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.

Validity and reproducibility of the PERSIAN Cohort food frequency questionnaire: assessment of major dietary patterns.

BACKGROUND: Dietary patterns, encompassing an overall view of individuals' dietary intake, are suggested as a suitable means of assessing nutrition's role in chronic disease development. The aim of this study was to evaluate the validity and reproducibility of a food frequency questionnaire (FFQ) designed for use in the Prospective Epidemiological Research Studies in IrAN (PERSIAN), by comparing major dietary patterns assessed by the FFQ with a reference method. METHODS: Study participants included men and women who enrolled in the PERSIAN Cohort Study at seven of the eighteen centers. These centers were chosen to include dietary variations observed among the different Iranian ethnic populations. Two FFQ were completed for each participant over a one-year study period (FFQ1 upon enrollment and FFQ2 at the end of the study), with 24 interviewer-administered 24-hour dietary recalls (24 h) being completed monthly in between. Spearman correlation coefficients (SCC) were used comparing FFQs 1 and 2 to the 24 h to assess validity, while FFQ1 was compared to FFQ2 to assess reproducibility of the questionnaire. RESULTS: Three major dietary patterns-Healthy, Low Protein/High Carb and Unhealthy-were identified, accounting for 70% of variance in the study population. Corrected SCC ranged from 0.31 to 0.61 in the validity and from 0.34 to 0.57 in reproducibility analyses, with the first two patterns, which accounted for over 50% of population variance, correlated at above 0.5 in both parameters, showing acceptable findings. CONCLUSIONS: The PERSIAN Cohort FFQ is suitable for identification of major dietary patterns in the populations it is used for, in order to assess diet-disease relationships.

Dietary intake of vitamin C and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Previous studies suggest that dietary vitamin C is inversely associated with gastric cancer (GC), but most of them did not consider intake of fruit and vegetables. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project, a consortium of epidemiological studies on GC. METHODS: Fourteen case-control studies were included in the analysis (5362 cases, 11,497 controls). We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the association between dietary intake of vitamin C and GC, adjusted for relevant confounders and for intake of fruit and vegetables. The dose-response relationship was evaluated using mixed-effects logistic models with second-order fractional polynomials. RESULTS: Individuals in the highest quartile of dietary vitamin C intake had reduced odds of GC compared with those in the lowest quartile (OR: 0.64; 95% CI: 0.58, 0.72). Additional adjustment for fruit and vegetables intake led to an OR of 0.85 (95% CI: 0.73, 0.98). A significant inverse association was observed for noncardia GC, as well as for both intestinal and diffuse types of the disease. The results of the dose-response analysis showed decreasing ORs of GC up to 150-200 mg/day of vitamin C (OR: 0.54; 95% CI: 0.41, 0.71), whereas ORs for higher intakes were close to 1.0. CONCLUSIONS: The findings of our pooled study suggest that vitamin C is inversely associated with GC, with a potentially beneficial effect also for intakes above the currently recommended daily intake (90 mg for men and 75 mg for women).

Effectiveness of polypill for primary and secondary prevention of cardiovascular disease: a pragmatic cluster-randomised controlled trial (PolyPars).

