The high prevalence of esophageal cancer in the province of Golestan during the 1970's attracted the attention of many international researchers, and based on this, a team of international scientists in collaboration with researchers from the School of Public Health and Institute of Nutrition from Tehran University of Medical Sciences (TUMS) came together and began their studies at this site in Iran. This research group was led by Professor Nick Day from the International Agency for Research on Cancer (IARC) where he played a critical role, however, this 8-year research remained incomplete as a result of the political unrests which led to the Islamic Revolution in Iran.
The reports from the Cancer Registry of the International Agency for Research on Cancer of the The World Health Organization (IARC / WHO) at the time reported the prevalence of esophageal cancer to be 165 cases per 100,000 men and 195 out of 100,000 for women in Northern Iran
Esophageal cancer belt in Northern Iran
The prevalence of esophageal cancer in Northern Iran is one of the highest for cancer incidence in a given region of the world, and for this reason, the Northeastern region of Iran is globally recognized as one of the regions with the highest incidence of a particular type of cancer (esophageal) in worldwide, which is frequently noted in medical books.
The efforts of the international research team with Dr. Nick Day’s leadership along with collaborators at the School of Public Health and the and Nutrition Institute of TUMS culminated in a number of case – control and ecological studies, the results of which were eventually published in internationally recognized journals. However, these studies, following political developments which led to the Islamic Revolution in Iran remained incomplete. Consequently, during these years researchers were only able to propose a few hypotheses about the possible causes for the high prevalence of esophageal cancer in Northeastern Iran.
After the international scientific team’s research which was led by Dr. Nick Day from the International Agency for Research on Cancer of the The World Health Organization (IARC / WHO) remained incomplete, Dr Farrokh Saeedi, a professor from Shahid Beheshti University of Medical Sciences (SBUMS), with assistance from his young research team, in particular Dr. Saman Fahimi, Dr. Alireza Sepehr and Dr. Mohammad-Jafar Farahvash conducted a new study during 1993-1996 in the Bandar Turkaman area which focused on the causes for the high prevalence of esophageal and gastric cancer in Northern Iran. This study is also considered as one of the subfields of the main Golestan Cohort Study.
The Administrative Team for the Pilot Project of the Golestan Cohort Study
Dr. Malekzadeh and a number of administrative team members for the main Golestan Cohort Study in Gonbad
Subsequently, in 1997, Dr. Malekzadeh, a distinguished professor of Tehran University of Medical Sciences and head of the Digestive Diseases Research Institute at the University, along with a team of 50 experienced researchers in medical sciences from Tehran and Golestan, in collaboration with the International Agency for Research on Cancer of the World Health Organization (IARC / WHO), the US National Cancer Institute (NCI / NIH), the Cancer Research UK Cambridge Institute (CRUK CI), Johns Hopkins University from the US, and Karolinska Institute of Sweden began the Golestan Cohort Study with the aim of identifying the causes for the high prevalence of esophageal cancer in northeastern Iran, centered in the city of Gonbad-e-Kavus, with a pilot study including 1,057 individuals
Dr. Malekzadeh's conversation with Ayatollah Nourmofidy, the Supreme Leader’s representative in Golestan province, when visiting Atrak Clinic
Top image: Dr. Malekzadeh visiting the Cancer Research Center in China before launching the main cohort study in Iran
Bottom image: noting the list of participants in the esophageal cancer study of 1969 by the International Agency for Research on Cancer in Lyon, France
Participants at the Gastric and Esophageal Cancer Congress in Tehran and Gastrointestinal Cancer Conference in China
Dr. Malekzadeh meeting Dr. Donald Maxwell (Max) Parkin in order to plan a cancer registry system
Dr. Malekzadeh began preliminary analyses for the implementation of the pilot study three years prior to this phase in 1994, following a series of meetings and discussions with political and social authorities in the province of Golestan, as well as religious leaders and provincial authorities to secure their assistance and support for the implementation of the study. Visiting other cancer research centers in the world, including the Cancer Research Center in China, regular consultation with the WHO’s IARC, holding seminars at the Cancer Research Agency as well as important scientific conferences with the presence of world renowned and experienced researchers in the field of esophageal and gastric cancers in Iran in addition to establishing a cancer registry system for gastric cancer in Ardabil and esophageal cancer in Golestan are among some of Dr. Malekzade's preparatory efforts for conducting this cohort study.
