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.

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.

Is opium use associated with an increased risk of lung cancer? A case-control study.

BACKGROUND: In recent years, lung cancer (LC) incidence has increased in Iran. The use of opium and its derivatives (O&D) has increased as well. This study aimed to investigate the association between the use of O&D and LC incidence. METHODS: In this case-control study conducted in Kerman, Iran; 140 patients with lung cancer and 280 healthy controls matched by age, sex, and place of residence were included. Data, including O&D use, cigarette smoking, alcohol use, and diet, were collected using a structured questionnaire. The relation between the use of O&D and LC was evaluated using conditional logistic regression adjusted for tobacco smoking, education, daily intake of fruit, vegetables, red meat, and hydrogenated fats. RESULTS: Opium ever-use was associated with an increased risk of LC (Adjusted Odds Ratio (AOR) =5.95, 95% CI: 1.87-18.92). Participants were divided into low and high use groups based on the median of opium use in the control group. A significant dose-response relation was observed between the amount of daily O&D use and LC; and the relation was stronger in high users (AOR low users = 3.81% CI: 1.13-12.77 and OR high users = 9.36, 95% CI: 2.05-42.72). Also, LC was higher among participants starting the use of O&D at younger ages (≤ 41 years old vs never users AOR = 8.64, 95% CI: 1.90-39.18) compared to those who started at an older age (> 41 years old vs never users, AOR = 4.71, 95% CI: 1.38-16.08). The association between opium, and lung cancer among non-smokers was OR: 6.50 (95% CI: 2.89 to 14.64). CONCLUSION: The results of this study show that opium use is probably a dose related risk factor for lung cancer.

Is opium use related to the increased risk of oral cavity cancers? A case-control study in Iran.

BACKGROUND: Oral cavity cancers (OCCs) are the sixth most prevalent cancers in the world. There are strong evidences showing the risk of the cigarette smoking, alcohol use, poor oral hygiene and some types of diets in OCCs; however, few studies explored the relationship between opium and its derivatives (O&D) use and OCCs incidence. The aim of this study was to investigate the relationship between consumption of O&D and the incidence of OCCs. METHODS: In a case-control; 133 patients with OCCs and 266 healthy controls matched by age, sex, and place of residence were included. Data, including cigarette smoking, O&D, alcohol and others tobacco (Nass, pipe and hookah) use and diet, were collected using a structured questionnaire. The relation between the use of O&D and OCCs was evaluated using conditional logistic regression. RESULTS: Opium ever-use was associated with an increased risk of OCCs (Adjusted Odds Ratio (AOR) =2.36, 95 % CI: 1.16-4.78). A dose-response relation was observed between the amount of daily O&D use and OCCs; and the relation was stronger in high users (AOR for low users = 1.38, 95 %CI: 0.58-3.24 and AOR for high users = 4.85, 95 % CI:1.79-13.11). Those who used opium for more than 18 years were highly at risk of OCCs (AOR= 5.04, 95 % CI, 2.00-12.68). Also, OCCs was higher among subjects starting the use of O&D at younger ages (≤ 50 years old vs never users AOR = 3.32, 95 % CI: 1.19-9.23). The smoking method of consuming O&D increased the odds of getting OCCs more than twice (AOR= 2.02, 95 % CI, 1.03-3.94), and using both smoking and oral consumption simultaneously, increased the odds of getting OCCs more than 8 times (AOR= 8.57, 95 % CI, 1.68-43.70). Also, the use of other tobacco products (Nass, pipe and hookah) increases the odds of getting OCCs by 4 times (AOR= 3.90, 95 % CI, 1.12-13.57) CONCLUSIONS: The results showed that opium use is probably a dose related risk factor for oral cavity cancers. Therefore, it is necessary to implement preventive policies to control the use of opioids.

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.

Opium Use and the Risk of Liver Cancer: A Case-Control Study.

Limited evidence is available to acknowledge the association between opium use and liver cancer. In a case-control study, we recruited 117 cases of primary liver cancer (PLC) and 234 age and sex-matched neighborhood controls from 2016 to 2018. We calculated odds ratios (OR) for opium use and 95% confidence intervals (95% CI), using conditional logistic regressions. Compared with non-users the adjusted OR (AOR, 95% CI) for opium use was 6.5 (95% CI, 2.87-13.44). Compared with people who had no history of use, a strong dose-response effect of opium use was observed by amount of use (AOR, 10.70; 95% CI, 3.92-28.70). Cumulative use of opium also indicated that using over 30 gr-year could increase the PLC risk dramatically (AOR, 11.0; 95% CI, 3.83-31.58). Those who used opium for more than 21 years were highly at risk of PLC (AOR, 11.66; 95% CI, 4.43-30.67). The observed associations were significant even among never tobacco smokers (including cigarette and water-pipe smoking). PREVENTION RELEVANCE: The results of this study indicate that opium use dramatically increased the risk of liver cancer. Because opioids are increasing for medical and non-medical use globally; accordingly, severe health consequences such as liver cancer have to be investigated widely.

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 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.

Opium Use and Head and Neck Cancers: A Matched Case-Control Study in Iran.

BACKGROUND: Head and Neck (H and N) cancers include malignant tumors of the nasal cavity, pharynx, paranasal sinuses, oral cavity, larynx and salivary glands. Opium use might be related to these cancers. The aim of this study was to investigate the relation between Opium and its Derivatives (O and D) use and the incidence of H and N cancers. METHODS: In this case-control study conducted in Kerman, 140 patients with HandN cancers and 280 healthy controls (matched for age, gender, and place of residence) were included. Information about their use of O and D, cigarette smoking, alcohol and diet were collected using a structured questionnaire. Conditional logistic regression was used to investigate the relation between variables. RESULTS: The use of opioids was associated with an increased risk of H and N cancers (Adjusted OR: 8.13; CI: 4.08-16.2). A significant dose-response relation between O and D use was observed, with high use Adjusted OR=8.91; 95% CI: 4.03-19.65 and low use Adjusted OR=6.52; 95% CI: 3.18- 13.36. This dose-response association was stronger in patients with laryngeal cancer and opioids use, with high use Adjusted OR = 11.17; 95% CI=4.48-28.09 and low use Adjusted OR = 9.46; 95% CI= 3.97- 22.52. CONCLUSION: The results show that opium use can be considered as an important risk factor for H and N cancers. Also in Iran, opium seems to play a more important role than cigarette smoking.

Opium as a risk factor for upper gastrointestinal cancers: a population-based case-control study in Iran.

BACKGROUND: Gastrointestinal cancers, including esophageal, gastric, liver and pancreatic are relatively common in Iran. Furthermore, consumption of opium and its derivatives (O&D) are considerable. This study, aimed to examine the association between consumption of O&D and the incidence of upper gastrointestinal (UGI) cancers. METHODS: In a matched case-control study in Kerman (located in southeast of Iran), 142 patients with UGI cancers and 284 healthy people (matched in terms of age, sex and residence (urban/rural)) were recruited. Variables (using O&D, smoking, alcohol use and diet) were collected using a structured questionnaire. Conditional logistic regression models were used to assess the above mentioned association. RESULTS: Opium use was associated with an increased risk of UGI cancers with an adjusted OR 4.0 (95% CI=2.2-7.0). A very strong dose-response relation was observed between consumption of O&D and the incidence of UGI cancers. (Three consumption levels-none, low and high; OR=18.7; 95% CI=5.5-63.3). This dose-response relationship was also strong even in patients with gastric cancers (OR=9.2; 95% CI=2.5-33.7). CONCLUSION: The results of this study showed that opium consumption can be a strong risk factor for UGI cancers in Iran.