The incidence of thyroid cancer was 45 times greater among those who received the highest radiation dose as compared to those in the lowest-dose group, according to a team of American and Russian researchers led by Scott Davis, Ph.D., and colleagues at Fred Hutchinson Cancer Research Center. They report their findings in the September issue of Radiation Research.

"This is the first study of its kind to establish a dose-response relationship between radiation dose from Chernobyl and thyroid cancer," said Davis, referring to the observation that as radiation doses increase, so does the risk of thyroid cancer. "We found a significant increased risk of thyroid cancer among people exposed as children to radiation from Chernobyl, and that the risk increased as a function of radiation dose."

Having such information in hand, Davis said, may help officials better predict what long-term health effects to expect in the event of a similar nuclear accident or terrorist attack.

"Another potential benefit of the findings is that it allows officials to more accurately understand and document the magnitude of the thyroid-cancer burden that has resulted from Chernobyl. This information will be important in designing and maintaining programs targeted toward the victims of the disaster."

While about 30 people were killed immediately from the blast, which remains the worst accident of its kind in history, an estimated 5 million people were exposed to the resulting radiation.

"Prior to Chernobyl, thyroid cancer in children was practically nonexistent. Today we see dozens and dozens of cases a year in the regions contaminated by the disaster, and the incidence continues to rise," Davis said. "This provides some evidence that there's an excess of thyroid cancer in children and in people who were children at the time of the accident. However until now nobody had taken the next step to find out just how much a risk there is and whether it rises along with radiation dose."

While previous Chernobyl studies have relied on broad-stroke estimates of radiation exposure based on such factors as ground contamination, geographic proximity to the northern Ukraine plant or other surrogate measures of exposure, this study is the first of its kind to factor into the equation individualized estimates of radiation dose based on in-person interviews about diet and other lifestyle factors, said Davis, a member of Fred Hutchinson's Public Health Sciences Division.

"After all these years, many efforts have been made by various research groups around the world to study the health effects of Chernobyl, and hundreds of scientific papers have been published. But ours is the first report that provides quantitative estimates of thyroid-cancer risk in relation to individual estimates of radiation dose," said Davis, also chairman of the Department of Epidemiology at the University of Washington School of Public Health and Community Medicine in Seattle.

Kenneth Kopecky, Ph.D., a biostatistician in Fred Hutchinson's Public Health Sciences Division, was the study's co-investigator and directed the data analysis. Public Health Sciences Division staff managed and coordinated all aspects of the project. They included Theresa Taggart (project manager), Lynn Onstad (statistician), Teri Kopp (administration) and Laurie Shields (research coordinator).

The Fred Hutchinson team organized a collaborative effort with a dozen scientists at four Russian institutions to conduct this research: the Medical Radiological Research Center (in Obninsk), the Byransk Diagnostic Center and the Bryansk Institute of Pathology (both in Bryansk), and the National Center of Hematology (in Moscow). All investigators were members of the International Consortium for Research on the Health Effects of Radiation funded by the U.S. Office of Naval Research.

The researchers focused their efforts on western part of the Bryansk Oblast of Russia. This region, located about 66 miles northeast of Chernobyl, is the most heavily contaminated area in the Russian Federation. This was the first study of this type among residents of the Russian Federation exposed to Chernobyl radiation.

Working through a local cancer registry, the researchers identified 26 people with thyroid cancer who were less than 20 years old when the Chernobyl accident occurred; the majority were under 16 when their thyroid cancers were diagnosed. They then identified 52 healthy control subjects from the general population for comparison purposes. The controls and cancer cases were matched by age and place of residence at the time of the accident.

The researchers then set about collecting information from these individuals and their mothers or fathers that would allow them to estimate each person's radiation dose using computer models. Interviews took place in the home and were conducted by Russian physicians. Individual doses depended largely on the ingestion patterns of food contaminated with radioactive iodine-131 (I-131), which concentrates in the thyroid gland. The primary source of food-based I-131 was milk from cows that grazed on contaminated pastures. Radiation doses to the thyroid increased along with the amount of milk and dairy products consumed. External, airborne radiation and contamination of other foods also contributed somewhat to the overall dose, depending on the person's proximity to the plant at the time of the accident. These doses were all received within the first few months after the accident, before the I-131 in the environment decayed into non-radioactive elements. While other radioactive contaminants remain in the area, they do not cause appreciable doses of radiation to the thyroid.