BACKGROUND: We aimed to investigate the effectiveness of fixed-dose combination therapy (polypill) for primary and secondary prevention of major cardiovascular diseases in a typical rural setting. METHODS: The PolyPars Study is a two-arm pragmatic cluster-randomised trial nested within the PARS cohort study, including all residents aged over 50 years in the entire district in southern Iran. The 91 villages underwent random allocation into two arms: the control arm, encompassing 45 clusters, was subjected to non-pharmacological intervention (educational training on healthy lifestyle), whereas the intervention arm, comprising 46 clusters, received the non-pharmacological interventions in conjunction with a once-daily polypill tablet. This tablet comprised two antihypertensive agents, a statin and aspirin. The primary outcome was the first occurrence of major cardiovascular events defined as a composite of hospitalisation for acute coronary syndrome (non-fatal myocardial infarction and unstable angina), fatal myocardial infarction, non-fatal and fatal stroke, sudden death and heart failure. The Cox regression model, with shared frailty, was used to account for clustering effect. RESULTS: During December 2015-December 2016, a total of 4415 participants aged 50-75 years were recruited (2200 participants in the intervention arm and 2215 participants in the control arm). The overall median of follow-up duration was 4.6 years (interquartile interval 4.4-4.9). The achieved adherence rate to polypill in intervention arm was 86%. In the control group, 176 (8.0%) of 2215 participants developed primary outcome, compared with 88 (4.0%) of 2200 participants in the polypill group. We found substantial reduction in risk of primary outcome both in relative and absolute scales (HR 0.50, 95% CI 0.38 to 0.65; absolute risk reduction 4.0%, 95% CI 2.5% to 5.3%). No difference in serious adverse events was observed between the two groups. CONCLUSIONS: The fixed-dose combination therapy using polypill can safely halve the risk of major cardiovascular diseases at the population level. TRIAL REGISTRATION NUMBER: NCT03459560.

Meta-analysis: Risk of pancreatic cancer in patients with inflammatory bowel disease.

BACKGROUND: Studies exploring the association between inflammatory bowel disease (IBD) and pancreatic cancer have reported inconsistent results. AIMS: To provide a comprehensive overview of the risk of pancreatic cancer development in patients with IBD. METHODS: We searched Embase, PubMed, Scopus and ProQuest from inception to 31 October 2023. We included population-based cohort studies examining the risk of incident pancreatic cancer in adult patients with IBD compared to the non-IBD population. We also retrieved Mendelian randomisation (MR) studies investigating the relationship of IBD with pancreatic cancer risk. We conducted random-effects meta-analyses and provided pooled relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: We included 13 studies. Among 11 cohort studies, the risk of developing pancreatic cancer increased by 79% in patients with IBD (RR = 1.79 [95% CI: 1.16-2.75]; I2 = 95.7%). Patients either with Crohn's disease (RR = 1.42 [95% CI: 1.24-1.63]) or ulcerative colitis (RR = 1.50 [95% CI: 1.17-1.92]) had increased risk (p for interaction = 0.72). The annual incidence of pancreatic cancer potentially attributable to IBD increased by 55 cases (95% CI: 17-103) per million. Two MR studies demonstrated that genetic liability to IBD was associated with an increased risk of pancreatic cancer. CONCLUSIONS: Our results suggest a moderate increase in the risk of pancreatic cancer in patients with IBD, which may be further heightened by genetic predisposition to IBD. The increased risk of pancreatic cancer is probably similar in Crohn's disease and ulcerative colitis.

The Mutographs biorepository: A unique genomic resource to study cancer around the world.

Large-scale biorepositories and databases are essential to generate equitable, effective, and sustainable advances in cancer prevention, early detection, cancer therapy, cancer care, and surveillance. The Mutographs project has created a large genomic dataset and biorepository of over 7,800 cancer cases from 30 countries across five continents with extensive demographic, lifestyle, environmental, and clinical information. Whole-genome sequencing is being finalized for over 4,000 cases, with the primary goal of understanding the causes of cancer at eight anatomic sites. Genomic, exposure, and clinical data will be publicly available through the International Cancer Genome Consortium Accelerating Research in Genomic Oncology platform. The Mutographs sample and metadata biorepository constitutes a legacy resource for new projects and collaborations aiming to increase our current research efforts in cancer genomic epidemiology globally.

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.

Contribution of genetic variants in the development of familial premature coronary artery disease in a cohort of cardiac patients.

