Role of opium in esophageal cancer: a hypothesis.

One of the highest areas of esophageal cancer incidence in the world is in northeastern Iran where up to 180 new cases/ 100,000 have been recorded per annum among Turkaman and Mazandarani villagers (10, 12). Although its use has been illegal in Iran since 1955, opium and its recycled pyrolytic product shireh are commonly smoked socially or are eaten for various bodily aches, diarrhea, and insomnia. There is now mounting evidence that the widespread use of such narcotics, particularly in the high-incidence regions, is associated with the development of esophageal cancer (5, 8, 20). One argument that has been put forward against the carcinogenicity of opium and its pyrolyzed products is that its rapid transit through the esophagus will not allow the potential carcinogen to act upon the mucosa (20). The association between opium usage and esophageal cancer in Iran was first noted during a 2-year clinical observation and case documentation by Dowlatshahi et al. (5) between 1974 and 1976, in which 61% of males and 25% of females among 126 patients with documented esophageal cancer gave a 5to 20year history of opium addiction antecedent to the onset of their symptoms. The sex ratio of the cancer incidence in this group was also 3:1. Brownish black particles of burnt opium were noted on the esophageal mucosa, and the odor of the compound was detected during endoscopie examination of these patients. During an endoscopie survey for early detection of esophageal carcinoma in an adjacent town, Crespi ef al. (3) reported 80% chronic esophagitis among 430 mainly asymptomatic adults. Informal local inquiry by one of the authors and epidemiological studies by the International Agency for Research on Cancer revealed a widespread habit of opium usage in the high-incidence esophageal cancer belt, as well as the presence of morphine metabolites in the urine of adults in this region (20). Hewer ef a/. (8) tested the mutagenicity of the pyrolyzed opium, a tarry residue collected from the pipe of addicts called sukhteh, and reported significant activity in Salmonella typhimurlum strains TA98 and TA100 in the presence of rat liver microsomes. This observation has now been substantially confirmed by International Agency for Research on Cancer investigators who pyrolyzed opium and its major alkaloid morphine under laboratory conditions closely mimicking the addict's pipe (12). It is suggested that heterocyclic