Opium use and risk of lung cancer: A multicenter case-control study in Iran.

Opium use was recently classified as a human carcinogen for lung cancer by the International Agency for Research on Cancer. We conducted a large, multicenter case-control study evaluating the association between opium use and the risk of lung cancer. We recruited 627 cases and 3477 controls from May 2017 to July 2020. We used unconditional logistic regression analyses to estimate the odds ratios (OR) and 95% confidence intervals (CI) and measured the association between opium use and the risk of lung cancer. The ORs were adjusted for the residential place, age, gender, socioeconomic status, cigarettes, and water pipe smoking. We found a 3.6-fold risk of lung cancer for regular opium users compared to never users (95% CI: 2.9, 4.6). There was a strong dose-response association between a cumulative count of opium use and lung cancer risk. The OR for regular opium use was higher for small cell carcinoma than in other histology (8.3, 95% CI: 4.8, 14.4). The OR of developing lung cancer among opium users was higher in females (7.4, 95% CI: 3.8, 14.5) than in males (3.3, 95% CI: 2.6, 4.2). The OR for users of both opium and tobacco was 13.4 (95% CI: 10.2, 17.7) compared to nonusers of anything. The risk of developing lung cancer is higher in regular opium users, and these results strengthen the conclusions on the carcinogenicity of opium. The association is stronger for small cell carcinoma cases than in other histology.

Association Between Incident Type 2 Diabetes and Opium Use: Mediation by Body Mass and Adiposity.

Opiates can affect glucose metabolism and obesity, but no large prospective study (to our knowledge) has investigated the association between long-term opium use, body mass index (BMI; weight (kg)/height (m)2), and incident type 2 diabetes mellitus (T2DM). We analyzed prospective data from 50,045 Golestan Cohort Study participants in Iran (enrollment: 2004-2008). After excluding participants with preexisting diseases, including diabetes, we used adjusted Poisson regression models to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for T2DM in opium users compared with nonusers, using mediation analysis to assess the BMI-mediated association of opium use with incident T2DM. Of 40,083 included participants (mean age = 51.4 (standard deviation, 8.8) years; 56% female), 16% were opium users (median duration of use, 10 (interquartile range), 4-20) years). During follow-up (until January 2020), 5,342 incident T2DM cases were recorded, including 8.5% of opium users and 14.2% of nonusers. Opium use was associated with an overall decrease in incident T2DM (IRR = 0.83, 95% CI: 0.75, 0.92), with a significant dose-response association. Most (84.3%) of this association was mediated by low BMI or waist circumference, and opium use did not have a direct association with incident T2DM (IRR = 0.97, 95% CI: 0.87, 1.08). Long-term opium use was associated with lower incidence of T2DM, which was mediated by low body mass and adiposity.

Opium Use and Cancer Risk: A Comprehensive Systematic Review and Meta-Analysis of Observational Studies.

Background: Epidemiological studies have reported inconsistent associations between opium use and cancer risk. We therefore conducted a systematic review and meta-analysis to investigate the relationship between opium use and cancer risk. Methods: We searched PubMed, Scopus, ISI Web of Knowledge, and Google Scholar until February 2021 and references of retrieved relevant articles for observational studies that reported the risk of cancer in relation to opium use. Random-effects models were used to calculate pooled effect sizes (ESs) as well as 95% confidence intervals (CIs) for the association between opium use and cancer risk by considering opium doses and types, duration of consumption, and routes of opium use. Results: In total, 21 observational articles, with a total sample size of 64,412 individuals and 6,658 cases of cancer, were included in this systematic review and meta-analysis. Ever opium users, compared with never opium users, had 3.53 times greater risk of overall cancer (pooled ES: 3.53, 95% CI: 2.60-4.79, P ≤ 0.01). This positive association was also seen for some individual types of cancers except for esophageal and colon cancers. Also, we found that higher opium doses and higher duration of consumption were associated with an increased risk of overall and individual types of cancer. However, the associations between opium doses and the risk of head and neck and larynx cancers were not significant. In terms of the routes of opium use, both opium ingestion and smoking were positively associated with the risk of cancer. Regarding opium types, we found that using teriak, but not shireh, could increase the risk of cancer. Conclusions: Our findings showed that opium use, particularly in the form of teriak, is a risk factor for cancer.

