahdi Goudarzi More articles by this author , Peter S. LentzPeter S. Lentz More articles by this author , Kevin G. PhillipsKevin G. Phillips More articles by this author , Vincent T. BicoccaVincent T. Bicocca More articles by this author , Theresa M. KoppieTheresa M. Koppie More articles by this author , Joe W. GrayJoe W. Gray More articles by this author , Trevor LevinTrevor Levin More articles by this author , Reza MalekzadehReza Malekzadeh More articles by this author , Mahdi SheikhMahdi Sheikh More articles by this author , and Florence Le Calvez-KelmFlorence Le Calvez-Kelm More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003247.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Detecting pre-clinical urothelial carcinoma (UC) using urinary comprehensive genomic profiling (uCGP) may provide a valuable opportunity for early detection and screening of high-risk populations. The UroAmp (Convergent Genomics) uCGP test uses DNA sequencing to identify mutations across 60 genes. We study a subset of these genes, considering 10 genes with the highest performance, testing the potential of a screening modified uCGP (muCGP) to detect preclinical UC. METHODS: A UC screening model was developed using muCGP data from a training cohort consisting of 140 urology controls & 96 tumors (56 de novo, 40 recurrent). Model validation was performed in two studies: first a multi-institutional case-control design with 96 controls & 70 UC cases (22 de novo, 48 surveillance); a second using a nested case-control design within the prospective Golestan Cohort Study (50,045 participants). The nested cohort consisted of 29 asymptomatic individuals who subsequently developed primary UC (median time to UC 7.3 yrs) and 98 matched controls (median f/u 6.1 yrs). RESULTS: The UC screening model was trained to a sensitivity of 88% (97% sensitivity for HG) and specificity of 94%. In the first validation, a sensitivity of 86% in de novo (87% for HG), 71% overall (de novo + recurrent tumors), and specificity 94% was observed. In the Golestan cohort, baseline muCGP had a prediction sensitivity of 66% (71% for HG) and specificity 94% was observed (Figure 1A). In contrast baseline TERT predicted 48% percent of cancers with a specificity of 100%. Cancer-free survival was significantly worse in muGCP-predicted positives vs. muGCP-predicted negatives (HR 8.5, 95% CI 3.8 – 18.4, p<0.0001). When limited to UC diagnosis within five years, UroAmp detected pre-clinical UC in 90% of future cancers (Figure 1B), compared to a sensitivity of 57% using TERT mutations alone. CONCLUSIONS: Our results provide the first evidence from a population-based prospective cohort study of pre-clinical UC detection with muCGP. muCGP identifies 9 of 10 cancers that occur within the first 5 years while detecting 10 of 19 cancers that occur beyond 5 years. Further studies will determine the frequency of muCGP screening required to maximize cancer detection and refine clinical interventions to save lives. Source of Funding: Convergent Genomics with a grant from the National Cancer Institute Small Business Innovation Research Program, 5R44CA200174-05 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e304 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yair Lotan More articles by this author Keyan Salari More articles by this author Adam Feldman More articles by this author Debasish Sundi More articles by this author Jason J Lee More articles by this author Gabrielle DiFiore More articles by this author Hossein Poustchi More articles by this author Masoud Khoshnia More articles by this author Gholamreza Roshandel More articles by this author Arash Etemadi More articles by this author Mahdi Goudarzi More articles by this author Peter S. Lentz More articles by this author Kevin G. Phillips More articles by this author Vincent T. Bicocca More articles by this author Theresa M. Koppie More articles by this author Joe W. Gray More articles by this author Trevor Levin More articles by this author Reza Malekzadeh More articles by this author Mahdi Sheikh More articles by this author Florence Le Calvez-Kelm More articles by this author Expand All Advertisement PDF downloadLoading ...

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.

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

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