This case-control study is evaluating environmental and genetic risk factors for esophageal squamous cell carcinoma (ESCC) in Golestan Province, Iran. Age standardized ESCC incidence rates of 109/100,000 in men and 175/100,000 in women were reported from this area in the 1970s, and no studies have been performed since that time. Atrak Clinic, a referral clinic for upper gastrointestinal diseases, was recently established in Golestan Province by physicians from the Digestive Diseases Research Center of Tehran University of Medical Sciences, and this Clinic serves as the field center for this study. All patients referred to the Clinic routinely undergo upper endoscopy and biopsy for evaluation and diagnosis. Patients who have histologically confirmed ESCC and consent to join the study have been enrolled as cases. Two control groups have also been enrolled in this study, one selected from the neighborhoods of case subjects (primary controls) and one from the patients referred to Atrak Clinic who do not have cancer (secondary controls). Both the cases and the controls were interviewed and underwent collection of biological specimens including blood, hair and nails. After a 3 1/2 year accrual period (2003-2007) 300 cases, 571 neighborhood controls and 300 Atrak Clinic controls were successfuly enrolled and are currently being analyzed. Environmental risk factors (including life-style, habits, and nutritional status) are being assessed through questionnaires and objective measurements in biological specimens. The role of genetic polymorphisms is also being studied using genomic DNA from cases and controls. Biopsy samples collected from cases and clinic controls are also being used to evaluate the association of esophageal PAH exposure and case status.