Incidence, early case fatality and determinants of stroke in Iran: Golestan Cohort Study.

OBJECTIVES: While few studies investigated the incidence of stroke in Iran, no Iranian cohort has estimated the standardized-incidence rate and early fatality of first-ever-stroke subtypes along with associated factors. METHODS: Golestan Cohort Study is a prospective study launched in northeastern Iran in 2004, including 50,045 individuals aged 40-75 at baseline. Age-standardized incidence rate of first-ever-stroke was calculated per 100,000 person-years, according to World Standard Population. The 28-day case fatality was calculated by dividing the number of fatal first-ever-stroke during the first 28 days by total events. Cox proportional hazard models were conducted to assess incidence and fatality risk factors. We used Population Attributable Fractions to estimate the incidence and early fatality proportions reduced by ideal risk factor control. RESULTS: 1,135 first-ever-strokes were observed during 8.6 (median) years follow-up. First-ever-stroke standardized incidence rate was estimated 185.2 (95% CI: 173.2-197.2) per 100,000 person-years. The 28-day case fatality was 44.1% (95% CI: 40.4-48.2). Hypertension and pre-stroke physical activity were the strongest risk factors associated with first-ever-stroke incidence (Hazard ratio: 2.83; 2.47-3.23) and 28-day case fatality (Hazard ratio: 0.59; 0.44-0.78), respectively. Remarkably, opium consumption was strongly associated with hemorrhagic stroke incidence (Hazard ratio: 1.52; 1.04-2.23) and ischemic stroke fatality (Hazard ratio: 1.44; 1.01-2.09). Overall, modifiable risk factors contributed to 83% and 61% of first-ever-stroke incidence and early fatality, respectively. CONCLUSION: Efficient risk factor control can considerably reduce stroke occurrence and fatality in our study. Establishing awareness campaigns and 24-hour stroke units seem necessary for improving the stroke management in this area.

Opium use and risk of mortality from digestive diseases: a prospective cohort study.

OBJECTIVES: Opium use, particularly in low doses, is a common practice among adults in northeastern Iran. We aimed to investigate the association between opium use and subsequent mortality from disorders of the digestive tract. METHODS: We used data from the Golestan Cohort Study, a prospective cohort study in northeastern Iran, with detailed, validated data on opium use and several other exposures. A total of 50,045 adults were enrolled during a 4-year period (2004-2008) and followed annually until December 2012, with a follow-up success rate of 99%. We used Cox proportional hazard regression models to evaluate the association between opium use and outcomes of interest. RESULTS: In all, 8,487 (17%) participants reported opium use, with a mean duration of 12.7 years. During the follow-up period 474 deaths from digestive diseases were reported (387 due to gastrointestinal cancers and 87 due to nonmalignant etiologies). Opium use was associated with an increased risk of death from any digestive disease (adjusted hazard ratio (HR)=1.55, 95% confidence interval (CI)=1.24-1.93). The association was dose dependent, with a HR of 2.21 (1.57-3.31) for the highest quintile of cumulative opium use vs. no use (Ptrend=0.037). The HRs (95% CI) for the associations between opium use and malignant and nonmalignant causes of digestive mortality were 1.38 (1.07-1.76) and 2.60 (1.57-4.31), respectively. Increased risks were seen both for smoking opium and for ingestion of opium. CONCLUSIONS: Long-term opium use, even in low doses, is associated with increased risk of death from both malignant and nonmalignant digestive diseases.

Lead poisoning among asymptomatic individuals with a long-term history of opiate use in Golestan Cohort Study.

