Mineral Intake and Cardiovascular Disease, Cancer, and All-Cause Mortality: Findings from the Golestan Cohort Study.

Associations between mineral intake and mortality in non-Western countries have not been studied adequately. This study evaluated these associations in the Golestan Cohort Study, featuring a Middle Eastern population. The mineral intake was estimated from the baseline food frequency questionnaire, adjusted by using the nutrient density method, and divided into quintiles. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the mortality. We analyzed 41,863 subjects with a mean age of 51.46 ± 8.73 years at the baseline. During 578,694 person-years of follow-up (median: 14.1 Years), 7217 deaths were recorded. Dietary calcium intake was inversely associated with the all-cause mortality (HRQ5 vs. Q1 = 0.91, 95%CI = 0.85-0.99). We observed significant associations between calcium (HRQ5 vs. Q1 = 0.82, 95% CI = 0.73-0.93), copper (HRQ5 vs. Q1 = 1.11, 95% CI = 0.99-1.26), and selenium intake (HRQ5 vs. Q1 = 1.14, 95% CI = 1.01-1.29) and CVD mortality. Dietary phosphorus (HRQ5 vs. Q1 = 0.81, 95%CI = 0.69-0.96) and copper intake (HRQ5 vs. Q1 = 0.84, 95%CI = 0.71-0.99) were inversely associated with cancer mortality. In this study within a Middle Eastern population, a higher dietary intake of calcium exhibited an inverse association with all-cause mortality. Furthermore, nuanced associations were observed in the cause-specific mortality, suggesting potential avenues for dietary interventions and emphasizing the importance of considering dietary factors in public health strategies.

Lung Cancer Risk Prediction Models for Asian Ever-Smokers.

INTRODUCTION: Although lung cancer prediction models are widely used to support risk-based screening, their performance outside Western populations remains uncertain. This study aims to evaluate the performance of 11 existing risk prediction models in multiple Asian populations and to refit prediction models for Asians. METHODS: In a pooled analysis of 186,458 Asian ever-smokers from 19 prospective cohorts, we assessed calibration (expected-to-observed ratio) and discrimination (area under the receiver operating characteristic curve [AUC]) for each model. In addition, we developed the "Shanghai models" to better refine risk models for Asians on the basis of two well-characterized population-based prospective cohorts and externally validated them in other Asian cohorts. RESULTS: Among the 11 models, the Lung Cancer Death Risk Assessment Tool yielded the highest AUC (AUC [95% confidence interval (CI)] = 0.71 [0.67-0.74] for lung cancer death and 0.69 [0.67-0.72] for lung cancer incidence) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model had good calibration overall (expected-to-observed ratio [95% CI] = 1.06 [0.90-1.25]). Nevertheless, these models substantially underestimated lung cancer risk among Asians who reported less than 10 smoking pack-years or stopped smoking more than or equal to 20 years ago. The Shanghai models were found to have marginal improvement overall in discrimination (AUC [95% CI] = 0.72 [0.69-0.74] for lung cancer death and 0.70 [0.67-0.72] for lung cancer incidence) but consistently outperformed the selected Western models among low-intensity smokers and long-term quitters. CONCLUSIONS: The Shanghai models had comparable performance overall to the best existing models, but they improved much in predicting the lung cancer risk of low-intensity smokers and long-term quitters in Asia.

Age at diagnosis for lung, colon, breast and prostate cancers: An international comparative study.

Differences in the average age at cancer diagnosis are observed across countries. We therefore aimed to assess international variation in the median age at diagnosis of common cancers worldwide, after adjusting for differences in population age structure. We used IARC's Cancer Incidence in Five Continents (CI5) Volume XI database, comprising cancer diagnoses between 2008 and 2012 from population-based cancer registries in 65 countries. We calculated crude median ages at diagnosis for lung, colon, breast and prostate cancers in each country, then adjusted for population age differences using indirect standardization. We showed that median ages at diagnosis changed by up to 10 years after standardization, typically increasing in low- and middle-income countries (LMICs) and decreasing in high-income countries (HICs), given relatively younger and older populations, respectively. After standardization, the range of ages at diagnosis was 12 years for lung cancer (median age 61-Bulgaria vs 73-Bahrain), 12 years for colon cancer (60-the Islamic Republic of Iran vs 72-Peru), 10 years for female breast cancer (49-Algeria, the Islamic Republic of Iran, Republic of Korea vs 59-USA and others) and 10 years for prostate cancer (65-USA, Lithuania vs 75-Philippines). Compared to HICs, populations in LMICs were diagnosed with colon cancer at younger ages but with prostate cancer at older ages (both pLMICS-vs-HICs < 0.001). In countries with higher smoking prevalence, lung cancers were diagnosed at younger ages in both women and men (both pcorr < 0.001). Female breast cancer tended to be diagnosed at younger ages in East Asia, the Middle East and Africa. Our findings suggest that the differences in median ages at cancer diagnosis worldwide likely reflect population-level variation in risk factors and cancer control measures, including screening.