Coronary artery disease (CAD), the most prevalent cardiovascular disease, is the leading cause of death worldwide. Heritable factors play a significant role in the pathogenesis of CAD. It has been proposed that approximately one-third of patients with CAD have a positive family history, and individuals with such history are at ~1.5-fold increased risk of CAD in their lifespans. Accordingly, the long-recognized familial clustering of CAD is a strong risk factor for this disease. Our study aimed to identify candidate genetic variants contributing to CAD by studying a cohort of 60 large Iranian families with at least two members in different generations afflicted with premature CAD (PCAD), defined as established disease at ≤45 years in men and ≤55 years in women. Exome sequencing was performed for a subset of the affected individuals, followed by prioritization and Sanger sequencing of candidate variants in all available family members. Subsequently, apparently healthy carriers of potential risk variants underwent coronary computed tomography angiography (CCTA), followed by co-segregation analysis of the combined data. Putative causal variants were identified in seven genes, ABCG8, CD36, CYP27A1, PIK3C2G, RASSF9, RYR2, and ZFYVE21, co-segregating with familial PCAD in seven unrelated families. Among these, PIK3C2G, RASSF9, and ZFYVE21 are novel candidate CAD susceptibility genes. Our findings indicate that rare variants in genes identified in this study are involved in CAD development.

Risk of Common Neurological Disorders in Adult Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Several studies investigated the risks of neurological conditions in patients with inflammatory bowel disease (IBD), with some variability in findings. We aimed to perform a systematic review and meta-analysis of available evidence to elucidate the association between IBD and the risks of common neurological disorders. METHODS: We conducted a literature search through Embase, PubMed, Scopus, and ProQuest databases from inception to June 30, 2023, to identify cohort studies assessing the risk of developing stroke, all-cause dementia, Parkinson's disease (PD), multiple sclerosis (MS), seizure/epilepsy, and peripheral neuropathy in adult IBD patients compared with non-IBD population. We combined hazard ratios (HRs) with 95% confidence intervals (CIs) to compute pooled estimates using a random-effects model. RESULTS: In total, 22 cohort studies were included, of which 9 studies reported 7074 stroke events in 202 460 IBD patients, 5 studies reported 3783 all-cause dementia diagnoses in 109 602 IBD patients, 7 studies reported 932 PD diagnoses in 354 792 IBD patients, and 1 study reported 6 MS events in 35 581 IBD patients. We observed increased risks of incident stroke (pooled HR = 1.19; 95% CI, 1.06-1.31), all-cause dementia (pooled HR = 1.22; 95% CI, 1.05-1.38), PD (pooled HR = 1.39; 95% CI, 1.20-1.58), and MS (HR = 2.89; 95% CI, 1.02-8.42). No eligible studies were found on peripheral neuropathy and seizure/epilepsy. CONCLUSIONS: Inflammatory bowel disease may be modestly associated with increased risks of stroke, all-cause dementia, and PD. Further longitudinal studies are warranted to investigate potential links with MS, seizure/epilepsy, and peripheral neuropathy, as well as their clinical significance.

This systematic review and meta-analysis of cohort studies aimed to clarify association between inflammatory bowel disease and risks of common neurological disorders. Based on analyses, inflammatory bowel disease may modestly increase risks of stroke, all-cause dementia, and Parkinson's disease vs the healthy population.

Breast cancer incidence trends in Golestan, Iran: An age-period-cohort analysis by ethnic region, 2004-2018.

BACKGROUND: We aimed to examine the effects of age, diagnosis year (calendar period) and birth year (cohort) on the incidence trends of breast cancer among Golestan women, Northeast Iran, 2004-2018. METHODS: Incidence data were obtained by residential status (urban/rural) and ethnic region (Turkmens/non-Turkmens). We calculated age-standardized incidence rates (ASRs) per 100,000 person-years. The estimated annual percentage change (EAPC) were calculated, and age-period-cohort (APC) models fitted to assess non-linear effects of period and cohort as incidence rate ratios (IRRs). RESULTS: The total number of female breast cancer cases in Golestan, 2004-2018, were 3853, with an overall ASR of 31.3. We found higher rates in urban population (40.5) and non-Turkmens region (38.5) compared to rural area (20.8) and Turkmens region (20.2), respectively. There were increasing trends in incidence rates overall (EAPC= 4.4; 95%CI: 2.2, 6.7), with greater changes in rural areas (EAPC=5.1), particularly among non-Turkmens (EAPC=5.8). The results of the APC analysis indicate the presence of significant non-linear cohort effects with increasing IRRs across successive birth cohorts (IRR=0.1 and IRR= 2.6 for the oldest and the youngest birth cohorts vs. the reference birth cohort, respectively). CONCLUSION: We found increasing trends in breast cancer incidence among Golestan women over the study period, with disparities in patterns and trends by residence area and ethnic region. The observed cohort effects suggest an increasing prevalence of key risk factors for breast cancer in this Iranian population. Further investigations are warranted to clarify the relationships between determinants such as reproductive factors and ethnicity in the region.