BACKGROUND: Recent reports of lead poisoning suggest that people who use opium may be exposed to high amounts of lead. Here, we investigate the association between opium use and blood lead levels (BLL) in a population-based cohort study. METHODS: In 2017, we studied a random sample of 410 people who currently (both within the past year and the past month) used opium and 104 who did not from participants of the Golestan Cohort Study in northeast Iran. Participants were stratified by sex and tobacco use history, completed a comprehensive opiate and tobacco use questionnaire and provided blood. BLL was measured by Lead Care® II Blood Lead Test Kit, validated by inductively coupled plasma triple quadrupole mass spectrometry. BLL was categorized as "<5 µg/dL", "elevated" (5-10 µg/dL), "high" (10-50 µg/dL), and "very high" (above 50 µg/dL). To assess the association between BLL categories and opiate use, route of consumption and weekly use, we used ordered logistic regression models, and report OR (odds ratio) and 95% CI (confidence interval) adjusted for age, sex, place of residence, education, occupation, household fuel type, and tobacco use. RESULTS: In the cohort, participants used only raw (teriak) or refined (shireh) opium, which were smoked (45%, n = 184), taken orally (46%, n = 189), or both (9%, n = 37), for a mean duration of 24.2 (standard deviation: 11.6) years. The median BLL was significantly higher in people who currently used opium (11.4 µg/dL; IQR: 5.2-23.4) compared with those who did not (2.3 µg/dL; IQR: 2.3-4.2), and the highest median BLL was seen in oral use (21.7 µg/dL; IQR: 12.1-34.1). The BLL was <5 µg/dL among 79.8% of people with no opiate use, compared with only 22.7% in those using opium. BLL was elevated in 21.7%, high in 50.5% and very high in 5.1% of people using opium. About 95% of those with oral (180/189) or dual use (35/37) and 55% (102/184) of those who smoked opium had levels of blood lead above 5 µg/dL. The OR for the association between any opium use and each unit of increase in BLL category was 10.5 (95%CI: 5.8-19.1), and oral use of opium was a very strong predictor of increasing BLL category (OR=74.1; 95%CI: 35.1-156.3). This odds ratio was 38.8 (95%CI: 15.9-95.1) for dual use and 4.9 (95%CI: 2.6-9.1) for opium smoking. There was an independent dose-response association between average weekly dose and BLL among people using opium, overall and when stratified by route of use. CONCLUSION: Our results indicate that regular use of lead-adulterated opium can expose individuals to high levels of lead, which may contribute to mortality and cancer risks associated with long-term opium use.

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

BACKGROUND: Bladder cancer (BC) is the 10th most common type of cancer worldwide and the fourth most common type of cancer in Iran. Opium use is considered as one of the risk factors for BC. We aim to assess the association between various parameters of opium use, which in Iran is mainly ingested or smoked in various forms, and the risk of BC. METHOD: In this multi-centre case-referent study in Iran, 717 BC cases and 3477 referents were recruited to the study from May 2017 until July 2020. Detailed histories of opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure adjusted odds ratio (OR) and 95% confidence intervals (CI). The ORs were adjusted for age, gender, place of residence and pack-years of cigarette smoking. RESULTS: Regular opium consumption was associated with an increased risk of BC (OR 3.5, 95% CI: 2.8, 4.3) compared with subjects who never used opium. Compared with continuous users, the risk decreased to one-third for those who stopped opium more than 10 years ago. The adjusted OR for those who used both crude opium (teriak) and opium juice was 7.4 (95% CI: 4.1, 13.3). There was a joint effect of opium and tobacco (OR for users of both opium and tobacco 7.7, 95% CI: 6.0, 9.7). CONCLUSIONS: Regular opium use is associated with an approximately 4-fold risk for BC. The OR decreases along with the increasing time since stopping opium use.

The marginal causal effect of opium consumption on the upper gastrointestinal cancer death using parametric g-formula: An analysis of 49,946 cases in the Golestan Cohort Study, Iran.

