Opium As a Risk Factor for Upper Gastrointestinal Cancers: a Population-Based Case-Control Study in Iran
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2SLXPDVD5LVN)DFWRUIRU8SSHU*DVWURLQWHVWLQDO&DQFHUV Original Article Opium as a Risk Factor for Upper Gastrointestinal Cancers: A Population-based Case-Control Study in Iran Ahmad Naghibzadeh Tahami MSc1,2, Narges Khanjani MD PhD3, Vahid Yazdi Feyzabadi PhD4,5, Masoomeh Varzandeh MD6, Ali- $NEDU+DJKGRRVW0'3K'7 Abstract 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 peo- ple (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. Keywords: Case-control, Iran, opium, risk factors, UGI neoplasms Cite this article as: Naghibzadeh Tahami A, Khanjani N, Yazdi Feyzabadi V, Varzandeh M, Haghdoost AA. Opium use as a risk factor for upper gastro-intestinal cancers: A population-based case control study in Iran. Arch Iran Med. 2014; 17(1): 2 – 6. Introduction world, with its northern parts especially Golestan province being one of the high-risk regions in the world.5–7 In Kerman province, GI cancers are among the most common cause of deaths in the largest province of Iran, located in the southeast of the country, U the world. Following lung cancer, gastric cancer has the GI cancers is also the most common cancers in recent years with second rank in the world in terms of mortality.1 The UGI an increasing trend; that is, among them, gastric cancer was the tract includes the oral cavity, esophagus, stomach, liver, and pan- most common form among men and the second most common creas.2 In Iran, these cancers are still considered as one of the most form among women.8 In addition, in recent years, the incidence of important cancers and cause of death. In recent years, cancer reg- liver cancer has increased in Iran. It should be also noted that the LVWU\¿QGLQJVLQ,UDQKDYHVKRZQWKDWPRUHWKDQSHUFHQWRI incidence of this cancer in Kerman is around three times higher deaths from cancer are attributable to UGI,3 with gastric cancer, than the national average.9 hepatic and bile duct cancers, and esophageal cancer having the Regular uses of opium have been recognized as a risk factor highest mortality rates among all other cancers.4 for many diseases including some cancers. Previous studies have Moreover, there is obvious geographic diversity in the incidence found some evidence about the association between opium use of UGI cancers in Iran. This shows that the risk factors for these and the risk of many cancers such as larynx, lung and bladder. 10–13 cancers are different in various parts of Iran. Iran is one of the Recently, a few studies have pointed to the association between countries where UGI cancers is higher than the other parts of the opium use, and esophageal and gastric cancer, but generally there LV OLWWOH HSLGHPLRORJLFDO ¿QGLQJV DERXW WKH DVVRFLDWLRQ EHWZHHQ $XWKRUV¶DI¿OLDWLRQV 1Research Center for Social Determinants of Health, In- opium use and UGI cancers.14–17 Nowadays, around 15 million stitute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran, 2Physiology Research Center, Kerman University of Medical Sci- people worldwide take opioids. Opium is traditionally used in ences, Kerman, Iran, 3Enviromental Health Research Center, School of Public many south-central Asian countries, especially Iran, Pakistan, Af- 4 Health, Kerman University of Medical Sciences, Kerman, Iran, Reseach Center ghanistan and India, as well as in some areas of South-East Asia.16 for Health Services Management, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran, 5Department of Health Manage- In Iran opioid use is more prevalent in the northern and southern ment and Economics, School of Public Health, Tehran University of Medical parts.18,19 In a study carried out in Golestan province (north of Iran Sciences, Tehran, Iran, 6Department of Forensic Medicine, School of Medicine, where the incidence of esophageal cancer is high) showed that 7 Tehran University of Medical Sciences, Tehran, Iran, Research Center for Mod- 16 eling in Health, Institute for Futures Studies in Health, Kerman University of 17 % of people aged more than 40 used opioids, and this might Medical Sciences, Kerman, Iran. contribute to the high rates of esophageal cancer in this area.14 In &RUUHVSRQGLQJDXWKRUDQGUHSULQWV Research Center for Modeling in Health, the north of Kerman the incidence of UGI cancers was relatively Institute for Futures Studies in Health, Kerman University of Medical Sciences, 8 Kerman, Iran. Address: Research Center for Modeling in Health, Kerman Uni- high; and opium consumption is the most common form of drug versity of Medical Sciences, Jahad Blvd, Ebn Sina Avenue, Kerman, Iran. abuse.18 It was found in a study in Kerman that the urine test of Tel: +98-341-2263787, Fax: +98-341-2263857, E-mail: [email protected]. 