Stomach and Esophageal Cancers in Northern Iran

This case-control study (the first phase of the GEMINI project) is primarily focused on exploring the etiology (etiologies) of squamous cell carcinoma of the esophagus in northern Iran.

Esophageal and gastric cancers, together, are responsible for more than 1,000,000 annual deaths in the world. In 1996, cancers of the stomach and esophagus ranked first and second respectively, among the most frequent cancers in Iran, excluding skin cancers. Some of the highest incidence rates for esophageal cancer in the world have been reported in Northeastern Iran, in Northern Gonbad, with Age Standardized Rates (ASR) of 109/100,000 in men and 175/100,000 in women (1). These rates are approximately 40 times higher than those seen in the US. In this area, unlike most areas of the world, the incidence is higher in women than in men. Additionally, within 300 miles along the southern border of Caspian Sea, the rates fall to 10/100,000. The highest rates of EC in the world, a unique geographical distribution of cases, and an exceptionally high rate among women all make Northern Iran a very intriguing site for studying this disease.

An upper-GI referral clinic (Atrak Clinic) has already been established in Gonbad, Golestan Province, and DDRC researchers have conducted feasibility studies in this clinic. For the case-control study, local internists and other health system workers will refer suspected cases of esophageal cancer to the Clinic. All such patients will undergo endoscopy and biopsy for ascertainment of diagnosis. Patients who have histologically confirmed esophageal squamous cell carcinoma of the esophagus and consent to join the study will be enrolled as cases. There will be two control groups in this study, one selected from the neighborhood of case subjects and one from the patients referred to Atrak Clinic who do not have cancer. The neighborhood control group will serve as the primary control group. Both the cases and the controls will be interviewed and undergo collection of biological specimens including blood, hair and nails. Free (and optional) endoscopy will also be offered to the neighborhood controls. A four-year accrual of 300 cases, 600 neighborhood controls and 300 clinic controls is expected.

Environmental risk factors (including life-style, habits, and nutritional status) will be assessed through questionnaires and objective measurements in biological specimens. The role of genetic polymorphisms will be studies using genomic DNA from cases and controls. A subset of samples collected from cases and controls will be used to evaluate gene expression patterns, using microarray analysis, differences in serum protein patterns, using SELDI analysis.