A Large Multicenter Case-Control Study to Evaluate Association of Opium Use and Risk of Lung, Bladder, Head and Neck and Colorectal Cancers
- To assess sensitivity and specificity of the questionnaire in measurement of opium use in Iranian population;
- To determine association between opium use and lung, colorectal, bladder, and head and neck cancers;
- To determine the role of duration, and dose of opium use in cancer risk;
- To assess geographic variation in association of cancer and opium use;
- To determine the role of route of opium consumption (inhalation, oral use, etc.) on risk of cancer;
- To determine the association between opium metabolites and risk of cancer;
To determine interaction of opium and other established risk factors of cancer including tobacco.
|Target sample size||3200 Cases and 3200 Controls|
|Enrollment update||1586 cases and 1451 controls|
|Website last update date||2018/02/14|
- Opium use and its side effects is an important health problem in Iran.
- Several small studies found association between opium use and risk of cancer. However, there are some concerns on the validity of these findings and it is important to create valid reports about these associations.
- Valid results about this issue will be used to communicate the results with policy makers for cancer prevention programs as well as with the general public for the public awareness programs.
- We have set up a good national and international network to conduct well design study and answer an important public health questions.
- In fact this is four projects and will answer this question about four common cancers which will be done as a package.
- Three PhD students will use the data from this project for their thesis.
- Our international collaborators have promised to use their capacity in their own country and rise further funding, in particular for molecular studies.
- We also hope that we will use benefit from this network and provide an opportunity for our students to apply for international fellowship and experience research environment in the well-known universities in the world.
- In addition to Opium use, we will analyses association of other risk factors like Hookah use, in which the epidemiological data is scarce.
Opium is a substance that extracted from the opium poppy. Derivatives of this substance have useful effect in medicine. For example, opioids drugs derived from this substance have an analgesic application reducing pain in chronic disease like cancer. Moreover, some opioids like codeine have an anti-cough effect [1, 2]. High prevalence of opium use was reported in the Near and Middle East/South-West Asia, primarily in Afghanistan and I.R of Iran . Opium use is considered a criminal behavior and have stigma. In addition, there are laws against its use and distribution in I.R. of Iran. Despite this legislation, prevalence of opium use and other drugs has increased in European countries and was reported 8.7 per 1000 in 50 states of the USA and district of Colombian in 2002-2003 [4-6]. Prevalence of the opium use and its derivatives in Kerman province, which is located in the southern part of Iran, was 17.1% in 2005 . Opium is used in different shapes including Teriak (crude opium), Shire (refined opium extract), and Sukhte (residual opium dross after smoking it) in different part of the Iran [8, 9]. Teriak and Shire can be ingested or smoked, while Sukhte is usually consumed orally .
Epidemiologic studies have reported significant associations between opium use and the risk of different cancers including: lung[10-12], bladder[13-19], oral cavity, larynx, pharynx [20, 21], stomach[22-24] and esophageal [22, 25, 26] cancers. In a recent systematic review, all studies about the association of opium use and cancer have been reviewed. This study reported that there is a significant association between opium use and risk of esophageal, stomach, larynx, and lung and bladder cancer. Interestingly, most of these studies were case-control and were published by Iranian researchers. Only two studies reported the cancer-opium association from other populations, one from Hong Kong  and one from Singapore . Two cohort studies, one from northeast and one from northwest Iran, has so far reported an association between opium use and cancer risk. .
Two mechanisms have been suggested for carcinogenic effect of opium use, including the exposure to opium smoke and the alkaloid component of opium. First, opium users heat the opium to a high temperature and inhale the smoke through particular tube (pipe), when the opium contents starts to vaporize. The opium smoke contains polycyclic aromatic hydrocarbons which is a known carcinogen. In addition, the residual component in the pipe is called Sukhte and can be eaten without any changes or after refinement. Studies have shown that this residual substance have mutagenic role after metabolic activation in Salmonella Typhimurium . This effect can also be caused by morphine and opium pyrolysates . The main carcinogen component of Sukhte consist of all nitrogen containing heterocyclic components derived from pyrolysis of morphine. In the second mechanism, opium contains alkaloid compounds that are absorbed in the body and lead to cancer.
Notwithstanding the several publication on association between opium use and cancer risk, they are usually performed in a small region and could not control for confounding variables properly, In addition, because of small power they could not investigate dose- response relationship, role of starting time of opium use, type and methods of consumption on the risk of cancer. Because opium use is not socially acceptable in Iranian population, the results of epidemiological studies is subject to the selection or measurement bias. However, most of the previous studies did not report response rates and sensitivity and specificity of their questionnaire for assessment of the opium use. Furthermore, available opium products have some additives such as lead, selenium, acetic anhydride, dried blood of animals and addicted persons. Type and amount of additives may vary from region to region. Therefore it is important to consider the role of opium additives in the cancer risk and compare the opium-cancer association between different regions.
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2٫ Zeppetella, G., Opioids for the management of breakthrough cancer pain in adults: a systematic review undertaken as part of an EPCRC opioid guidelines project. Palliative medicine, 2011. 25(5): p. 516-524.
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3٫ world drug report 2013 New York.
4٫ Hamunen, K., et al., What do different databases tell about the use of opioids in seven European countries in 2002? European Journal of Pain, 2008. 12(6): p. 705-715.