Incident cancers attributable to using opium and smoking cigarettes in the Golestan cohort study.

Background: Opium consumption has recently been identified as a carcinogen, but the impact of opium use on cancer burden is unknown. We aimed to evaluate the fraction of cancers that could be attributed to opium use alone and in combination with cigarette smoking in a region where opium is widely used. Methods: 50,045 Iranian adults were recruited to this prospective cohort study between 2004 and 2008 and were followed through January 2022. We assessed the association between using opium and/or cigarette smoking and various cancers using proportional hazards regression models. We then calculated population attributable fractions (PAFs) for all cancers and for groups of cancers causally linked to opium and cigarette smoking. Findings: Of the total participants, 8% only used opium, 8.3% only smoked cigarettes, and 9% used both substances. During a median 14 years of follow-up, 2195 individuals were diagnosed with cancer, including 215 opium-related cancers (lung, larynx, and bladder) and 1609 tobacco-related cancers (20 types). Opium use alone was estimated to cause 35% (95% CI: 26%-45%) of opium-related cancers, while smoking cigarettes alone was estimated to cause 9% (6%-12%) of tobacco-related cancers in this population. Using opium and/or cigarettes was estimated to cause 13% (9%-16%) of all cancers, 58% (49%-66%) of opium-related cancers, and 15% (11%-18%) of tobacco-related cancers. Moreover, joint exposure to opium and cigarettes had the greatest impact on cancers of the larynx, pharynx, lung, and bladder, with PAFs ranging from 50% to 77%. Interpretation: Using opium and smoking cigarettes account for a large proportion of cancers in this population. To reduce the cancer burden, prevention policies should aim to decrease the use of both substances through public awareness campaigns and interventional efforts. Funding: The Golestan Cohort Study work was funded by the Tehran University of Medical Sciences, Cancer Research UK, U.S. National Cancer Institute, International Agency for Research on Cancer. The presented analysis was supported by the International HundredK+ Cohorts Consortium (IHCC).

Population attributable proportion and number of cancer cases attributed to potentially modifiable risk factors in Iran in 2020.

In the current study, we aimed to calculate the fraction of cancer attributable to modifiable risk factors in Iran in 2020. Population attributable fractions (PAFs) were calculated for established cancer risk factors using three data sources: the national cancer incidence reports, relative risks extracted from global and national meta-analyses, and exposure prevalence from national/subnational population-based surveys. In addition to overall cancers, the PAFs were estimated separately for each cancer site among men and women. Overall, 32.6% of cancers in 2020 in Iran were attributable to known risk factors. The PAF in men (40.2%) was twice as high as in women (21.1%). Cigarette smoking (15.4%), being overweight (5.0%), opium use (3.9%) and H. pylori infection (3.8%) were the leading causes of cancers. For men, the highest PAFs belonged to cigarette smoking (26.3%), opium use (6.8%) and being overweight (3.1%), while for women, the highest PAFs belonged to being overweight (7.2%), H. pylori infection (2.7%) and cigarette smoking (2.7%). Among Iranian men and women, the PAFs of waterpipe smoking were 2% and 0.9%, respectively. A third of incident cancers in Iran are due to modifiable exposures, mainly cigarette smoking, being overweight, and H. pylori infection. Opium consumption and waterpipe smoking collectively accounted for 8.8% of cancer occurrence in men and 1.3% in women in Iran. These emerging risk factors should be taken into consideration in future PAF studies.

Towards a sustainable transformation of municipal wastewater treatment plants into biofactories using advanced NH3-N recovery technologies: A review.

