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Pathways to Discovery: Winter 2014

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Thyroid Cancer Research:  A Storied Past and Promising Future at the University of Chicago

At first glance, it may seem ironic that the same institution that gave the world the first nuclear self-sustaining chain reaction also made the first link between radiation exposure and thyroid cancer. The former is a well-known story written by Enrico Fermi on a squash court under the west stands of old Stagg Field at the University of Chicago in 1942. The latter, however, is less familiar but shaped the field of thyroid cancer etiology and management, and profoundly changed how radiation from X-rays and other sources was used throughout medicine and society. This rich history has laid the foundation for the innovative approaches and groundbreaking science developed by researchers at the University of Chicago Medicine Comprehensive Cancer Center (UCCCC). Through these efforts, they are tackling the growing clinical challenges of thyroid cancer.

Radiation Exposure: An Unchecked Risk
As early as before World War I, radiation was promoted as a cure-all for a multitude of diseases and benign ailments––from acne to tonsils and adenoids and enlarged thymus. Initially, there was little concern about the medical consequences of radiation exposure. The long-term medical effects that were recognized following the atom bomb blasts at Hiroshima and Nagasaki at the end of World War II raised public concern about the harmful consequences of radiation exposure, even low-dose exposure. However, it was a study led by Dr. Dwight Clark, professor of surgery at the University of Chicago, in 1955 that showed that low-dose radiation used in medical practice could have harmful results, and first proposed that papillary cancers of the thyroid were caused by radiation. Additional papers from University of Chicago investigators strengthened the association between radiation exposure and thyroid cancer in adults, as well as in children.

By the late 1960’s, tighter controls on radiation use were implemented, but patients who had received low-dose radiation to their head or neck as children continued to be treated for thyroid cancer as adults. Edwin Kaplan, MD, professor of surgery, came to the University of Chicago Medicine in 1971 and joined Drs. Leslie DeGroot and Samuel Refetoff to address this “Chicago Endemic.” Their studies identified many patients who had received low-dose radiation to their neck as children and were found to have thyroid cancer as young adults. These reports led to considerable public anxiety and attention. Large recall programs for at-risk patients were conducted across the Midwest. An analysis of 5,300 children who had received low-dose radiation to their head and neck at Michael Reese Hospital showed that 10 percent of these children later developed thyroid cancer.

As the research epicenter, the University of Chicago even hosted a National Institutes of Health-funded symposium on radiation-induced thyroid cancer in 1976. The University of Chicago research team continued to contribute significantly to this field well into the 1990s, including showing that radiation-induced thyroid cancer was not more aggressive than other thyroid cancers, as originally thought.

Rates on the Rise
Although the era of the “Chicago Endemic” has long passed, and while most other cancers have decreased in incidence, thyroid cancer rates have risen dramatically in the past few decades––6% to 8% per year, especially in women. Recent work by Raymon Grogan, MD, assistant professor of surgery; Brian Chiu, PhD, associate professor of health studies; Ya-Chen Tina Shih, PhD, associate professor of medicine; and Dr. Kaplan, as well as Briseis Aschebrook-Kilfoy, PhD, research associate in health studies, projects that papillary thyroid cancer will double in incidence by 2019 and become the third most common cancer in women of all ages after breast and lung cancer. Unfortunately, the lack of funding and attention to thyroid cancer nationally means that research has lagged behind efforts made in most other cancers.

Current Research Efforts Under Way
Dr. Grogan and his research team, including Dr. Kaplan, Roy Weiss, MD, chief of endocrinology, and Sharone Kaplan, recently took a closer look at the University of Chicago cohort with an unprecedented median follow-up of 27 years. They found that lifetime recurrence rates for papillary thyroid cancer were 28%, and 11% of recurrences and 17% of deaths from papillary thyroid cancer occurred 20 years or more after the original diagnoses. These data inform how thyroid cancer survivors are monitored and support life-long surveillance of these patients.

Such research also highlights the need to elucidate the molecular basis of primary thyroid cancer, as well as causes of recurrence and metastasis, and how risk factors such as unknown environmental exposures are contributing to these rising thyroid cancer rates. Current research efforts include genetic studies by Dr. Grogan’s group in collaboration with Kenan Onel, MD, PhD, associate professor of pediatrics, and Habibul Ahsan, MD, Louis Block Professor of Health Studies, to identify mutations in thyroid cancer specimens to uncover the molecular drivers of cancer and DNA variants that affect the risk of developing thyroid cancer after low-level radiation exposure. These research avenues create optimism that, despite the growing incidence and healthcare burden associated with thyroid cancer, advances in prevention, management, and treatment are emerging.

Drs. Kaplan and Grogan agree that “there is still a great deal of work to do.”

 

Ernst Lengyel

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