Body Mass Index and Risk of Colorectal Cancer Incidence and Mortality in Asia.

Importance: The global burden of obesity is increasing, as are colorectal cancer (CRC) incidence and mortality. Objectives: To assess the association between body mass index (BMI) and risks of incident CRC and CRC-related death in the Asian population. Design, Setting, and Participants: This cohort study includes data pooled from 17 prospective cohort studies included in The Asia Cohort Consortium. Cohort enrollment was conducted from January 1, 1984, to December 31, 2002. Median follow-up time was 15.2 years (IQR, 12.1-19.2 years). Data were analyzed from January 15, 2023, through January 15, 2024. Exposure: Body mass index, calculated as weight in kilograms divided by height in meters squared. Main Outcomes and Measures: The primary outcomes were CRC incidence and CRC-related mortality. The risk of events is reported as adjusted hazard ratios (AHRs) and 95% CIs for incident CRC and death from CRC using the Cox proportional hazards regression model. Results: To assess the risk of incident CRC, 619 981 participants (mean [SD] age, 53.8 [10.1] years; 52.0% female; 11 900 diagnosed incident CRC cases) were included in the study, and to assess CRC-related mortality, 650 195 participants (mean [SD] age, 53.5 [10.2] years; 51.9% female; 4550 identified CRC deaths) were included in the study. A positive association between BMI and risk of CRC was observed among participants with a BMI greater than 25.0 to 27.5 (AHR, 1.09 [95% CI, 1.03-1.16]), greater than 27.5 to 30.0 (AHR, 1.19 [95% CI, 1.11-1.29]), and greater than 30.0 (AHR, 1.32 [95% CI, 1.19-1.46]) compared with those with a BMI greater than 23.0 to 25.0 (P < .001 for trend), and BMI was associated with a greater increase in risk for colon cancer than for rectal cancer. A similar association between BMI and CRC-related death risk was observed among participants with a BMI greater than 27.5 (BMI >27.5-30.0: AHR, 1.18 [95% CI, 1.04-1.34]; BMI >30.0: AHR, 1.38 [95% CI, 1.18-1.62]; P < .001 for trend) and was present among men with a BMI greater than 30.0 (AHR, 1.87 [95% CI, 1.49-2.34]; P < .001 for trend) but not among women (P = .15 for trend) (P = .02 for heterogeneity). Conclusions and Relevance: In this cohort study that included a pooled analysis of 17 cohort studies comprising participants across Asia, a positive association between BMI and CRC incidence and related mortality was found. The risk was greater among men and participants with colon cancer. These findings may have implications to better understand the burden of obesity on CRC incidence and related deaths in the Asian population.

Volatile organic compounds and mortality from ischemic heart disease: A case-cohort study.

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 high-performance 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.

Incidence and risk factors of pancreatic cancer during 15 years follow-up in the Golestan Cohort Study in Iran.

BACKGROUND: Cancer is one of the main causes of death in the worldwide. Pancreatic Cancer (PC) is prevalent in developed and increasing in developing countries. PC is important because of its low survival rate, high fatality, and increasing incidence. Therefore, identifying risk factors to prevent its development is necessary. This study aimed to determine incidence of PC and its risk factors in the Golestan Cohort Study (GCS) in Iran. METHOD: This study is a prospective population-based cohort study in the frame of GCS with 15 years of follow-up for PC. GCS was launched in the Golestan province of Iran with 50045 participants who were 40 to 75 years old. variables included: age, gender, education status, smoking, alcohol consumption, opium usage, type of blood group, dyslipidemia, body mass index (BMI), waist circumference (WC), family history (FH) of PC, ethnicity, and history of diabetes mellitus (DM). RESULT: Among 50045 participants of GCS during 15 years of follow up, 100 people were diagnosed PC. PC incidence was 0.2%. Age-standardized incidence rate (ASR) of PC in the study population was 11.12 per 100,000 person-years. People with age ≥60 years were 46, in 50-59 years old group were 36, and 18 of them were <50 years (p<0.001). The smoking rate in PC group was 27% (p<0.01). Univariate model of cox regression analysis showed age 50-59, ≥60 years compared to <50 years [HR:3.006, 95%CI (1.707-5.294), p<0.001], [HR: 6.727, 95% CI (3.899-11.608), p<0.001], male gender [HR:1.541, 95%CI (1.041-2.281), p = 0.031], opium use [HR:1.436, 95% CI (0.887-2.324), p = 0.141], and smoking [HR:1.884, 95%CI (1.211-2.929), p = 0.005] were predictors for PC. In the multivariate model after adjusting, age 50-59 [HR:2.99, 95% CI (1.698-5.265), p<0.001], and ≥60 years [HR: 6.564, 95% CI (3.797-11.346), p<0.001] was the only predictor for PC. CONCLUSION: This study revealed an incidence of PC 0.2% in GCS in Iran. Main risk factor for PC was older age.

Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium.

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust.

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.

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

BACKGROUND: Poor oral health has been linked to various systemic diseases, including multiple cancer types, but studies of its association with lung cancer have been inconclusive. METHODS: We examined the relationship between dental status and lung cancer incidence and mortality in the Golestan Cohort Study, a large, prospective cohort of 50,045 adults in northeastern Iran. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between three dental health measures (i.e., number of missing teeth; the sum of decayed, missing, or filled teeth (DMFT); and toothbrushing frequency) and lung cancer incidence or mortality with adjustment for multiple potential confounders, including cigarette smoking and opium use. We created tertiles of the number of lost teeth/DMFT score in excess of the loess adjusted, age- and sex-specific predicted numbers, with subjects with the expected number of lost teeth/DMFT or fewer as the reference group. RESULTS: During a median follow-up of 14 years, there were 119 incident lung cancer cases and 98 lung cancer deaths. Higher DMFT scores were associated with a progressively increased risk of lung cancer (linear trend, p = 0.011). Compared with individuals with the expected DMFT score or less, the HRs were 1.27 (95% CI: 0.73, 2.22), 2.15 (95% CI: 1.34, 3.43), and 1.52 (95% CI: 0.81, 2.84) for the first to the third tertiles of DMFT, respectively. The highest tertile of tooth loss also had an increased risk of lung cancer, with a HR of 1.68 (95% CI: 1.04, 2.70) compared with subjects with the expected number of lost teeth or fewer (linear trend, p = 0.043). The results were similar for lung cancer mortality and did not change substantially when the analysis was restricted to never users of cigarettes or opium. We found no associations between toothbrushing frequency and lung cancer incidence or mortality. CONCLUSION: Poor dental health indicated by tooth loss or DMFT, but not lack of toothbrushing, was associated with increased lung cancer incidence and mortality in this rural Middle Eastern population.

Exposure to polycyclic aromatic hydrocarbons, volatile organic compounds, and tobacco-specific nitrosamines and incidence of esophageal cancer.

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.

Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium.

Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2 ); normal (18.5-22.9 kg/m2 ); overweight (23-24.9 kg/m2 ); and obese (25+ kg/m2 ). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.

Higher intakes of fiber, total vegetables, and fruits may attenuate the risk of all-cause and cause-specific mortality: findings from a large prospective cohort study.

BACKGROUND: Although studies have reported an inverse association between fruits, vegetables, and fiber consumption and all-cause and cause-specific mortality, the issue remains incompletely defined in the Middle Eastern population. AIMS: The current study aimed to investigate the association between dietary fiber, fruit, and vegetable intake and all-cause and cause-specific mortality. METHODS: A total of 48632 participants (mean age = 52years), 57.5% (n = 27974) women and 42.5% (n = 20658) men, were recruited from an ongoing large-scale prospective cohort study (the Golestan Cohort Study (GCS)), in the north of Iran. Using a validated semi-quantitative 116-item food questionnaire, dietary intakes were collected. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) of all-cause and cause-specific mortality were reported. RESULTS: After approximately 14 years of follow-up, 10,774 deaths were recorded. In the fully adjusted model, compared to those in the lowest quintile of intake, those in the second and third quintiles of dietary fiber intake had a 7%-10% reduction in risk of all-cause mortality, and a 15%-17% reduction in the risk of mortality from other causes. Increasing consumption of fruits was also associated with a decreased risk of mortality for all-cause mortality by 9%-11%, and all cancer by 15-20%. Further, those in the third and fourth quintiles of vegetables intake had 11%-12% lower risk for CVD mortality. DISCUSSION: The results from the GCS further support the current recommendations on following a healthy diet containing proper amounts of fiber, vegetables, and fruits, as health-protective dietary items. CONCLUSIONS: Higher intake of dietary fiber, fruits, and vegetables has the potential to reduce both overall and cause-specific mortality rates. However, additional cohort studies with larger sample size and long-term follow-up durations are required to establish these findings.

A Single nucleotide polymorphism in the ALDH2 gene modifies the risk of esophageal squamous cell carcinoma in BRCA2 p.K3326* carriers.