Ammonia (NH3), as a prevalent pollutant in municipal wastewater discharges, can impair aquatic life and have a negatively impact on the environment. Proper wastewater treatment and management practices are essential to protect ecosystems and keep human populations healthy. Therefore, using highly effective NH3-N recovery technologies at wastewater treatment plants (WWTPs) is widely acknowledged as a necessity. In order to improve the overall efficiency of NH3 removal/recovery processes, innovative technologies have been generally applied to reduce its concentration when discharged into natural water bodies. This study reviews the current status of the main issues affecting NH3 recovery from municipal/domestic wastewater discharges. The current study investigated the ability to recover valuable resources, e.g., nutrients, regenerated water, and energy in the form of biogas through advanced and innovative methods in tertiary treatment to achieve higher efficiency towards sustainable wastewater and resource recovery facilities (W&RRFs). In addition, the concept of paradigm shifts from WWTP to a large/full scale W&RRF has been studied with several examples of conversion to innovative bio-factories producing materials. On the other hand, the carbon footprint and the high-energy consumption of the WWTPs were also considered to assess the sustainability of these facilities.

Enhancing CO2 separation from N2 mixtures using hydrophobic porous supports immobilized with tributyl-tetradecyl-phosphonium chloride [P44414][Cl].

The main obstacles in adopting solvent-based CO2 capture technology from power plant flue gases at the industrial scale are the energy requirements for solvent regeneration and their toxicity. These challenges can be overcome using new green and more stable ionic liquids (ILs) as solvents for post-combustion CO2 capture. In the current study, tributyl-tetradecyl-phosphonium chloride [P44414][Cl] as an IL, was immobilized on hydrophobic porous supports of polypropylene (PP), polyvinylidene fluoride (PVDF), and polytetrafluoroethylene (PTFE) at 298 ± 3 K and pressures up to 2 bar. The surface morphology indicated homogenous immobilization of the IL on the membrane support. Supported ionic liquid membranes (SILMs) were tested for CO2 permeability and CO2/N2 selectivity. None of the SILMs exhibited IL leaching up to 2 bar. The PTFE-based SILM performed better than other supports with minimum loss in water contact angle (WCA) and achieved good antiwetting with a maximum CO2 permeability and selectivity over N2 of 2300 ± 139 Barrer and 31.60 ± 2.4, respectively. This work achieves CO2 permeability about two-fold more than other works having CO2/N2 selectivity range of 25-35 in similar SILMs. The diffusivity of CO2 and N2 in [P44414][Cl] was measured as 3.64 ± 0.18 and 2.01 ± 0.09 [10-8 cm2 s-1] and CO2 and N2 solubility values were 9.79 ± 0.47 and 0.19 ± 0.001 [10-2 cm3(STP) cm-3 cmHg-1], respectively. The high values of Young's modulus and tensile strength of the PTFE support-based SILM (234 ± 12 MPa and 6.07 ± 0.31 MPa, respectively) indicated the long-term application of SILM in flue gas separation. The results indicated phosphonium chloride-based ILs could be better solvent candidates for CO2 removal from large volumes of flue gases than amine-based ILs.

Simplex Droplet Digital PCR Assays for the Detection of TERT Promoter Mutations in Urine Samples for the Non-invasive Diagnosis of Urothelial Cancer.

Somatic mutations in the telomerase reverse transcriptase (TERT) promoter region are highly frequent in urothelial cancer (UC), and their detection in urine (cell-free DNA from the urine supernatant or DNA from exfoliated cells in the urine pellet) has demonstrated promising evidence as putative non-invasive biomarkers for UC detection and monitoring. However, detecting these tumour-derived mutations in urine requires highly sensitive methods, capable of measuring low-allelic fraction mutations. We developed sensitive droplet digital PCR (ddPCR) assays for detecting urinary TERT promoter mutations (uTERTpm), targeting the two most common mutations (C228T and C250T), as well as the rare A161C, C228A, and CC242-243TT mutations. Here, we described the step-by-step protocol uTERTpm mutation screening using simplex ddPCR assays and give some recommendations for isolation of DNA from urine samples. We also provide limits of detection for the two most frequent mutations and discuss advantages of the method for clinical implementation of the assays for the detection and monitoring of UC.

Regional disparities in cancer survival in Iran: Insight from a National Surveillance of Cancer Survival in Iran (IRANCANSURV).