In addition to the study's ability to estimate individual radiation doses based on personal interviews, other strengths of the study included the fact that all cases of thyroid cancer were confirmed independently by a panel of expert pathologists, and the study focused on people exposed as young children and adolescents, a group that is likely to be most susceptible to the effects of radiation exposure to the thyroid gland. Limitations of the study included its small sample size and its reliance on individual recall for reporting factors such as milk-consumption patterns that were used to estimate radiation dose.

Efforts are under way to investigate a larger population in a similar fashion to see if these findings can be replicated, Davis said. For his contributions to the field, earlier this year Davis became the first foreign epidemiologist elected to the Russian Academy of Medical Sciences. The group's status in that country is on a par with the esteemed National Academy of Sciences in the United States. In May he received an honorary diploma in Moscow.

Davis and colleagues have extended their cancer-risk studies to older Chernobyl survivors and are investigating how the damage caused to DNA by radiation influences the risk of developing thyroid cancer.

This work is part of Fred Hutchinson's Global Health Initiative, which focuses on international collaboration to understand and solve some of the most widespread health problems in the world, including cancer and infectious diseases.

SIDEBAR

IT ALL STARTED WITH A RUSSIAN HELICOPTER PILOT WHO WAS TREATED FOR LEUKEMIA AT FRED HUTCHINSON

Providing some long-awaited answers to Chernobyl survivors has been a rewarding research endeavor for Scott Davis, Ph.D., and colleagues at Fred Hutchinson Cancer Research Center, but it hasn't been a straightforward one.

Some of the team's greatest achievements were simply establishing the working relationships and infrastructure to get the studies off the ground.

"Within the first year of the 1986 accident, we were very interested in seeing if we could get involved and participate in long-term studies of health effects," Davis said. "But at the time of the accident, our government and that of the former Soviet Union were not so friendly, so establishing connections through that route didn't work."

But in 1990, an opportunity surfaced when a Russian helicopter pilot involved in the initial efforts to contain the Chernobyl radiation developed leukemia and came to Fred Hutchinson for a bone-marrow transplant. After his treatment, an informal exchange program began between Fred Hutchinson and the National Center for Hematology in Moscow, whose director approached the center for assistance in developing a research and treatment institute for victims of the accident. Davis and colleague Kenneth Kopecky, Ph.D., made their first trip to Moscow that year.

Then, in 1992, the Soviet Union collapsed. "We were back to square one in terms of negotiations," Davis said.

But, thanks to efforts by Fred Hutchinson's then-president and director, Robert W. Day, M.D., and by the late Adm. Elmo Zumwalt, a former center trustee and former chief of naval operations for the U.S. Navy, new relationships were established. In 1992, a research consortium consisting of three international teams working in Russia, Belarus and Ukraine was created to study long-term health effects of the radiation released at Chernobyl.

"Our initial work in Russia was simply to conduct small pilot studies to establish in concrete terms whether we could carry out all phases of an epidemiological study," Davis said. "There was no history of doing this kind of research in Russia or the other two countries. We had to set it all up from scratch."

Challenges included purchasing Russian vehicles for the field teams using federal dollars – an unprecedented bureaucratic challenge for the researchers – importing all laboratory equipment and supplies, and then figuring out a way to maintain them without the standard resources that one takes for granted in the United States.

"It's been a long haul and an enormous amount of time and work," Davis said, whose 30-plus trips to the former Soviet Union include walking the grounds of the evacuated plant and surveying the desolated 30-kilometer evacuation zone.

Once the team established the capability to do the research, the group began its studies of thyroid cancer, a disease linked to radiation exposure. By the early 1990s, many new cases of the disease, particularly among young children, were diagnosed in regions near the blast. Since then, reports show several hundred cases of thyroid cancer in young children in the three countries contaminated by Chernobyl, a trend that appears to be continuing.

Despite the lack of resources available to initiate these studies, Davis said that scientists and citizens of the three countries were eager for the research from the start. "Our collaborators in Russia have been terrific colleagues," he said. "We now have very close ties with our partner institutions."

He also credited the strong encouragement and support from Fred Hutchinson's senior administration for helping him establish stable working relationships with their overseas colleagues.

"The incredible support and flexibility of the center, especially in the early stages, really made this happen. That can't be overstated," Davis said.

Fred Hutchinson Cancer Research Center, home of two Nobel laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Fred Hutchinson receives more funding from the National Institutes of Health than any other independent U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson, in collaboration with its clinical and research partners, the University of Washington Academic Medical Center and Children's Hospital and Regional Medical Center, is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 38 nationwide.