Esophageal squamous cell carcinoma (ESCC) has a very high incidence rate in northeastern Iran. Our team previously reported the BReast CAncer gene 2 (BRCA2) p.K3326* mutation as a moderately penetrant ESCC susceptibility variant in northern Iran (odds ratio (OR) = 3.64, 95% confidence interval (CI) = 1.74-7.59, P = 0.0003). Recently, it has been reported that aldehydes can induce BRCA2 haploinsufficiency in cells with a heterozygous pathogenic BRCA2 mutation and predispose them to carcinogenic effects. Based on this observation, we speculate that dysfunctional variants in Aldehyde Dehydrogenase 2 Family Member (ALDH2) may result in aldehyde-induced BRCA2 haploinsufficiency and increase cancer risk in BRCA2 mutation carriers. In support of this hypothesis, our team recently reported the breast cancer risk modifying effect of an ALDH2 common polymorphism, rs10744777, among Polish carriers of the BRCA2 p.K3326* mutation. In the current case-control study, we aimed to investigate the ESCC risk modifying effect of this ALDH2 polymorphism among BRCA2 p.K3326* mutation carriers. We assessed the interaction between the ALDH2 rs10744777 polymorphism and BRCA2 p.K3326* mutation in ESCC risk by genotyping this ALDH2 variant in the germline DNA of 746 ESCC cases and 1,373 controls from northern Iran who were previously genotyped for the BRCA2 p.K3326* mutation. Among a total of 464 individuals with TT genotype of the ALDH2 rs10744777 polymorphism, which is associated with lower ALDH2 expression, we found 9 of 164 cases versus 3 of 300 controls who carried the BRCA2 p.K3326* variant (OR = 5.66, 95% CI = 1.22-26.2, P = 0.018). This finding supports our hypothesis that the ALDH2-rs10744777 TT genotype may be a significant risk modifier of ESCC in individuals with a BRCA2 p.K3326* mutation.

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).

Smoke exposure associated with higher urinary benzene biomarker muconic acid (MUCA) in Golestan Cohort Study participants.

Background. Benzene is a known human carcinogen. Human exposure to benzene can be assessed by measuring trans, trans-muconic acid (MUCA) in urine. Golestan Province in northeastern Iran has been reported to have high incidence of esophageal cancer linked to the use of tobacco products. This manuscript evaluates the urinary MUCA concentrations among the participants of the Golestan Cohort Study (GCS).Methods. We analyzed MUCA concentration in 177 GCS participants' urine samples and performed nonparametric pairwise multiple comparisons to determine statistically significant difference among six different product use groups. Mixed effects model was fitted on 22 participants who exclusively smoked cigarette and 51 participants who were classified as nonusers. The urinary MUCA data were collected at the baseline and approximately five years later, and intraclass correlation coefficient (ICC) was calculated from the model.Results. Compared with nonusers, tobacco smoking was associated with higher urinary MUCA concentrations. Based on the nonparametric test of pairwise multiple comparisons, MUCA concentrations among participants who smoked combusted tobacco products were statistically significantly higher compared to nonusers. Urinary MUCA collected five years apart from the same individuals showed moderate reliability (ICC = 0.41), which was expected given the relatively short half-life (∼6 h) of MUCA.Conclusion. Our study revealed that tobacco smoke was positively associated with increased levels of urinary MUCA concentration, indicating that it is a significant source of benzene exposure among GCS participants.

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.

Dietary Advanced Glycation End Products and Risk of Overall and Cause-Specific Mortality: Results from the Golestan Cohort Study.

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.

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.

RNA-sequencing for transcriptional profiling of whole blood in early stage and metastatic pancreatic cancer patients.

We investigated the transcriptional profile of whole blood in early and metastatic stages of pancreatic cancer (PaC) patients to identify potential diagnostic factors for early diagnosis. Blood samples from 18 participants (6 healthy individuals, 6 patients in early stage (I/II) PaC, and 6 patients in metastatic PaC) were analyzed by RNA-sequencing. The expression levels of identified genes were subsequently compared with their expression in pancreatic tumor tissues based on TCGA data reported in UALCAN and GEPIA2 databases. Overall, 331 and 724 genes were identified as differentially expressed genes in early and metastatic stages, respectively. Of these, 146 genes were shared by early and metastatic stages. Upregulation of PTCD3 and UBA52 genes and downregulation of A2M and ARID1B genes in PaC patients were observed from early stage to metastasis. TCGA database showed increasing trend in expression levels of these genes from stage I to IV in pancreatic tumor tissue. Finally, we found that low expression of PTCD3, A2M, and ARID1B genes and high expression of UBA52 gene were positively correlated with PaC patients survival. We identified a four-gene set (PTCD3, UBA52, A2M, and ARID1B) expressed in peripheral blood of early stage and metastatic PaC patients that may be useful for PaC early diagnosis.