BACKGROUND AND OBJECTIVES: We aimed to investigate geographical disparity in cancer survival in 9 provincial population-based cancer registries in Iran from 2015 to 2016. MATERIAL AND METHOD: In the current study, data from 90,862 adult patients (aged >15 years) diagnosed with cancer were retrieved from 9 population-based cancer registries across Iran. Five-year survival rates were estimated by applying relative survival approaches. We also applied the international cancer survival standard weights for age standardization. Finally, we calculated the excess hazard ratio (EHR) for each province adjusted for age, sex, and cancer sites to estimate the excess hazard ratio of mortality compared to the capital province (Tehran). RESULTS: The largest gap in survival was observed in more curable cancer types, including melanoma (41.4%), ovary (32.3%), cervix (35.0%), prostate (26.7%), and rectum (21.4%), while the observed geographical disparity in lethal cancers such as lung, brain, stomach, and pancreas was less than 15%. Compared to Tehran, we found the highest excess hazard of death in Western Azerbaijan (EHR=1.60, 95% CI 1.51, 1.65), Kermanshah (EHR=1.52, 95% CI=1.44, 1.61), and Kerman (EHR=1.46, 95% CI=1.38, 1.53). The hazard ratio of death was almost identical in Isfahan (EHR=1.04, 95% CI=1.03, 1.06) and Tehran provinces. CONCLUSION: Provinces with higher HDI had better survival rates. IRANCANSURV study showed regional disparities in cancer survival in Iran. Cancer patients in provinces with a higher Human Development Index (HDI) had a higher survival rate and lived longer compared to the patients in provinces with medium and low HDI regions.

Evaluation of pre-diagnostic blood protein measurements for predicting survival after lung cancer diagnosis.

BACKGROUND: To evaluate whether circulating proteins are associated with survival after lung cancer diagnosis, and whether they can improve prediction of prognosis. METHODS: We measured up to 1159 proteins in blood samples from 708 participants in 6 cohorts. Samples were collected within 3 years prior to lung cancer diagnosis. We used Cox proportional hazards models to identify proteins associated with overall mortality after lung cancer diagnosis. To evaluate model performance, we used a round-robin approach in which models were fit in 5 cohorts and evaluated in the 6th cohort. Specifically, we fit a model including 5 proteins and clinical parameters and compared its performance with clinical parameters only. FINDINGS: There were 86 proteins nominally associated with mortality (p < 0.05), but only CDCP1 remained statistically significant after accounting for multiple testing (hazard ratio per standard deviation: 1.19, 95% CI: 1.10-1.30, unadjusted p = 0.00004). The external C-index for the protein-based model was 0.63 (95% CI: 0.61-0.66), compared with 0.62 (95% CI: 0.59-0.64) for the model with clinical parameters only. Inclusion of proteins did not provide a statistically significant improvement in discrimination (C-index difference: 0.015, 95% CI: -0.003 to 0.035). INTERPRETATION: Blood proteins measured within 3 years prior to lung cancer diagnosis were not strongly associated with lung cancer survival, nor did they importantly improve prediction of prognosis beyond clinical information. FUNDING: No explicit funding for this study. Authors and data collection supported by the US National Cancer Institute (U19CA203654), INCA (France, 2019-1-TABAC-01), Cancer Research Foundation of Northern Sweden (AMP19-962), and Swedish Department of Health Ministry.

Smoking Cessation After Diagnosis of Kidney Cancer Is Associated With Reduced Risk of Mortality and Cancer Progression: A Prospective Cohort Study.

