An Ecological Study of the Association between Opiate Use and Incidence of Cancers

Document Type : Original Article(s)


1 PhD Student, Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

2 Associate Professor, Cancer Research Center, Institute of Cancer, Tehran University of Medical Sciences, Tehran, Iran

3 Professor, Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, Maryland, USA

4 Professor, Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran

5 Professor, Regional Knowledge Hub, and WHO Collaborating Centre for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran


Background: Cancer is the second leading cause of death after cardiovascular disease. In recent years it has been hypothesized that opiate use could be a risk factor for cancer. This study aimed to evaluate a possible association between opiate use and common cancers using ecological statistics from around the world.Methods: To investigate the association we used ordinary linear regression models. The log10-transformed age-standardized incidence rate (ASR) of cancers was used as dependent variables in the models. We adjusted for smoking, alcohol use per capita, human development index (HDI), and body mass index (BMI) as confounding variables. We extracted these variables from different data sources including the GLOBOCAN 2012, the United Nations Office on Drugs and Crime (UNODC) annual reports, World Health Organization database, the United Nations Development Program (UNDP) report 2012, and published literature. We estimated two separate models for each cancer, one for males and the other for both sexes.Findings: Opiate prevalence ranged from 0.01% to 2.65% and its median was 0.20%. In the multiple regression models for both sexes, opiate use was significantly associated with bladder (β = 0.59), kidney (β = 0.16), oral cavity (β = 0.27), esophagus (β = 0.33), larynx (β = 0.17) and other pharynx (β = 0.36) cancers. In the models based on the male data, the coefficient and the significances were approximately the same for the above cancers but larynx cancer was no longer significantly associated with opiate use.Conclusion: There was a significant association between opiate use and risk of cancers. We suggest that more studies should be conducted, especially in high-risk areas of the world.