Upper gastrointestinal (UGI) cancer, including esophageal and gastric, is one of the most common cancers in the world. Hence, the determination of risk factors of UGI helps to reduce the economic and social burden of this cancer in communities. In Iran, the consumption of opium because of its neighborhood with Afghanistan are considerable. In this study, we examine the causal effect of opium use on the time to UGI cancer death. Based on the Golestan Cohort Study (GCS) in northeastern of Iran, about 50000 adults were enrolled to the study for four years (2004-2008) and followed annually until July 2018. We used "parametric g-formula" to study the causal effect of opium use on the time to death due to UGI. In this study, the information of 49946 individuals due to missingness were analyzed. So the median of follow-up time was 144 months and the prevalence of opium use was 17% (about 8489 persons). During the follow-up period, 593 (1.2%) death from upper gastrointestinal cancer were reported. The study showed that the effect of opium use on the time to UGI death was statistically significant (adjusted risk-ratio based on parametric g-formula = 1.31, 95% CI: [1.04, 1.65]). Additionally, the Population Attributable Fraction (PAF) in UGI cancer deaths of opium use was estimated 5.3% (95% CI: [0.6%, 11.3%]). Our results showed a causal effect of opium use on the intensity of upper gastrointestinal cancer death.

The Iranian Study of Opium and Cancer (IROPICAN): Rationale, Design, and Initial Findings.

BACKGROUND: The International Agency for Research on Cancer (IARC) recently classified opium use as a Group 1 carcinogen. However, much remains to be studied on the relation between opium and cancer. We designed the Iranian Opium and Cancer (IROPICAN) study to further investigate the association of opium use and cancers of the head and neck, bladder, lung, and colon and rectum. In this paper, we describe the rationale, design, and some initial results of the IROPICAN Study. METHODS: The IROPICAN is a multi-center case-control study conducted in 10 provinces of Iran. The cases were all histologically confirmed and the controls were selected from hospital visitors who were free of cancer, were not family members or friends of the cancer patients, and were visiting the hospital for reasons other than their own ailment. The questionnaires included detailed questions on opium use (including age at initiation, duration, frequency, typical amount, and route), and potential confounders, such as tobacco use (e.g., cigarettes, nass and water-pipe), and dietary factors. Biological samples, including blood and saliva, were also collected. RESULTS: The validation and pilot phases showed reasonably good validity, with sensitivities of 70% and 69% for the cases and controls, respectively, in reporting opium use. The results also showed excellent reliability, with intra-class correlation coefficients of 0.96 for ever opium use and 0.88 (95% CI: 0.80, 0.92) for regular opium use. In the main phase, we recruited 3299 cancer cases (99% response rate) and 3477 hospital visitor controls (89% response rate). The proportion of ever-use of opium was 40% among cases and 18% among controls. CONCLUSION: The IROPICAN study will serve as a major resource in studies addressing the effect of opium on risk of cancers of the head and neck, bladder, lung, and colon and rectum.

Smoking Water-Pipe, Opium Use and Prevalence of Heart Disease: A Cross-sectional Analysis of Baseline Data from the Pars Cohort Study, Southern Iran.

BACKGROUND: Associations between hookah and opium use and an increased risk of ischemic heart disease (IHD) have been suggested in a few studies, but more research is needed on the nature of these associations. We aimed to investigate the association between hookah and opium use and the prevalence of IHD in a population with relatively high prevalence of these exposures in Iran. METHODS: Using baseline data from the Pars Cohort Study (PCS), a prospective study of individuals aged 40-75 years in Fars province, southern Iran, we calculated adjusted and crude odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the independent association of hookah and opium use with prevalence of IHD. RESULTS: Of 9248 participants, 10.2% (95% CI: 9.5, 10.9) had self-reported IHD. Prevalence of ever use of hookah and opium was 48.9% (95% CI: 44.6, 53.6) and 10.2% (95% CI: 8.3, 12.5) among those with IHD, and 37.0% (95% CI: 35.7, 38.3) and 8.1% (95% CI: 7.5, 8.7) among those without IHD, respectively. Adjusted OR for the association with prevalence of IHD was 1.26 (95% CI: 1.08, 1.46) for hookah use and 1.71 (95% CI: 1.30, 2.24) for opium abuse. No dose-response association was found between hookah and prevalence of IHD. CONCLUSION: Hookah and opium abuse were associated with prevalent IHD in this study. Although more research is needed on these associations, particularly in prospective settings, reducing hookah and opium use could potentially reduce IHD risk.