5٫ Ishoy, T., L. Haastrup, and G. Hay, Estimating the prevalence of problem opioid use in Copenhagen 1997–۱۹۹۸٫ Danish medical bulletin, 2004. 51: p. 114-116.
6٫ McAdam-Marx, C., et al., Costs of opioid abuse and misuse determined from a Medicaid database. Journal of Pain and Palliative Care Pharmacotherapy, 2010. 24(1): p. 5-18.
7٫ Ziaaddini, H., Ziaaddini, Mohammad Reza, The household survey of drug abuse in Kerman, Iran. Journal of Applied Sciences, 2005. 5(2): p. 380-382.
8٫ Kheirandish, P., et al., Prevalence and correlates of HIV infection among male injection drug users in detention in Tehran, Iran. JAIDS Journal of Acquired Immune Deficiency Syndromes, 2010. 53(2): p. 273-275.
9٫ Nasrollahzadeh, D., et al., Opium, tobacco, and alcohol use in relation to oesophageal squamous cell carcinoma in a high-risk area of Iran. British journal of cancer, 2008. 98(11): p. 1857-1863.
10٫ Masjedi, M.R., et al., Opium could be considered an independent risk factor for lung cancer: a case-control study. Respiration, 2012. 85(2): p. 112-118.
11٫ MacLennan, R.D.C., J Day, NE Law, CH Ng, YKm Shanmugaratnam, K, Risk factors for lung cancer in Singapore Chinese, a population with high female incidence rates. International Journal of Cancer, 1977. 20(6): p. 854-860.
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21٫ Mousavi, M.R.A., et al., Opium and risk of laryngeal cancer. The Laryngoscope, 2003. 113(11): p. 1939-1943.
22٫ Malekzadeh, M.M., et al., Opium Use and Risk of Mortality from Digestive Diseases: A Prospective Cohort Study. The American journal of gastroenterology, 2013. 108(11): p. 1757-1765.
23٫ Shakeri, R., et al., Opium: an emerging risk factor for gastric adenocarcinoma. International Journal of Cancer, 2013. 133(2): p. 455-461.
24٫ Naghibzadeh, T.A., et al., Opium as a Risk Factor for Upper Gastrointestinal Cancers: A Population-based Case-Control Study in Iran. Archives of Iranian medicine, 2014. 17(1): p. 2-6.
25٫ Ghadirian, P., et al., Oesophageal cancer studies in the Caspian littoral of Iran: some residual results, including opium use as a risk factor. International journal of cancer, 1985. 35(5): p. 593-597.
26٫ Shakeri, R., et al., Is opium a real risk factor for esophageal cancer or just a methodological artifact? Hospital and neighborhood controls in case-control studies. PloS one, 2012. 7(3): p. e32711.
27٫ Kamangar, F., et al., Opium use: an emerging risk factor for cancer? The Lancet Oncology, 2014. 15(2): p. e69-e77.
28٫ Hewer, T., et al., Ingested mutagens from opium and tobacco pyrolysis products and cancer of the oesophagus. The Lancet, 1978. 312(8088): p. 494-496.
29٫ Perry, P., et al., Induction of SCE by opium pyrolysates in CHO cells and human peripheral blood lymphocytes. Carcinogenesis, 1983. 4(2): p. 227-230.
30٫ Friesen, M., et al., Characterization and identification of 6 mutagens in opium pyrolysates implicated in oesophagel cancer in Iran. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1985. 150(1): p. 177-191.
|– Kerman Pr.||– Bahonar H.|
|– Afzalipoor H.|
|– Jawad Alaemah H.|
|– Shafa H.|
|– Fars Pr.||– Namazi H.|
|– Saadi H.|
|– Golestan Pr.||– Sayad Sh H.|
|– 5th Azar H.|
|– Tehran Pr.||– Imam Khomeini H.|
|– Masih Daneshvari H.|
|– Mazandaran Pr.||– Imam Khomeini H.|
|– Mashhad Pr.||– Imam Reza H.|
|– Hasheminejad H.|
|– Omid H.|
|– Kermanshah Pr.||– Ayatollah Taleghani H.|
|– Imam Khomeini H.|
|– Imam Reza H.|
MD, PhD Epidemiology
MD, PhD Epidemiology
MD, MPH ,Oncology
Elisabete Weiderpass Vainio
MD, PhD Epidemiology
MD, PhD, Epidemiology
Afarin Rahimi Movaghar
MD, PhD, Genetics
MD, PhD Clinical Epidemiology
MSc, Nutrition Science
Nutritional Status Investigator
Monireh Sadat Seyed Salehi
Job Exposure Analyst
Focal points in the study centers
MD, PhD, Epidemiology
MD, PhD, Epidemiology
Dr Farid Najafi
MD, PhD, Epidemiology
Researchers in the Study Centers
DVM, MPH, PhD Student
MD, MPH, PhD Student, Molecular Medicine
Ahmad Naghibzadeh Tahami
PhD Student, Epidemiology
Interviewer (Making data & biospecimens collection, preservation and distribution)
Vahid Gorganli Douji
It is hard to think about such a study in Iran without a large grant from government.
Fortunately after our application, NIMAD grant organization accepted to help us to reach our important objectives.
4 years_ Starting time, started in 2016