Aspirin Use and Risk of Pancreatic Ductal Adenocarcinoma: A Large Case-Control Study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with a five-year survival rate of approximately 5%. The incidence and mortality rates of PDAC are increasing, and the results of medical treatments remain unsatisfactory. Some conflicting evidence suggests that aspirin intake may reduce the risk of PDAC. This study aimed to evaluate the association between regular low-dose aspirin use (80-mg aspirin tablets, 5-7 tablets/week) and the risk of PDAC. METHODS: This prospective, hospital-based, case-control study was performed on 470 PDAC patients (case group) and 526 sex and age-matched controls, in Tehran, Iran from 2011 to 2018. The participants were interviewed regarding the patterns of aspirin use. Data are expressed as mean±SD or frequency and percentage as appropriate. Differences in frequency between the case and control groups were evaluated based on the analysis of the contingency table (χ2 test and Fisher's exact test). Propensity score models were designed to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) for PDAC with respect to aspirin use, adjusted for age, sex, smoking status, opium use, diabetes mellitus, place of residence, and family history of cancer in first-degree relatives. RESULTS: About 60% of PDAC patients were male in this study. Also, 25.2% of PDAC patients had a family history of cancer in one of their first-degree relatives, 21.99% were smokers, 13.9% were opium users, and 11.7% had a history of diabetes. Aspirin was used by 22.77% of PDAC patients and 18.25% of the controls. Ever aspirin use (OR: 1.01, 95% CI: 0.89 - 1.14) was not associated with PDAC. CONCLUSION: Overall, aspirin use was not associated with a reduced risk of PDAC.

Iron, Copper, and Magnesium Concentration in Hair and Risk of Esophageal Cancer: A Nested Case-Control Study.

BACKGROUND: An association has already been hypothesized between iron, copper, and magnesium status assessed through food frequency questionnaires (FFQs) and the risk of esophageal squamous cell carcinoma (ESCC). However, self-reported dietary assessment methods are prone to measurement errors. We studied the association between iron, copper, and magnesium status and ESCC risk, using hair samples as a long exposure biomarker. METHODS: We designed a nested case-control study within the Golestan Cohort Study, that recruited about 50000 participants in 2004-2008, and collected biospecimens at baseline. We identified 96 incident cases of ESCC with available hair samples. They were age-matched with cancer-free controls from the cohort. We used inductively coupled plasma mass spectrometry (ICP-MS) to measure iron, copper, and magnesium concentrations in hair samples. We used multiple logistic regression models to determine odds ratios and 95% confidence intervals. RESULTS: Median concentrations of iron, copper, and magnesium were 35.4, 19.3, and 41.7 ppm in cases and 25.8, 18.3, and 50.0 ppm in controls, respectively. Iron was significantly associated with the risk of ESCC in continuous analysis (OR=1.41, 95% CI=1.03-1.92), but not in the tertiles analyses (ORT3 vs. T1=1.81, 95% CI=0.77-4.28). No associations were observed between copper and magnesium and ESCC risk, in either the tertiles models or the continuous estimate (copper: ORT3 vs. T1=2.56, 95% CI=1.00-6.54; magnesium: ORT3 vs. T1=0.75, 95% CI=0.32-1.78). CONCLUSION: Higher iron status may be related to a higher risk of ESCC in this population.

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.

The association of dietary intake and plasma fatty acid panel in pancreatic cancer patients: Results from Golestan cohort study.

BACKGROUND & AIMS: High mortality rate of pancreatic cancer (PC) as one of the most common cancers worldwide made it a center of attention for recent researches on its pathology, etiology, screening and early diagnosis. In previous researches, association of dietary intake and plasma levels of fatty acids with risk of pancreatic cancer was investigated. In this study we aimed to evaluate the correlation between dietary and plasma fatty acids in case and control groups. METHODS: From 50,045 adults between 40-75 years old participated in Golestan cohort study, fifty incident cases of PC were diagnosed and 150 controls matched by age, sex and residence place were randomly selected. Dietary intakes and plasma levels of fatty acids was evaluated by validated food-frequency questionnaire (FFQ) and Gas Chromatography - Flame Ionization Detector (GC-FID), respectively. Then, Spearman's correlation was used to measure the correlation between dietary and plasma levels of fatty acids in case and control groups. RESULTS: Among all the fatty acids, there was a significant association between plasma and dietary intake of a few fatty acids including trans fatty acids (TFA), polyunsaturated fatty acids (PUFA), 22:6n-3 and 14:0 only in control group. Only total PUFA intake modified plasma level of some fatty acids in case group. There was no difference between association of desaturase enzymes and fatty acids in case and controls. CONCLUSIONS: Since, plasma levels of fatty acids might be influenced by recent diet, we did not find any specific differences between the associations of plasma levels of fatty acids with dietary intake of fats in case and control groups.