Stomach and Esophageal Cancers in Northern Iran
Condition: Esophageal Cancer
MeSH terms: Esophageal Neoplasms
Study type: Observational

Summary: 
      This study, sponsored jointly by the National Cancer Institute and the Tehran University of
      Medical Sciences, will explore the causes of cancers of the stomach and esophagus (the tube
      that runs between the mouth and the stomach) in Northern Iran. This is a unique area of study
      for the following reasons:

        -  Some of the highest rates of esophageal cancer in the world have been reported in
           northeastern Iran 109 cases per 100,000 men and 175 cases per 100,000 women each year
           about 40 times higher than the rates of this cancer in the United States.

        -  In this area of Iran, unlike most areas of the world, the disease affects more women
           than men.

        -  Within 300 miles along the southern border of the Caspian Sea, the rates fall to 10
           cases per 100,000 people per year.

      The high rates of disease in this area, the unique geographic distribution of cases, and the
      exceptionally high rate in women make Northern Iran a promising site for studying esophageal
      and stomach cancers.

      Patients 30 years of age and older who are referred to the upper gastrointestinal disease
      Atrak Clinic in Gonbad, Golestan Province, Iran, with suspected esophageal cancer may be
      eligible for this study. In addition, control subjects 30 years of age and older with certain
      specified diseases will be recruited from patients referred to four hospitals in Gonbad and
      to the Taleghani Clinic. After giving informed consent, all participants will undergo the
      following procedures:

        -  Interviews, including questions about age, ethnicity, education, and other demographic
           data; habits, such as tobacco, opium, and alcohol consumption; personal and family
           medical history; diet, with special attention to food preservation, cooking methods, and
           drinking water; physical activity; occupational and residential history; body
           measurements; signs and symptoms of upper gastrointestinal disease; oral hygiene; animal
           contact; transfusion history; and family socioeconomic status.

        -  Blood draw (15 milliliters, or 1 tablespoon) for genetic and chemical testing for
           markers that may predict who gets the disease.

        -  Hair and nail sampling to identify minerals or compounds whose exposure may be related
           to esophageal cancer.

        -  Endoscopy to evaluate the health of the esophagus and stomach. This test will be
           performed on all case patients and on control participants who give their permission.
           Before the examination, the subject will swallow a liquid that numbs the throat and may
           be given a medicine through a vein to promote drowsiness. The subject will then swallow
           a tube (endoscope) through which the doctor can look at the esophagus and stomach and
           take samples of tissue to look for disease. The tissue samples will be examined
           microscopically and will then be stored for possible future genetic or other testing
           related to diagnosing or determining the risk of esophageal cancer.
    

Detailed description: 
      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.
    

Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Patients who have histologically confirmed esophageal squamous cell carcinoma of the
        esophagus and consent to join the study were enrolled as cases. There were 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
        served as the primary control group.
      
Biospecimen description: 
      Blood, hair, nails
    
Keywords: Esophageal Cancer; Case-Control Study; Environmental Risk Factors; Genetic Risk Factors