PURPOSE: To investigate whether postdiagnosis smoking cessation may affect the risk of death and disease progression in patients with renal cell carcinoma (RCC) who smoked at the time of diagnosis. METHODS: Two hundred twelve patients with primary RCC were recruited between 2007 and 2016 from the Urological Department in N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia. Upon enrollment, a structured questionnaire was completed, and the patients were followed annually through 2020 to repeatedly assess their smoking status and disease progression. Survival probabilities and hazards for all-cause and cancer-specific mortality and disease progression were investigated using extended the Kaplan-Meier method, time-dependent Cox proportional hazards regression, and Fine-Gray competing-risk models. RESULTS: Patients were followed for a median of 8.2 years. During this time, 110 cases of disease progression, 100 total deaths, and 77 cancer-specific deaths were recorded. Eighty-four patients (40%) quit smoking after diagnosis. The total person-years at risk for this analysis were 748.2 for continuing smoking and 611.2 for quitting smoking periods. At 5 years of follow-up, both overall survival (85% v 61%) and progression-free survival (80% v 57%) rates were higher during the quitting than continuing smoking periods (both P < .001). In the multivariable time-dependent models, quitting smoking was associated with lower risk of all-cause mortality (hazard ratio [HR], 0.51; 95% CI, 0.31 to 0.85), disease progression (HR, 0.45; 95% CI, 0.29 to 0.71), and cancer-specific mortality (HR, 0.54; 95% CI, 0.31 to 0.93). The beneficial effect of quitting smoking was evident across all subgroups, including light smokers versus moderate-heavy smokers and those with early-stage versus late-stage tumors. CONCLUSION: Quitting smoking after RCC diagnosis may significantly improve survival and reduce the risk of disease progression and cancer mortality among patients who smoke.

Survival and prognostic factors of early-stage non-small cell lung cancer in Central and Eastern Europe: A prospective cohort study.

BACKGROUND: Although early diagnosis and surgical resection of the tumor have been shown to be the most important predictors of lung cancer survival, long-term survival for surgically-resected early-stage lung cancer remains poor. AIMS: In this prospective study we aimed to investigate the survival and prognostic factors of surgically-resected early-stage non-small cell lung cancer (NSCLC) in Central and Eastern Europe. METHODS: We recruited 2052 patients with stage I-IIIA NSCLC from 9 centers in Russia, Poland, Serbia, Czech Republic, and Romania, between 2007-2016 and followed them annually through 2020. RESULTS: During follow-up, there were 1121 deaths (including 730 cancer-specific deaths). Median survival time was 4.9 years, and the 5-year overall survival was 49.5%. In the multivariable model, mortality was increased among older individuals (HR for each 10-year increase: 1.31 [95% CI: 1.21-1.42]), males (HR:1.24 [1.04-1.49]), participants with significant weight loss (HR:1.25 [1.03-1.52]), current smokers (HR:1.30 [1.04-1.62]), alcohol drinkers (HR:1.22 [1.03-1.44]), and those with higher stage tumors (HR stage IIIA vs. I: 5.54 [4.10 - 7.48]). However, education, chronic obstructive pulmonary diseases (COPD), and tumor histology were not associated with risk of death. All baseline indicators of smoking and alcohol drinking showed a dose-dependent association with the risk of cancer-specific mortality. This included pack-years of cigarettes smoked (p-trend = 0.04), quantity of smoking (p-trend = 0.008), years of smoking (p-trend = 0.010), gram-days of alcohol drank (p-trend = 0.002), frequency of drinking (p-trend = 0.006), and years of drinking (p-trend = 0.016). CONCLUSION: This study shows that the 5-year survival rate of surgically-resected stage I-IIIA NSCLC is still around 50% in Central and Eastern Europe. In addition to non-modifiable prognostic factors, lifetime patterns of smoking and alcohol drinking affected the risk of death and disease progression in a dose-dependent manner in this population.

The carcinogenicity of opium consumption: a systematic review and meta-analysis.

The carcinogenicity of opium consumption was recently evaluated by a Working Group convened by the International Agency for Research on Cancer (IARC). We supplement the recent IARC evaluation by conducting an extended systematic review as well as a quantitative meta-analytic assessment of the role of opium consumption and risk for selected cancers, evaluating in detail various aspects of study quality on meta-analytic findings. We searched the published literature to identify all relevant studies on opium consumption and risk of selected cancers in humans through 31 October, 2022. Meta-relative risks (mRRs) and associated 95% confidence intervals (CIs) were estimated using random-effects models for studies of cancer of the urinary bladder, larynx, lung, oesophagus, pancreas, and stomach. Heterogeneity among studies was assessed using the I2 statistic. We assessed study quality and conducted sensitivity analyses to evaluate the impact of potential reverse causation, protopathic bias, selection bias, information bias, and confounding. In total, 2 prospective cohort studies and 33 case-control studies were included. The overall pooled mRR estimated for 'ever or regular' versus 'never' use of opium ranged from 1.50 (95% CI 1.13-1.99, I2 = 0%, 6 studies) for oesophageal cancer to 7.97 (95% CI 4.79-13.3, I2 = 62%, 7 studies) for laryngeal cancer. Analyses of cumulative opium exposure suggested greater risk of cancer associated with higher opium consumption. Findings were robust in sensitivity analyses excluding studies prone to potential methodological sources of biases and confounding. Findings support an adverse association between opium consumption and cancers of the urinary bladder, larynx, lung, oesophagus, pancreas and stomach.