Beginning the Golestan Cohort Study
Subsequently, in 2007, through selection of a large team of national researchers, the main cohort study of Golestan was launched with more than 50,000 samples based on indicators such as age, sex, tobacco and alcohol consumption, literacy and income level and followed up for a period of 15 years. Prior to the implementation of this study, a case-control study was conducted in 2004 by the DDRI of TUMS; the results of which were published in the British Journal of Cancer (BJC). Later a case-control study of esophageal and gastric cancer was carried out at the Advanced Subspecialty Clinic of Atrak which was established for the purpose of conducting the Golestan cohort study and the results of this study were published in some of the most credible journals worldwide, where drinking hot tea, non- potable water, opium consumption, Helicobacter pylori infection, smoking, poor oral and dental health, lack of vegetables and fruits in an individual’s diet, poverty and illiteracy, genetic predisposition and family history were noted as seven risk factors for esophageal cancer.
Establishment of the Advanced Subspecialty Clinic of Atrak at Khatam-ol-Anbia Hospital in the Province of Golestan for Conduct the Study
Dr. Pourshams, an active member of the Golestan Cohort Study along with a group of residents from Gonbad
Preparations for the implementation of the main study were provided simultaneous to the pilot study and the large-scale prospective study on cancer in the province of Golestan was conducted with a focus on the city of Gonbad. Several provincial meetings were held to help make the necessary preparations for the implementation of this large study, and ultimately, the main cohort study of Golestan began in 2007 on 50,000 individuals between the ages of 40-75. Participants included residents from 333 villages (rural areas) from Gonbad-Kavus, Kalaleh and Agh-Qala, as well as 10,000 residents from the inner-city areas of Gonbad, who were randomly selected from all five urban areas of the city.
Blood, urine, hair and nail samples were collected from the study participants; the nutrition questionnaire was completed, and the amount of tea consumption was recorded for each individual while the temperature of the beverage was measured and documented. Individuals were also subject to regular examinations predetermined for the study. One month following implementation of the study, 80 refrigerators were installed at the Cohort Study Center, and all samples were transferred from the Atrak Clinic to the Center. Due to the risk of the samples being damaged in a natural disaster or other events, the specimens were placed in to two categories, and a portion of these samples was transferred from Gonbad to Tehran, and later to the IARC headquarters in Lyon, France along with an epidemiologist from the Agency who had come for a inspection visit at the study site in Iran.
All study participants were given a membership card and followed up once after a 12-month period by phone. Meanwhile, the databases at the Atrak Clinic and the Cancer Registry Center in Golestan Province were investigated to identify any cancer cases in the study participants. Given the trends of this study so far, it is anticipated that the follow-up process will continue for up to 30 years. Also, training sessions to recruit more specialist physicians for collaboration in the study at the cities of Gonbad, Kalaleh and Agh-Qala have been held monthly during the years since the beginning of this study by Dr. Reza Malekzadeh, where they have been provided with the necessary trainings.
In this vast and unprecedented study in Iran, in addition to support from government officials, the health care center of Golestan, the public health networks in the cities of Gonbad, Kalaleh and Aqqala, as well as the unassailable contributions of Dr. Shahriar Semnani, the Chancellor of Golestan University of Medical Sciences – who played a very effective role in supporting this study – we witnessed the cooperation of international centers, including the International Agency for Research on Cancer (IARC), the Cambridge Cancer Research Center (CRUK), etc. through the provision of financial and scientific resources to help implement, organize and register cancer cases, and provide specialized services.
Achievements and Accomplishments of the Golestan Cohort Study Pertinent to Cancer
The Golestan Cohort Study attained important achievements in the field of cancers, including cancers of the upper gastrointestinal system, and in particular, esophageal cancer:
Demonstrated and globally documented the effect of drinking hot beverages on the development of esophageal cancer
Providing evidence to support "the impact of drinking hot beverages on the development of esophageal cancer" is another major achievement of the Cohort Study of Golestan, which is one of the regions with the highest incidence of esophageal cancer in the world. This finding has also been registered by the International Agency for Research on Cancer (IARC).
This study, which was conducted on more than 50,000 individuals, demonstrated that drinking hot beverages is a primary risk factor for causing esophageal cancer, and that the odds of developing esophageal cancer is 10 times higher in those who drink their tea 2-3 minutes after serving it compared to those who drink it after 4-5 minutes.
Drinking hot tea causes penetration of more carcinogenic substances into the esophagus, which increases the probability of developing cancer.
