At an important historical event , Carcinogenicity of Opium Consumption , the most prominent achievement of more than two decades of research efforts of Iranian scientists in the “Golestan Cohort Study ” was confirmed by the International Agency for Research on Cancer of the World Health Organization (IARC / WHO) and it will be published in Volume 126 of the IARC Monographs.
According to the Iran Science Watch (ISW) Carcinogenicity of Opium Consumption was evaluated during the 126th series of the Monographs meetings held virtually from 11-20 September 2020 by IARC (due to The COVID-19 pandemic) with the participation of 16 expert scientists from 10 countries around the world. The results of these assessments were published October 8, 2020 in the Lancet Oncology.
Writer : Fereshteh Hshemi
Iran Science Watch (ISW): isw.ir/en
The Golestan Cohort Study is part of the Gastroesophageal Malignancy in North of Iran (GEMINI) study and one of the largest cohort studies in West Asia and North Africa that was initiated in 2004 by a team of scientists from the Digestive Diseases Research Institute (DDRI) of Tehran University of Medical Sciences (TUMS) led by Professor Reza Malekzadeh in collaboration with the Golestan University of Medical Sciences and scientists from the International Agency for Research on Cancer of the World Health Organization (IARC / WHO), the US National Cancer Institute (NCI / NIH), in Gonbad Kavus city and 326 villages of the Golestan province in Northeast Iran, with an initial aim of identifying the underlying causes of the high rates of esophageal cancer in this region. Since then, the Golestan Cohort Study has collaborated with many international academic and research institutes including Cambridge University , Johns Hopkins University ,Harvard University, Icahn School of Medicine at Mount Sinai, Morgan State University, Karolinska University and University of Toronto.
During more than two decades of research efforts, the Golestan Cohort Study has made significant and unique contributions to the identification of causes of cancer and non-communicable diseases including cardiovascular and cerebrovascular diseases which led to the reception of the IARC Medal of Honor by the founder and principal investigator of the Golestan Cohort Study, Profesor Reza Malekzadeh, in 2018 .
IARC: The evaluation applies only to opium
Monograph 126 evaluates the consumption of opium an addictive narcotic drug . Other opiates, such as heroin, morphine, and codeine, as well as synthetic opioids, such as fentanyl, are outside the scope of this evaluation.
Opium has a complex chemical composition consisting of at least 25 alkaloids
Opium has a complex chemical composition consisting of at least 25 alkaloids (Morphine is one of the most important alkaloids derived from opium ( and other ingredients. The harvested latex of the poppy plant is typically processed by drying or boiling before consumption as opium. Forms of illicit opium that are commonly consumed include raw (or crude) opium, opium dross (tarry residues formed after smoking raw opium, called sukhteh in the Islamic Republic of Iran), and refined opium or opium sap (boiled opium dross with or without added raw opium). All three forms are typically smoked or ingested, and pyrolysis products may result from combustion (smoking) of any form of opium. Opium may be contaminated (or, in the case of illicit opium, adulterated) with lead, other heavy metals, and/or arsenic.
Classification of carcinogens in humans
The IARC Monographs identify environmental factors that have carcinogenic hazards to humans. These include chemicals, complex mixtures, occupational exposures, physical agents, biological agents, and lifestyle factors.
Since 1971, more than 1000 agents have been evaluated, of which more than 400 have been identified as Carcinogenic (Group 1) , Probably Carcinogenic (Group2A) ,Possibly Carcinogenic (Group 2B) and Non Classiffiable (Group3) to humans.
The Monographs assess the strength of the available evidence that an agent can cause cancer in humans, based on three streams of evidence: on cancer in humans ,on cancer in experimental animals , and on mechanistic evidence . In addition, the exposure to each agent is characterized.
Among a variety of studies ,well conducted cohort and case–control studies provide most of the evidence of cancer in humans evaluated by Working Groups.
Classification of Opium Consumption as a Carcinogen
The working group of international experts that participated in the volume 126 of the IARC’S Monographs program, spent more than 17 months in reviewing in details all evidence on the carcinogenicity of opium consumption and then in 10 days discussed all the available evidence that originated from human studies and the mechanistic studies which are included :
–Opium Consumption is Carcinogenic to humans (Group1). The Group1 evaluation is based on sufficient evidence of cancer in human studies. This sufficient evidence determination applies to smoked and ingested routes of raw, dross, and sap opium consumption.
-Evidence in humans was sufficient for cancers of bladder, larynx, and lung.
-Evidence in humans was association for cancers of oesophagus, stomach, pancreas, and pharynx.
-There is strong evidence in experimental systems that opium (sukteh & opium pyrolysates) exhibits key characteristics of carcinogenicity (opium is genotoxic).
Opium Consumption is Carcinogenic to humans
According to the International Agency for Research on Cancer (IARC) there is sufficient evidence in humans for the carcinogenicity of opium consumption and this “sufficient” evidence determination applies to smoked and ingested routes of raw, dross, and sap opium consumption. Therefore, Opium Consumption is Carcinogenic to humans.
The main evidences of opium monograph were from Golestan Cohort Study
Two cohort studies and more than two dozen case-control studies (most hospital-based) carried out across diverse regions and populations of Iran have investigated the association between opium consumption and incident cancers of various sites but the most informative was the Golestan Cohort Study (GCS).
The Golestan Cohort Study, included 50,045 participants, aged 40-75 year old, of whom 17% (8,487 people) reported regular use of different types of minimally processed opium (Raw opium, Shireh and Sukhteh). Over a decade of follow-up , around 8,000 deaths were recorded up to 2019 among the participants, of which 1570 were due to cancer and more than 54% of these cancer deaths were caused by gastrointestinal cancers.
The International Agency for Research on Cancer has described The Golestan Cohort as a study that used a structured questionnaire (validated with urinary levels of opium metabolites), which incorporated questions on opium type mode of consumption, temporality of exposure, duration, intensity and cumulative exposure. The prospective cohort design minimizes concerns regarding selection bias and reverse causation.
The detailed assessment of demographic, socioeconomic, and lifestyle factors addressed concerns regarding major potential confounders, including tobacco smoking. Several unrelated case-control studies also used the GCS questionnaire, while others used different questionnaires, interviews, or patient records to evaluate opium exposure. The amount of detail and quality of exposure information varied considerably across the epidemiological studies.
While individually each study has its limitations, the Working Group concluded that collectively these studies provide a basis to rule out chance, bias, and confounding as alternative explanations for the positive association between opium use and cancers of bladder, larynx, and lung with reasonable certainty; thus, there was suffficient evidence of human arcinogenicity for these three cancer types. Additionally, evidence was deemed to be limited that opium consumption causes cancers of oesophagus, stomach, pancreas, and pharynx.
According to the International Agency for Research on Cancer of the World Health Organization (IARC / WHO) ,in human opium metabolites have been detected in urine, hair, and blood following ingestion or smoking of opium. there was strong evidence in experimental systems that opium, specifically sukhteh and opium pyrolysates, exhibits key characteristics of carcinogens .These opium metabolites are genotoxic.
writer : Fereshteh Hashemi