Current Status and Future Prospects for Esophageal Cancer.

Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two main histological subtypes with distinct epidemiological and clinical features. While the global incidence of ESCC is declining, the incidence of EAC is increasing in many countries. Decades of epidemiologic research have identified distinct environmental exposures for ESCC and EAC subtypes. Recent advances in understanding the genomic aspects of EC have advanced our understanding of EC causes and led to using specific genomic alterations in EC tumors as biomarkers for early diagnosis, treatment, and prognosis of this cancer. Nevertheless, the prognosis of EC is still poor, with a five-year survival rate of less than 20%. Currently, there are significant challenges for early detection and secondary prevention for both ESCC and EAC subtypes, but Cytosponge™ is shifting this position for EAC. Primary prevention remains the preferred strategy for reducing the global burden of EC. In this review, we will summarize recent advances, current status, and future prospects of the studies related to epidemiology, time trends, environmental risk factors, prevention, early diagnosis, and treatment for both EC subtypes.

Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program.

The Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program is an NCI-funded initiative with an objective to develop tools to optimize low-dose CT (LDCT) lung cancer screening. Here, we describe the rationale and design for the Risk Biomarker and Nodule Malignancy projects within INTEGRAL. The overarching goal of these projects is to systematically investigate circulating protein markers to include on a panel for use (i) pre-LDCT, to identify people likely to benefit from screening, and (ii) post-LDCT, to differentiate benign versus malignant nodules. To identify informative proteins, the Risk Biomarker project measured 1161 proteins in a nested-case control study within 2 prospective cohorts (n = 252 lung cancer cases and 252 controls) and replicated associations for a subset of proteins in 4 cohorts (n = 479 cases and 479 controls). Eligible participants had a current or former history of smoking and cases were diagnosed up to 3 years following blood draw. The Nodule Malignancy project measured 1078 proteins among participants with a heavy smoking history within four LDCT screening studies (n = 425 cases diagnosed up to 5 years following blood draw, 430 benign-nodule controls, and 398 nodule-free controls). The INTEGRAL panel will enable absolute quantification of 21 proteins. We will evaluate its performance in the Risk Biomarker project using a case-cohort study including 14 cohorts (n = 1696 cases and 2926 subcohort representatives), and in the Nodule Malignancy project within five LDCT screening studies (n = 675 cases, 680 benign-nodule controls, and 648 nodule-free controls). Future progress to advance lung cancer early detection biomarkers will require carefully designed validation, translational, and comparative studies.

Population-based investigation of common and deviating patterns of gastric cancer and oesophageal cancer incidence across populations and time.

BACKGROUND: The subtypes of gastric cancer (GC) and oesophageal cancer (EC) manifest distinct epidemiological profiles. Here, we aim to examine correlations in their incidence rates and to compare their temporal changes globally, both overall and by subtype. METHODS: Long-term incidence data were obtained from population-based registries available from the Cancer Incidence in Five Continents series. Variation in the occurrence of EC and GC (overall and by subtype) was assessed using the GC:EC ratio of sex-specific age-standardised rates (ASR) in 2008-2012. Average annual per cent changes were estimated to assess temporal trends during 1998-2012. RESULTS: ASRs for GC and EC varied remarkably across and within world regions. In the countries evaluated, the GC:EC ratio in men exceeded 10 in several South American countries, Algeria and Republic of Korea, while EC dominated in most sub-Saharan African countries. High rates of both cardia gastric cancer and oesophageal squamous cell carcinoma (ESCC) were observed in several Asian populations. Non-cardia gastric cancer rates correlated positively with ESCC rates (r=0.60) and negatively with EAC (r=-0.79). For the time trends, while GC incidence has been uniformly decreasing by on average 2%-3% annually over 1998-2012 in most countries, trends for EC depend strongly on histology, with several but not all countries experiencing increases in EAC and decreases in ESCC. CONCLUSIONS: Correlations between GC and EC incidence rates across populations are positive or inverse depending on the GC subsite and EC subtype. Multisite studies that include a combination of populations whose incidence rates follow and deviate from these patterns may be aetiologically informative.

