Stomach and Esophageal Cancers in Northern Iran
Stomach and Esophageal Cancers in Northern Iran
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.
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.
-  INCLUSION CRITERIA:

 Cases:

 Cases will be recruited and studied in Atrak Clinic, in Gonbad City.

 All patients referred to Atrak Clinic suspected to have EC.

 Patients 30 years of age or above from Gonbad, Minodasht, Kalaleh, Ramyan, Azad-Shahr,
 Maraveh-Tappeh, and the surrounding villages who have a histopathological diagnosis
 confirming ESCC and who consent to join the study will be enrolled as cases.

 Controls:

 Controls will be recruited into one of the four hospitals of the city (Shohada, Motahary,
 Khatam, and Borzouieh), and in major referral outpatient clinic (Taleghani Clinic).

 Controls will be selected from the patient 30 years of age or above who are referred to the
 four hospitals of the city and Taleghani Clinic.

 Only patients referred for certain diseases will be selected as controls.

 EXCLUSION CRITERIA:

 Controls:

 No association with tobacco or alcohol consumption, which are the main known risk factors
 for esophageal cancer (such as lung cancer, cardiovascular disease.

 Not causing major changes in diet or life-style for a long time (such as major GI diseases,
 chronic malignancies, diabetes).