Thyroid Cancer Working Group

In 2007, the DCEG Senior Advisory Group established a series of working groups to enable strategic planning in areas that are central to the Division's research. Some of the groups focus on specific tumors that are highly lethal or rising in incidence. Toward that end, a working group was established to plan studies of thyroid cancer, whose incidence rates have increased about 6 percent per year over the past decade. The increase in thyroid cancer has been greater among women than men, such that thyroid cancer is now the seventh most common female cancer. These upward trends are not limited to localized tumors, suggesting that the increasing rates cannot be explained entirely by improvements in detection.

The Thyroid Cancer Working Group was created to foster strategic collaborations in several areas of research, including descriptive epidemiology, environmental and radiation exposures, lifestyle and nutritional exposures, molecular tumor markers, pathway-based candidate gene studies, and genome-wide association studies (GWAS). Since the group was established nearly one year ago, almost 20 manuscripts related to thyroid cancer have been submitted for publication, with many more in progress. Areas of research concentration undertaken by members of the DCEG Thyroid Cancer Working Group are listed in the box at the end of the article.

Cochaired by Elaine Ron, Ph.D., and Alice J. Sigurdson, Ph.D., both of the Radiation Epidemiology Branch (REB), the working group includes scientists from DCEG, the Center for Cancer Research (CCR), and the extramural community. Recent observations from descriptive epidemiology studies in the United States have clarified temporal, gender, racial, and age patterns by cell type and size (see Figure 1).

Internationally, the incidence rates vary widely by country, but they have generally increased—except in Sweden, where, surprisingly, the rates for men and women have decreased. In age-period-cohort analyses, birth cohort and time period effects have contributed to the rising incidence in the United States, suggesting that surveillance and screening have improved, although lifestyle and environmental exposures may be responsible as well. Briseis Kilfoy, Ph.D., and Mary H. Ward, Ph.D., both of the Occupational and Environmental Epidemiology Branch, along with William F. Anderson, M.D., M.P.H., and Susan S. Devesa, Ph.D., both of the Biostatistics Branch (BB), conducted these descriptive analyses.

Lifestyle and body mass index (BMI) were investigated in two cohorts. A major finding was the association of high BMI with excess risk of papillary and follicular thyroid cancers, with risks up to 1.7-fold in the highest level of adiposity. Consistent with previous findings, a reduced risk of thyroid cancer was associated with smoking and alcohol consumption. DCEG investigators involved in this research have included Amy Berrington de González, D.Phil., Alina V. Brenner, M.D., Ph.D., and Cari Meinhold, M.H.S., all of REB, as well as Yikyung Park, Sc.D., of the Nutritional Epidemiology Branch (NEB). In addition, Drs. Kilfoy and Ward found in the Iowa Women's Cohort an increased risk of thyroid cancer associated with higher nitrate levels in public water supplies and with intake of dietary nitrate.

External ionizing radiation is one of the few established risk factors for thyroid cancer, but much less is known about the effects of exposure to radioiodines. Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, Ethel S. Gilbert, Ph.D. (REB), and colleagues have analyzed thyroid cancer incidence rates for counties according to the estimated level of radioactive fallout from atmospheric tests conducted in Nevada during the 1950s. Counter to expectation, this ecologic analysis confirmed an earlier finding of excess risk associated with exposure occurring before the age of 1, but not for exposure occurring between ages 1 and 15. Despite the uncertainties in dose estimation and case ascertainment due to migration, the study somewhat supports the role of radioactive fallout in the rising incidence of thyroid cancer. The findings are noteworthy because radioiodines have been linked to thyroid cancer and benign thyroid nodules in DCEG-led studies of populations exposed to nuclear weapons testing in Kazakhstan, the Chornobyl accident in Ukraine, and emissions from the Mayak nuclear weapons plant in Russia. Most recently, Maureen C. Hatch, Ph.D. (REB), along with Drs. Brenner and Ron, analyzed thyroid cancer occurrence in children who were exposed in utero to radioiodine from the Chornobyl accident and found an elevated risk, suggesting the need for caution in the medical use of radioiodine among pregnant women.

Ongoing projects for the Thyroid Cancer Working Group include the identification of molecular and genetic biomarkers of thyroid cancer (including tumors that are radiation related) and studies on the impact of various chemicals (including persistent organochlorines), the effects of nitrate and nitrite in drinking water and food, and the role of dietary and nutritional factors. Racial-linkage studies are also under way to evaluate associations with various medical conditions, including other cancers. Because thyroid cancer is relatively rare, DCEG investigators are collaborating with extramural colleagues to conduct pooled studies of several cohorts to increase statistical power.

Other members of the working group include Dr. Sanjeeve Balasubramaniam (CCR); Dr. Parveen Bhatti of the Fred Hutchinson Cancer Research Center; Dr. Florent De Vathaire of the Institute for Health and Medical Research (INSERM); Dr. Lindsey Enewold of the U.S. Military Cancer Institute; Joseph F. Fraumeni, Jr., M.D., Division Director; Jay H. Lubin, Ph.D. (BB); Kiyohiko Mabuchi, Ph.D., and Gila Neta, Ph.D. (both of REB); Ruth M. Pfeiffer, Ph.D. (BB); Rachael Stolzenberg-Solomon, Ph.D., M.P.H., R.D. (NEB); Margaret A. Tucker, M.D., Director of the Human Genetics Program and Chief of the Genetic Epidemiology Branch; and Lene Veiga, Ph.D. (REB).

—Alice Sigurdson, Ph.D., and Elaine Ron, Ph.D.

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