Unveiling an Association between Waterpipe Smoking and Bladder Cancer Risk: A Multicenter Case-Control Study in Iran.

BACKGROUND: Limited data exist for the association between bladder cancers and waterpipe smoking, an emerging global public health concern. METHODS: We used the IROPICAN database in Iran and used multivariable logistic regression, adjusting for cigarette smoking, opium use, and other confounding factors. In addition, we studied the association between exclusive waterpipe smoking and bladder cancer. RESULTS: We analyzed 717 cases and 3,477 controls and a subset of 215 patients and 2,145 controls who did not use opium or cigarettes. Although the OR adjusted for opium, cigarettes, and other tobacco products was 0.92 [95% confidence interval (CI), 0.69-1.20], we observed a statistically significant elevated risk in exclusive waterpipe smokers (OR = 1.78; 95% CI, 1.16-2.72) compared with non-users of opium or any tobacco. Associations were strongest for smoking more than two heads/day (OR = 2.25; 95% CI, 1.21-4.18) and for initiating waterpipe smoking at an age less than 20 (OR = 2.73; 95% CI, 1.11-6.72). The OR for urothelial bladder cancer was higher in ex-smokers (OR = 2.35; 95% CI, 1.24-4.42) than in current smokers (OR = 1.52; 95% CI, 0.72-3.15). All observed associations were consistently higher for urothelial histology. CONCLUSIONS: Waterpipe smoking may be associated with an increased risk of bladder cancer, notably among individuals who are not exposed to cigarette smoking and opium. IMPACT: The study provides compelling evidence that waterpipe smoking is a confirmed human carcinogen, demanding action from policymakers. See related In the Spotlight, p. 461.

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.

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.

Prevalence and determinants of opioid use disorder among long-term opiate users in Golestan Cohort Study.

BACKGROUND: Number of opiate users worldwide has doubled over the past decade, but not all of them are diagnosed with opioid use disorder. We aimed to identify the prevalence and risk factors for OUD after ten years of follow-up. METHODS: Among 8,500 chronic opiate users at Golestan Cohort Study baseline (2004-2008), we recalled a random sample of 451 subjects in 2017. We used three questionnaires: a questionnaire about current opiate use including type and route of use, the drug use disorder section of the Composite International Diagnostic Interview lifetime version, and the validated Kessler10 questionnaire. We defined opioid use disorder and its severity based on the DSM-5 criteria and used a cutoff of 12 on Kessler10 questionnaire to define psychological distress. RESULTS: Mean age was 61.2 ± 6.6 years (84.7% males) and 58% were diagnosed with opioid use disorder. Starting opiate use at an early age and living in underprivileged conditions were risk factors of opioid use disorder. Individuals with opioid use disorder were twice likely to have psychological distress (OR = 2.25; 95%CI: 1.44-3.52) than the users without it. In multivariate regression, former and current opiate dose and oral use of opiates were independently associated with opioid use disorder. Each ten gram per week increase in opiate dose during the study period almost tripled the odds of opioid use disorder (OR = 3.18; 95%CI: 1.79-5.63). CONCLUSIONS: Chronic opiate use led to clinical opioid use disorder in more than half of the users, and this disorder was associated with psychological distress, increasing its physical and mental burden in high-risk groups.

Polypharmacy and pattern of medication use among patients with gastroesophageal reflux disease: results from Pars Cohort study.

