The earliest reports of high incidence of esophageal cancer (EC) in the northern parts of Iran date back ‎to the early 1970s. A population-based cancer registry was established in 1969 as a joint effort between ‎Tehran University and the International Agency for Research on Cancer (IARC). This registry confirmed ‎the high incidence of EC in the eastern portion of the Caspian Sea littoral, in the area which is now ‎known as Golestan Province. The highest incidence rates were reported from the semi-desert plain ‎settled mainly by people of Turkmen ethnicity in Gonbad and Kalaleh counties. A series of studies were ‎conducted in the region in the 1970s, but they were not conclusive in explaining the very high rates. ‎Etiological hypotheses related to diet and life style can be best addressed in prospective cohort studies, ‎in which measurement error can be reduced and recall bias is minimal. From 2002 to 2003, a pilot study ‎of 1057 subjects was conducted by the Digestive Disease Research Center (DDRC) of Tehran University ‎of Medical Sciences in collaboration with IARC and the US National Cancer Institute (NCI) to evaluate the ‎logistical aspects of establishing a prospective study in Golestan. Subsequently, the Golestan Cohort ‎Study (GCS) was launched in January 2004. The study protocol and the informed consent used for this ‎study were approved by the ethical review committees of DDRC, IARC, and NCI. In June 2008, the ‎accrual goal of 50 000 subjects was reached and enrollment was closed. ‎