  1. United Nations Office on Drugs and Crime. World drug report 2011. New York, NY: United Nations Publications; 2011.
  2. Camilleri M. Opioid-induced constipation: Challenges and therapeutic opportunities. Am J Gastroenterol 2011; 106(5): 835-42.
  3. Kamangar F, Shakeri R, Malekzadeh R, Islami F. Opium use: an emerging risk factor for cancer? Lancet Oncol 2014; 15(2): e69-e77.
  4. Perry PE, Thomson EJ, Vijayalaxmi, Evans HJ, Day NE, Bartsch H. Induction of SCE by opium pyrolysates in CHO cells and human peripheral blood lymphocytes. Carcinogenesis 1983; 4(2): 227-30.
  5. Friesen M, O'Neill IK, Malaveille C, Garren L, Hautefeuille A, Cabral JR, et al. Characterization and identification of 6 mutagens in opium pyrolysates implicated in oesophageal cancer in Iran. Mutat Res 1985; 150(1-2): 177-91.
  6. Malaveille C, Friesen M, Camus AM, Garren L, Hautefeuille A, Bereziat JC, et al. Mutagens produced by the pyrolysis of opium and its alkaloids as possible risk factors in cancer of the bladder and oesophagus. Carcinogenesis 1982; 3(5): 577-85.
  7. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136(5): E359-E386.
  8. Ng M, Freeman MK, Fleming TD, Robinson M, Dwyer-Lindgren L, Thomson B, et al. Smoking prevalence and cigarette consumption in 187 countries, 1980-2012. JAMA 2014; 311(2): 183-92.
  9. World Health Organization. Global health observatory (GHO) data [Online]. [cited 2016]; Available from: URL:
  10. United Nations Development Programme. Human development index (HDI) [Online]. [cited 2016]; Available from: URL:
  11. Najafipour H, Masoomi M, Shahesmaeili A, Haghdoost AA, Afshari M, Nasri HR, et al. Effects of opium consumption on coronary artery disease risk factors and oral health: Results of Kerman Coronary Artery Disease Risk factors Study a population-based survey on 5900 subjects aged 15-75 years. Int J Prev Med 2015; 6: 42.
  12. Sharifi V, Amin-Esmaeili M, Hajebi A, Motevalian A, Radgoodarzi R, Hefazi M, et al. Twelve-month prevalence and correlates of psychiatric disorders in Iran: the Iranian Mental Health Survey, 2011. Arch Iran Med 2015; 18(2): 76-84.
  13. Singh GK, Azuine RE, Siahpush M. Global inequalities in cervical cancer incidence and mortality are linked to deprivation, low socioeconomic status, and human development. Int J MCH AIDS 2012; 1(1): 17-30.
  14. Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol 2012; 13(8): 790-801.
  15. Patel AR, Prasad SM, Shih YC, Eggener SE. The association of the human development index with global kidney cancer incidence and mortality. J Urol 2012; 187(6): 1978-83.
  16. Yan TL, Hu QD, Zhang Q, Li YM, Liang TB. National rates of Helicobacter pylori recurrence are significantly and inversely correlated with human development index. Aliment Pharmacol Ther 2013; 37(10): 963-8.
  17. Sasco AJ, Secretan MB, Straif K. Tobacco smoking and cancer: A brief review of recent epidemiological evidence. Lung Cancer 2004; 45(Suppl 2): S3-S9.
  18. Gandini S, Botteri E, Iodice S, Boniol M, Lowenfels AB, Maisonneuve P, et al. Tobacco smoking and cancer: a meta-analysis. Int J Cancer 2008; 122(1): 155-64.
  19. Lagergren J, Bergstrom R, Lindgren A, Nyren O. The role of tobacco, snuff and alcohol use in the aetiology of cancer of the oesophagus and gastric cardia. Int J Cancer 2000; 85(3): 340-6.
  20. Moghaddam AA, Woodward M, Huxley R. Obesity and risk of colorectal cancer: A meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol Biomarkers Prev 2007; 16(12): 2533-47.
  21. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008; 371(9612): 569-78.
  22. Arnold M, Pandeya N, Byrnes G, Renehan AG, Stevens GA, Ezzati M, et al. Global burden of cancer attributable to high body-mass index in 2012: a population-based study. Lancet Oncol 2015; 16(1): 36-46.
  23. Fedirko V, Tramacere I, Bagnardi V, Rota M, Scotti L, Islami F, et al. Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies. Ann Oncol 2011; 22(9): 1958-72.
  24. Shakhssalim N, Hosseini SY, Basiri A, Eshrati B, Mazaheri M, Soleimanirahbar A. Prominent bladder cancer risk factors in Iran. Asian Pac J Cancer Prev 2010; 11(3): 601-6.
  25. Ketabchi A, Gharaei M, Ahmadinejad M, Meershekari T. Evaluation of bladder cancer in opium addicted patients in the Kerman Province, Iran, from 1999 to 2003. J Res Med Sci 2005; 10(6): 355-7.
