Parvian Ghadirian had been in London studying for his Ph.D. when the Islamic Revolution erupted in February of 1979. Ghadirian said he knew that he had to return to Iran. He said he had to view the remains of the Westernized cancer registry that he operated in the small northern Iranian city of Babol.
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Though Ghadirian said he eventually left Iran with most of the registry data, the loss of the Babol facility symbolized the end of a decade-long quest to explain the extremely high rate of esophageal cancer in areas of northern Iran. Or, as some Western scientists believed, a golden opportunity had slipped away to identify the environmental causes of this poorly understood disease.
But, the golden opportunity may now have returned. In the early 1990s, or shortly after Irans marathon war with Iraq, scientists in Tehran formed their own society to study esophageal cancer, and they even secured a small pot of scarce government research money.
This led last November to the publication of the first updated rates of esophageal cancer from Iran in nearly 30 years. The scientists say additional studies are in the works and note that, with American political sanctions possibly softening against the pro-reform Iranian government, future collaborations with the technologically advanced West could be a boon for discovering important genes and polymorphisms involved in the disease.
Cancer Belt
Iran sits at the far western end of Central Asias notorious "Esophageal Cancer Belt,"an area that stretches eastward from Iran through Turkmenistan, northern Afghanistan, Uzbekistan, and Kazakhstan into northern China and Mongolia. All of these countries have near epidemic rates of the disease, with scientists estimating that residents have a 20-fold greater chance of developing esophageal cancer than those living elsewhere in the world.
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In the mid 1960s, an international team of scientists set their sights on a narrow, 400-mile stretch of land in northern Iran, pinched between the Caspian Sea to the north and the Elburz Mountain Range to the south. Unlike most other regions within the Esophageal Cancer Belt, the land here is ecologically diverse, featuring green mountain forests, sandy beaches, and a parched, bone-dry desert. The scientists wondered, what if there are sharp differences in the number of people with esophageal cancer in the desert versus the mountain region? Would this allow them to focus on the high-incidence areas and single out possible environmental clues?
Their hunch proved correct. Reporting in Science in 1972, Kmet and Mahboubi discovered that in the humid, high-rainfall area beneath the slopes of the Elburz Mountains, the disease is relatively uncommon. But, to the east of the Caspian Sea, in the low-precipitation desert area, the incidence seemed to be extremely high.
In 1973, Mahboubi et al. confirmed the Science paper with 3-year data from the newly established Babol cancer registry. In men, the data showed the age-adjusted rate in the eastern desert area might be as high as 165.5 per 100,000; while in the western, heavy-rainfall area, the rate might be as low as 13.0 per 100,000. For women, the rates were 165.5 in the eastern region and 2.3 in the western area. Interestingly, the authors found that for other types of cancer, there was a uniform incidence throughout the region.
The scientists then turned their attention to a seminomadic tribe that resides in the rural desert region called the Turkomen. Originally from northern China and once among the fiercest marauders of central Asia, many Turkomen seemed in previous studies to be especially prone to esophageal cancer.
This was doubly interesting because only a small percentage of Turkomen smoke tobacco or drink alcohol, the standard risk factors for esophageal cancer in the industrialized nations.
Because Turkomen live elsewhere within the cancer belt, such as Turkmenistan and Afghanistan, and also tend to marry from within their extended families, some suspected a possible genetic link, then an unpopular idea in cancer research.
Subsequent work, led by Ghadirian, who said he spent more than 3 years living in the same felt tents and wearing the same traditional garb as the Turkomen, identified several possible risk factors: consuming a diet low in animal protein, fruits, and vegetables; eating bread contaminated with sharp seeds and silica; swallowing residue from smoking opium; and gulping down exceedingly hot tea.
"I think the average temperature of the tea was 70 degrees centigrade," said Ghadirian. "You cannot even touch it. Because water is very expensive, they just drink to kill their thirst. They believe that if you are thirsty and you drink very hot tea, you will be all right."
But, in 1979, the Islamic Revolution erupted in Iran. A year later brought the Iraqi War, forcing the Iranian government to ration food and spend nearly half of its revenue by the mid-1980s on the import of weapons.
Along the Caspian Sea, the tumor registry in ruins, research on esophageal cancer ground to an immediate halt. That is where the story remained for the next 20 years, a golden opportunity frozen in time.
But the ice began to thaw with the end of the war in August 1990. According to Farrokh Saidi, M.D., an internationally known thoracic surgeon at Shaheed Beheshti University School of Medicine in Tehran, he and a few of his colleagues just began talking. "It started off with a few of us meeting to discuss the issue of esophageal cancer, a disease which all members of our informally organized group felt was almost a public health problem," he said, noting that the group later adopted its current name of the Iranian Society for the Study of Esophageal Cancer, or ISSEC.
"We reviewed the pertinent literature on the subject," he said. "Then, after considerable thought, we felt that the most practical approach would be to embark on a survey in a part of the country that had been reported to be a high-risk area some years ago."
That would be the Turkoman Plain. Reporting last November in the British Journal of Cancer, Saidi et al. confirmed the now 27-year-old report that esophageal cancer is common. The study, in which nearly 4,200 asymptomatic Turkoman adults aged 30 and older were screened for cancerous lesions of the esophagus, identified 253 people with possible abnormalities. The screening was performed with Chinese-type balloon cytology tubes, a noninvasive probe to detect early esophageal cancer.
Of the 183 people who agreed to further examination, the scientists reported detecting three likely cancers. Saidi et al. also later contacted local health officials for information on any Turkoman who had sought treatment for esophageal cancer during the year. After a painstaking search, they tallied 14 patientsof which 13 were Turkomen. Within 2 years, all but two had died.
Based on these 14 patients and their high death rate, the authors estimated that the age-standardized rate for clinically advanced esophageal cancer in the region is 144.1 per 100,000 for men and 48.8 per 100,000 for women. In 1997, in the United States, the incidence was 6.4 among men and 1.8 among women.
"There is a very, very strong suggestion that there is a genetic background," said Ghadirian, reflecting on his previous work in the region. "Environmentally, we didnt find anything, except dietary deficiencies and eating opium dross. But living next to the Turkomen are a lot of other ethnic groups. They are there, almost in the same area. But cancer of the esophagus among them is not even one-tenth of that in the Turkoman."
Alireza Sepehr, a leader of the Turkoman study and a scientist at Massieh Daneshvari Hospital in Tehran, noted that ISSEC is now busy conducting a similar study of esophageal cancer in the western Caspian city of Ardebil, which has a large Azerbaijani population. Sepehr said he and his colleagues have also collaborated with scientists from the International Agency for Research on Cancer to search for genetic alterations in esophageal tumors from Iranian patients.
"The ultimate aim is to map out the incidence of esophageal cancer, and perhaps also cancer of the stomach, for the whole country," said Saidi. "Equally important to us is to establish cancer registries in different parts of Iran. One is already functional at the University of Tehran, and the second will soon be operational in Ardebil."
Despite limited research funds and Irans continued political isolation, Saidi said he is optimistic about the future. He said IARC continues to be helpful to ISSEC, and Sepehr noted that he will arrive in the United States this month to begin a research fellowship at the National Cancer Institute.
Though the Turkoman region is remote, requiring a sometimes treacherous 8-hour train ride from Tehran over the Elburz Mountains, Ghadirian, too, said he remains enthusiastic about the scientific opportunities of the region. "I worked there for 15 years. I know every corner of that area. So, I still have interest, if it is possible to find the cause of this disease."
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