In this study, the temperature of the tea consumed by participants was measured. The analyses showed that 39% of subjects consumed their tea with a temperature of less than 60 degrees Celsius, 38.9% consumed their tea with a temperature of 60- 64 degrees, while 22% at a temperature of 65 degrees and higher. Drinking hot tea has proven to be an important contributing factor to the prevalence of esophageal cancer in the Northeastern region of Iran.
“Demonstrated that opium use is a determinant factor in causing cancer for the first time in the world”, its Global Registration and Receiving a Recognition Medal from the International Agency for Research on Cancer (IARC)
The large Cohort Study of Golestan, for the first time in the world, proved that the consumption of opium definitely causes various types of cancer, including cancers of the esophagus, larynx, lung, stomach, pancreas and bladder.
Analysis of the survey results and follow-up of 50,455 individuals participating in the Golestan Cohort Study, 17% of whom comprised of 8,467 individuals reporting regular consumption of opium (7,126 of whom have expired to date), demonstrated that opium use is associated with an increased risk of death due to all causes of mortality, particularly ischemic heart disease and various types of cancers.
This achievement from the Golestan Cohort Study is particularly significant as the world faces a lack of accurate studies regarding the “long-term consumption” of opioid drugs and its effects on cardiovascular diseases and various types of cancer, especially since most recently published studies in this area have been retrospective case studies. Meanwhile, the large Cohort Study in the Northeast of Iran (Golestan) which has the highest percentage of opium users and incidence of esophageal cancer in the world, is the only study that provides accurate and reliable information on a large number of individuals (in the general population, not a specific population ) who have been consuming opiod compounds over long term.
This major achievement of the large Cohort Study of Golestan led to being awarded the achievement medal by the International Agency for Research on Cancer (IARC) under the leadership of Professor Reza Malekzadeh, which was also registered / recorded under “Opium as a Carcinogen" in the Global Registration List by the IARC.
Including the Iranian Cancer Report in the global reference of "Cancer Incidence in Five Continents" for the first time
Preparing the cancer registry report for the population in the province of Golestan in 2003 was one of the prerequisites for the Golestan Cohort Study, which became the first official report on the state of cancer in Iran to enter the global reference "Cancer Incidence in Five Continents", and with continuation of the cancer registry program during implementation of the Cohort Study, additional cancer registry centers have been established in other provinces of Iran.
The formation of a modern biobank with the purpose of early diagnosis and identification of risk factors for diseases
With the implementation of the large Cohort Study of Golestan, a modern and comprehensive biobank, including biological samples of more than 50,000 individuals from the study participants, was developed for the purpose of more effective diagnosis and treatment of diseases. In addition to helping researchers identify disease risk factors, the biobank will also help reduce the incidence of diseases and their treatment cost for the Iranian Health Care System.
Achievements of the Golestan Cohort Study Pertinent to Other Chronic Diseases
The 10 Important Causes of Premature Deaths in Iran
The outcomes and achievements of the Golestan Cohort Study were never limited to cancer. It was also a starting point and an unprecedented opportunity to explore other chronic non-communicable diseases, and the results of each long-term study would provide a response to important questions for the Iranian Health Care System, while reducing the burden of chronic diseases.
Non-communicable diseases currently account for 80% of the disease burden in the country. Ischemic heart diseases, stroke, road accidents, hypertension, Alzheimer's disease, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, other cardiovascular diseases and gastric cancer are considered to be among the NCDs and 10 most important causes of morbidity and mortality in Iran.
Through assessment and evaluation of chronic diseases such as cardiovascular, hypertension, renal, liver diseases, etc the Golestan Cohort Study has discovered important applicable information which has resulted in the development of Polypill for heart attack and stroke prophylaxis, as well as Sovodak for the treatment of Hepatitis C. This study has also provided valuable data relevant to other chronic diseases, part of which has been used in international studies such as the Global Burden of Disease (GBD) project.
Helping to produce science in Iran And educating scientists
The Golestan cohort study has achieved all its predetermined objectives, and in addition to providing scientific evidence for the prevention of chronic non-communicable diseases, in particular gastrointestinal cancer, heart attack, stroke, as well as renal and hepatic failure, it has also provided suitable opportunities for applicable research and an appropriate model for conducting large-scale interventional research projects. Furthermore, while educating and training young scientists and preserving the specialized workforce in the country,
the Golestan Cohort Study has also contributed to the discovery and development of scientific information, pulled in research funding from major scientific research centers in the world, provided 30 free educational opportunities for young researchers, and published 120 articles from the Golestan Cohort Study in prestigious international journals.