BACKGROUND: Gastroesophageal Reflux Disease (GERD) is a common chronic condition. Its chronic nature may affect the pattern of medication use. This study aimed to investigate the prevalence, associated factors, and patterns of polypharmacy and medication use among GERD patients in southwestern Iran. METHODS: We used data from the Pars Cohort Study. We classified drugs using the Anatomical Therapeutic Chemical classification system. The Lexicomp® database was used to assess potential drug-drug interactions. Multivariable Poisson regression was applied. Adjusted prevalence ratio (PR) and its 95% confidence interval (CI) were estimated. RESULTS: A total of 9262 participants were included. Among 2,325 patients with GERD, age-standardized prevalence of polypharmacy was 9.5% (95% CI: 7.5%, 11.6%) in males, and 19.3% (95% CI: 17.2%, 21.4%) in females. The PR of experiencing Polypharmacy by GERD patients compared to non-GERD patients was 1.82 (95% CI: 1.61, 2.05%). Multimorbidity (PR: 3.33; CI: 2.66, 4.15), gender (PR: 1.68; CI: 1.30, 2.18), and metabolic syndrome (PR: 1.77; CI: 1.45, 2.15) were associated with polypharmacy among GERD patients. Drugs for acid-related disorders were the most common used drugs among men, women and elders. We found that 13.9%, 4.2%, and 1.1% of GERD patients had type C, D and X drug interactions, respectively. CONCLUSION: GERD is correlated with a higher prevalence of polypharmacy. Among GERD patients, females, those with multi-morbidities, and those with metabolic syndrome may be affected more by polypharmacy. Considering the fairly high rate of interactions identified, a review of the medication list is essential when approaching GERD patients, and physicians must check for medications that may worsen GERD.

Opium use and risk of colorectal cancer: a multi-center case-referent study in Iran.

BACKGROUND: Opium use has been associated with an increased risk of cancers of the lung, oesophagus, and pancreas, and it was recently classified by the International Agency for Cancer Research as carcinogenic to humans. It is not clear whether opium also increases the risk of colorectal cancer (CRC). The aim of our study was to assess the association between various metrics of opium use and the risk of CRC. METHODS: This case-referent study from seven provinces in Iran comprised 848 CRC cases and 3215 referents. Data on opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure odds ratios (OR) adjusted for age, gender, province, marital status, family history of CRC-linked cancers, consumption of red meat, fruits and vegetables, body shape, occupational physical activity, and socioeconomic status. RESULTS: Regular opium consumption was not associated with the risk of CRC (OR 0.9, 95% confidence interval, CI: 0.7, 1.2) compared to subjects who never used opium. However, frequent opium use more than twice a day was associated with an increased risk of CRC compared to non-users of opium (OR: 2.0, 95% CI: 1.1, 3.8; p for quadratic trend 0.008). CONCLUSION: There seems to be no overall association between opium use and CRC, but the risk of CRC might be increased among persons who use opium many times a day.

Liver fibrosis in pars cohort study: A large-scale study on the prevalence and correlated factors.

BACKGROUNDS AND STUDY AIMS: The fibrosis-4 (FIB-4) is a non-invasive scoring system for estimating liver fibrosis severity as a biomarker of chronic liver disease. We aimed to estimate the prevalence and severity of chronic liver disease at the community level using FIB-4. PATIENTS AND METHODS: This cross-sectional study was conducted using the Pars Cohort database collected in Valashar, Fars province, Iran. Participants were divided into three groups based on their FIB-4 scores: low risk of liver fibrosis (FIB < 1.45), intermediate cases (1.45 ≤ FIB-4 ≤ 3.25), and high risk of liver fibrosis (FIB-4 > 3.25). RESULTS: In total, 9269 individuals with a mean age of 52.65 years were enrolled in the study, of which 4278 (46.2 %) were male. Among all participants, 7853 (84.7 %) were in the low-risk, and 65 (0.7 %) were in the high-risk groups. In the final ordinal regression model, male gender, being a farmer or rancher, living in rural areas, history of opioid use, history of jaundice, no history of diabetes, history of depression, and positive HBs Ag were independently associated with higher FIB-4 scores. CONCLUSION: Our study revealed that males, individuals residing in rural areas, and those engaged in farming and ranching occupations face a heightened risk of liver fibrosis. These findings emphasize the need for future programs for early detection and effective management of liver fibrosis in these at-risk populations.

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.