National and Regional Fraction of Cancer Incidence and Death Attributable to Current Tobacco and Water-Pipe Smoking in the Eastern Mediterranean Countries in 2020.

INTRODUCTION: We aimed to calculate the Population Attributable Fraction (PAF) of cancers due to tobacco use in the Eastern Mediterranean Region (EMRO), where water-pipe smoking is prevalent but its effect was not considered in previous studies. AIMS AND METHODS: We applied Levin's formula to estimate PAFs of cancers due to tobacco use (defined as all type tobacco including both cigarette and water-pipe). We also calculated PAF of water-pipe smoking separately. Exposure prevalence data were retrieved from representative national and subnational surveys. Data on cancer incidence and death were also and cancer cases were obtained GLOBOCAN 2020. We also obtained associated relative risks from published meta-analyses. RESULTS: Of the total 715 658 incident adult cancer cases that were reported in 2020 in EMRO, 14.6% (n = 104 800) was attributable to tobacco smoking (26.9% [n = 92 753]) in men versus 3.3% (n = 12 048) in women. Further, 1.0% of incident adult cancers were attributable to current water-pipe use (n = 6825) (1.7% [n = 5568]) in men versus 0.4% (n = 1257 in women). CONCLUSIONS: PAFs of cancers due to tobacco smoking in EMRO were higher in our study than previous reports. This could be due to the neglected role of water-pipe in previous studies that is a common tobacco smoking method in EMRO. The proportion of cancers attributable to water-pipe smoking in EMRO might be underestimated due to lack of research on the risk of cancers associated with water-pipe smoking and also less developed cancer registries in EMRO. IMPLICATIONS: In this study, we found higher PAFs for cancers due to tobacco smoking in the Eastern Mediterranean (EMR) region than previous reports. This difference could be due to ignoring the role of water-pipe smoking in previous studies. In 2020, 1% of incident cancers and 1.3% of cancer-related deaths in EMRO were attributable to water-pipe smoking. We also found a big difference in PAFs of cancers due to tobacco and water-pipe smoking across EMRO countries, with Tunisia, Lebanon, and Jordan having the highest, and Djibouti, Sudan, and Somalia having the lowest proportions of cancers attributable to tobacco and water-pipe smoking.

Diet Quality and Subsequent Incidence of Upper Gastrointestinal Cancers: Results from the Golestan Cohort Study.

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 50045 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.

TERT Promoter Mutations as Simple and Non-Invasive Urinary Biomarkers for the Detection of Urothelial Bladder Cancer in a High-Risk Region.

Bladder cancer (BC) is the 10th most common cancer in the world. While there are FDA-approved urinary assays to detect BC, none have demonstrated sufficient sensitivity and specificity to be integrated into clinical practice. Telomerase Reverse Transcriptase (TERT) gene mutations have been identified as the most common BC mutations that could potentially be used as non-invasive urinary biomarkers to detect BC. This study aims to evaluate the validity of these tests to detect BC in the Kerman province of Iran, where BC is the most common cancer in men. Urine samples of 31 patients with primary (n = 11) or recurrent (n = 20) bladder tumor and 50 controls were prospectively collected. Total urinary DNA was screened for the TERT promoter mutations (uTERTpm) by Droplet Digital PCR (ddPCR) assays. The performance characteristics of uTERTpm and the influence by disease stage and grade were compared to urine cytology results. The uTERTpm was 100% sensitive and 88% specific to detect primary BC, while it was 50% sensitive and 88% specific in detecting recurrent BC. The overall sensitivity and specificity of uTERTpm to detect bladder cancer were 67.7% and 88.0%, respectively, which were consistent across different tumor stages and grades. The most frequent uTERTpm mutations among BC cases were C228T (18/31), C250T (4/31), and C158A (1/31) with mutant allelic frequency (MAF) ranging from 0.2% to 63.3%. Urine cytology demonstrated a similar sensitivity (67.7%), but lower specificity (62.0%) than uTERTpm in detecting BC. Combined uTERTpm and urine cytology increased the sensitivity to 83.8%, but decreased the specificity to 52.0%. Our study demonstrated promising diagnostic accuracy for the uTERTpm as a non-invasive urinary biomarker to detect, in particular, primary BC in this population.