Epidemiologic Study of Opium Use in Pars Cohort Study: A Study of 9000 Adults in a Rural Southern Area of Iran.

BACKGROUND: Opium is one of the most common substances used worldwide with variable epidemiologic features in different regions. This study was performed in southern Iran, to find the epidemiology of opium use and its association with different factors and diseases. METHODS: This cross-sectional study was performed on baseline data extracted from Pars Cohort Study performed in Valashahr, a rural area in southern Iran. For any subject, information was collected about demographic factors, some common diseases including heart disease, stroke and hypertension and the state of using opium, other substances and cigarettes. RESULTS: There were 4276 males and 4988 females, with a mean age of 52.6 ± 9.7 years of whom 8.4% reported opium use (17.3% of males and 0.7% of females). In men, the history of stroke and heart disease were significantly more common in opium users (12.6% vs. 8.8%, P = 0.001 and 2.8% vs. 1.5%, P = 0.01, respectively) while the history of hypertension was significantly more common in non-opium users (7.8% vs. 10.3%, P = 0.04). Younger age, male gender, being non-married and positive history of joint pain, cigarette smoking and alcohol consumption were the factors associated with opium use. CONCLUSION: Opium use is common in non-married men who have a positive history of cigarette smoking and alcohol consumption in the rural population of southern Iran. It is associated with increased risk of heart disease and stroke and decreased risk of hypertension in males. Global interventional and preventive measures are required to control this complicated social problem.

Opium use, cigarette smoking, and alcohol consumption in relation to pancreatic cancer.

BACKGROUND AND AIMS: Although several studies have suggested opium as a risk factor for cancers of the esophagus, stomach, larynx, lung, and bladder, no previous study has examined the association of opium with pancreatic cancer. We aimed to study the association between opium use and risk of pancreatic cancer in Iran, using a case-control design. We also studied the association of cigarette smoking and alcohol consumption with pancreatic cancer, for which little information was available from this population. METHODS: Cases and controls were selected from patients who were referred to 4 endoscopic ultrasound centers in Tehran, Iran. We recruited 316 histopathologically (all adenocarcinoma) and 41 clinically diagnosed incident cases of pancreatic cancer, as well as 328 controls from those with a normal pancreas in enodosonography from January 2011 to January 2015. We used logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: After adjustment for potential confounders, opium use (OR 1.91; 95% CI 1.06-3.43) and alcohol consumption (OR 4.16; 95% CI 1.86-9.31) were significantly associated with an increased risk of pancreatic cancer. We did not find an association between ever tobacco smoking and pancreatic cancer risk (OR 0.93; 95% CI 0.62-1.39). CONCLUSION: In our study, opium use and alcohol consumption were associated with an increased risk of pancreatic cancer, whereas cigarette smoking was not.

Determinants of gastroesophageal reflux disease, including hookah smoking and opium use- a cross-sectional analysis of 50,000 individuals.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common cause of discomfort and morbidity worldwide. However, information on determinants of GERD from large-scale studies in low- to medium-income countries is limited. We investigated the factors associated with different measures of GERD symptoms, including frequency, patient-perceived severity, and onset time. METHODS: We performed a cross-sectional analysis of the baseline data from a population-based cohort study of ∼ 50,000 individuals in in Golestan Province, Iran. GERD symptoms in this study included regurgitation and/or heartburn. RESULTS: Approximately 20% of participants reported at least weekly symptoms. Daily symptoms were less commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use, lower socioeconomic status, and lower physical activity were associated with daily symptoms. Most of these factors showed similar associations with severe symptoms. Women with higher BMI and waist to hip ratio were more likely to report frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02-1.75) and opium use (OR 1.70, 95% CI 1.55-1.87) were associated with severe symptoms, whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76-0.99). After exclusion of cigarette smokers, hookah smoking was still positively associated and nass chewing was inversely associated with GERD symptoms (all frequencies combined). CONCLUSION: GERD is common in this population. The associations of hookah and opium use and inverse association of nass use with GERD symptoms are reported for the first time. Further studies are required to investigate the nature of these associations. Other determinants of GERD were mostly comparable to those reported elsewhere.