15 % of the subjects who were referred to one of the major Accepted for publication: 31 October 2013 2 Archives of Iranian Medicine, Volume 17, Number 1, January 2014 $1DJKLE]DGHK7DKDPL1.KDQMDQL9<D]GL)H\]DEDGLHWDO medical diagnostic laboratories was positive.19 1) teriak (raw opium), 2) shireh (opium sap), 3) sukhte (burned A cross-sectional study conducted in Golestan Province on the opium), 4) heroin. No subject was a sukhteh or heroin user. There- effect of opium use as a risk factor of esophageal cancer, found fore, for analysis we pooled two types of opium use (raw opium that men used opium more than women, and villagers more than and opium sap). Therefore, for analysis, we merged the use of all city dwellers; this may be related to the increased rate of esopha- types of opium together. geal cancer in men and villagers of this region.7 Dietary questionnaire included foodstuff used typically in the The high consumption of opium in Iran especially in Kerman, is Iranians diets especially in this region. All interviews were con- probably due to its adjacency to Afghanistan, the most important ducted at the interviewees’ houses and in a relaxing environment. opium producer in the world which facilitates the availability of If the subject was alive, interviews were mostly conducted face to opium. This fact in addition to the high incidence of UGI cancers, face; otherwise, the closest family member was interviewed. particularly in the northern parts of Kerman Province led us to This study was approved by the Ethical Committee of Kerman design a case-control study to explore the possible association be- University of Medical Sciences. Interviews were conducted after tween opium use and the incidence of UGI cancers. taking a verbal informed consent from subjects or their relatives. Materials and Methods Statistical analysis For each exposure (tobacco and opium), the cumulative con- Selection of subjects and controls sumption (average daily use multiplied by the duration of use) In this matched case-control study, 142 patients with UGI can- was calculated, and divided into three subgroups of non-use, low cers (oral cavity, liver, esophagus, stomach, or pancreas) were XVH PHGLDQXVHLQWKHFRQWUROV DQGKLJKXVH !PHGLDQXVHLQ selected from the northern part of Kerman based on the pathologi- the controls). Since median use in controls probably represented cal data records at the cancer registry of Kerman province from the consumption in the entire population, it was considered as the August 2010 to November 2012. Hospital-based information was FXWRIISRLQWIRUFODVVL¿FDWLRQRIWKHDPRXQWRIFRQVXPSWLRQ,QDOO also re-checked to ensure that all eligible patients were detected. analyses, the non-use group was set as the reference group. In order to calculate the sample size, the following assumptions In this study, some subjects started using opioids after the diag- were set: the minimum desired odds ratio of 2, the frequency of nosis of cancer. Thus, to minimize the effect of reverse causality, opium use in the general population 0.2, the ratio of numbers only records of opioid use prior to the disease diagnosis were re- of control per case 2 : 1, the statistical power and the alpha error corded. Because of the low incidence of alcohol use, it was classi- 0.8 and 0.05 respectively. Using these assumptions, a minimum ¿HGLQWRWZRJURXSVZLWKDQGZLWKRXWWKHKLVWRU\RIFRQVXPSWLRQ sample size of 150 was calculated. However, since almost all of subjects were Muslim, the alcohol The patients’ information including the home address, the phone use was very low. number and type of cancer were extracted from their medical records. In this analysis, three outcomes were modeled 1- all cancers, A date was set with cases or their close relatives in advance 2- gastric cancer, and 3- The other cancers (oral cavity, liver, pan- via their phone numbers. For every subject, two neighborhood creas and esophagus). As compared with the other high enough controls were selected, matched in terms of gender and age.