Cohort Profile: The Golestan Cohort Study--a prospective study of oesophageal cancer in northern Iran

Abstract

The earliest reports of high incidence of oesophageal cancer (OC) in the northern parts of Iran date back to the early 1970s.1,2 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 OC in the eastern portion of the Caspian Sea littoral, in the area that 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, with estimated incidence rates of 109/105 among men and 174/105 among women (adjusted to the 1970 World Standard Population).3 The registry also showed low incidence of OC in the nearby Gilan province, 300 km to the west of Golestan, with incidence rates of 15/105 and 5.5/105 among men and women, respectively. A series of studies were conducted in the region in the 1970s, but they were not conclusive in explaining the very high rates. However, they pointed to several factors, including: (i) a diet deficient in fruits and vegetables;4 (ii) low socio-economic status; (iii) thermal injury from consumption of very hot tea;5 and (iv) carcinogen exposure from lifestyle factors including opium consumption.6–8 The high incidence of OC in Golestan was confirmed by a recent screening study.9 Aetiological 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.10 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 logistics of establishing a prospective study in Golestan. The aims of the pilot study were to assess the response rate of the study population, to develop valid and reliable methods for assessing nutritional, anthropometric and life-style factors, to develop follow-up methods to ascertain mortality and cancer incidence among the enrolled subjects, and to establish efficient procedures for collecting and storing biological samples. Results of the pilot study confirmed the feasibility of conducting a prospective cohort study in Golestan.11,12 Subsequently, the Golestan Cohort Study (GCS) was launched in January 2004. This study is part of a series of investigations into the etiology of upper gastrointestinal cancers in this area, collectively named Gastric and Oesophageal Malignancies in Northern Iran (GEMINI). 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. The primary aims of the GCS are: To identify risk factors for OC by a comprehensive assessment of ethnicity, occupational history, socio-economic status, past medical history, family history of cancers, gastrointestinal symptoms and signs, tobacco, opium and alcohol use, oral health, anthropometric characteristics, physical activity and tea drinking habits, including tea temperature. Nutritional patterns are also evaluated using a food frequency questionnaire (FFQ) specifically developed for this population and validated during the pilot study.12 The FFQ covers 116 food items, including bread and cereals, meat and dairy products, oils, sweets, legumes, vegetables, fruits and condiments, as well as cooking methods. To establish biospecimen banks for blood, urine, hair and nail samples to be used in molecular and genetic studies of cross-sectional or nested case–control design. To provide a model for population-based studies in a country in economic and social transition based on collaboration between local health workers, local health authorities, national research centres, national government and international research institutions. The study population is a sample of the Golestan population, aged 40–75 years. The primary goal was to establish a cohort of 50 000 healthy individuals, with equal numbers of men and women, 20% from urban areas and 80% of Turkmen ethnicity. We enrolled the urban participants from Gonbad City, the second largest city of Golestan, with 126 797 inhabitants (28 102 aged 40–75), and the rural participants from villages in Gonbad, Kalaleh and Aq-Qala counties (Figure 1), with 347 683 inhabitants (53 121 aged 40–75). Geographic location of Golestan province in northern Iran. The dashed area approximately corresponds to the GCS field A total of 16 599 urban inhabitants older than 40 years were selected randomly from five areas of Gonbad City by systematic clustering based on household number. The selected inhabitants were contacted at home by specially trained health workers and invited to visit the Golestan Cohort Study Center, a research centre specifically established for this project in Go