  26. Khademi H, Malekzadeh R, Pourshams A, Jafari E, Salahi R, Semnani S, et al. Opium use and mortality in Golestan Cohort Study: prospective cohort study of 50,000 adults in Iran. BMJ 2012; 344: e2502.
  27. Verhamme KM, Sturkenboom MC, Stricker BH, Bosch R. Drug-induced urinary retention: incidence, management and prevention. Drug Saf 2008; 31(5): 373-88.
  28. Vassou D, Notas G, Hatzoglou A, Castanas E, Kampa M. Opioids increase bladder cancer cell migration via bradykinin B2 receptors. Int J Oncol 2011; 39(3): 697-707.
  29. Atici S, Cinel I, Cinel L, Doruk N, Eskandari G, Oral U. Liver and kidney toxicity in chronic use of opioids: an experimental long term treatment model. J Biosci 2005; 30(2): 245-52.
  30. Naghibzadeh Tahami A, Khanjani N, Yazdi Feyzabadi V, Varzandeh M, Haghdoost AA. Opium as a risk factor for upper gastrointestinal cancers: a population-based case-control study in Iran. Arch Iran Med 2014; 17(1): 2-6.
  31. Wigmore T, Farquhar-Smith P. Opioids and cancer: friend or foe? Curr Opin Support Palliat Care 2016; 10(2): 109-18.
  32. Sacerdote P. Opioids and the immune system. Palliat Med 2006; 20(Suppl 1): s9-15.
  33. Robinson PG, Acquah S, Gibson B. Drug users: oral health-related attitudes and behaviours. Br Dent J 2005; 198(4): 219-24, discussion.
  34. McGrath C, Chan B. Oral health sensations associated with illicit drug abuse. Br Dent J 2005; 198(3): 159-62.
  35. Liu Q, Yan L, Xu C, Gu A, Zhao P, Jiang ZY. Increased incidence of head and neck cancer in liver transplant recipients: a meta-analysis. BMC Cancer 2014; 14: 776.
  36. Rosenstein DI. Effect of long-term addiction to heroin on oral tissues. J Public Health Dent 1975; 35(2): 118-22.
  37. van Leeuwen MT, Grulich AE, McDonald SP, McCredie MR, Amin J, Stewart JH, et al. Immunosuppression and other risk factors for lip cancer after kidney transplantation. Cancer Epidemiol Biomarkers Prev 2009; 18(2): 561-9.
  38. Shakeri R, Malekzadeh R, Etemadi A, Nasrollahzadeh D, Aghcheli K, Sotoudeh M, et al. Opium: an emerging risk factor for gastric adenocarcinoma. Int J Cancer 2013; 133(2): 455-61.
  39. Malekzadeh MM, Khademi H, Pourshams A, Etemadi A, Poustchi H, Bagheri M, et al. Opium use and risk of mortality from digestive diseases: a prospective cohort study. Am J Gastroenterol 2013; 108(11): 1757-65.
  40. Pappagallo M. Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surg 2001; 182(5A Suppl): 11S-8S.
  41. Tuteja AK, Biskupiak J, Stoddard GJ, Lipman AG. Opioid-induced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain. Neurogastroenterol Motil 2010; 22(4): 424-30, e96.
  42. Wang C, Yuan Y, Hunt RH. Helicobacter pylori infection and Barrett's esophagus: A systematic review and meta-analysis. Am J Gastroenterol 2009; 104(2): 492-500.
  43. Mousavi MR, Damghani MA, Haghdoust AA, Khamesipour A. Opium and risk of laryngeal cancer. Laryngoscope 2003; 113(11): 1939-43.
  44. Khoo R. Radiotherapy of carcinoma of the Larynx. Ann Acad Med Singapore 1981; 10(3): 307-10.
  45. Kurz A, Sessler DI. Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. Drugs 2003; 63(7): 649-71.
  46. Greenwood-Van Meerveld B, Gardner CJ, Little PJ, Hicks GA, Dehaven-Hudkins DL. Preclinical studies of opioids and opioid antagonists on gastrointestinal function. Neurogastroenterol Motil 2004; 16 Suppl 2: 46-53.
  47. Sadjadi A, Derakhshan MH, Yazdanbod A, Boreiri M, Parsaeian M, Babaei M, et al. Neglected role of hookah and opium in gastric carcinogenesis: a cohort study on risk factors and attributable fractions. Int J Cancer 2014; 134(1): 181-8.
  48. Shakeri R, Kamangar F, Mohamadnejad M, Tabrizi R, Zamani F, Mohamadkhani A, et al. Opium use, cigarette smoking, and alcohol consumption in relation to pancreatic cancer. Medicine (Baltimore) 2016; 95(28): e3922.
  49. Masjedi MR, Naghan PA, Taslimi S, Yousefifard M, Ebrahimi SM, Khosravi A, et al. Opium could be considered an independent risk factor for lung cancer: A case-control study. Respiration 2013; 85(2): 112-8.
  50. MacLennan R, Da Costa J, Day NE, Law CH, Ng YK, Shanmugaratnam K. Risk factors for lung cancer in Singapore Chinese, a population with high female incidence rates. Int J Cancer 1977; 20(6): 854-60.