The rising incidence of thyroid cancer over the past 3 decades has been attributed to incidentally discovered thyroid nodules, demographic variables, and/or environmental impacts. Additional known risk factors associated with an increased risk of thyroid cancer include family history of the disease, radiation exposure, Hashimoto’s thyroiditis, and elevated thyroid-stimulating hormone (TSH). Obesity, race, and socioeconomic factors also contribute to higher advanced thyroid cancer rates. Despite our increased understanding of thyroid cancer risk factors, collectively, they do not fully explain why the incidence rates are rising worldwide.

California has a very diverse population with a wide range of races and ethnicities, as well as a broad variety of international immigrants. Geographically, the state of California also has diverse topography and is comprised of large areas of coastline, mountainous regions, valleys, vast expanses of desert or arid land, as well as a plethora of agricultural areas scattered throughout the state. It also has one of the largest collections of decommissioned nuclear reactors in the country. Other than the known impact of ionizing radiation on the development of thyroid cancer, only a few studies have addressed other possible environmental exposures as contributing factors to the rise in thyroid cancer incidence.

This area of research has been difficult to study, due to the geographic mobility of many area residents and the difficulty in collecting exposure data. However, there are some studies that have emerged, suggesting exposure to environmental chemicals might increase the risk of thyroid cancer. A link between environmental toxins/pesticides and thyroid cancer has been suggested, but no study large enough to assess that implication has yet been conducted. High urinary levels of the metal tungsten have also been associated with elevated TSH levels, which in turn could increase one’s risk of thyroid cancer. Also, an individual’s likelihood of being exposed to any of these—or other&mdash;environmental risk factors could vary with geographical location.

In our tertiary referral center, we have noted an unusually high rate of advanced thyroid cancers presenting from across the state of California. To investigate the possibility of environmental impacts as a predisposition for thyroid cancer, we sought to identify counties in California with possible geographic clustering of advanced thyroid cancer cases. We recently published our findings in the 

A total of 26,983 patients with newly diagnosed thyroid cancer from 1999 to 2008 were reviewed from the California Cancer Registry (CCR) and the Office of Statewide Health Planning and Development Registry. Established in 1947, the CCR is California’s statewide population-based cancer surveillance system and is one of the largest, most comprehensive cancer registries in the world. It captures information on every patient who is newly diagnosed with cancer in the state and follows his or her progress forward. It has collected detailed information on over 3.4 million cases of cancer, and more than 162,000 new cases are added annually.

Advanced thyroid cancer rates were calculated within each county—defined as those with distant metastatic stage, regional and/or distant metastatic stage (RM), as well as those with well-differentiated thyroid cancer (WDTC) diagnosed before age 30. National averages were taken from Surveillance Epidemiology and End Results (SEER) data. For our outcome, we used the stage of disease at presentation rather than the rising cancer incidence within each county. This was chosen because incidence rates of thyroid cancer are rising throughout the state, the country, and the world.

When we looked at our own counties, each one had an increased incidence over the course of the previous 10 years. The rate of increase was not different from what is already known for the rest of the country and in other parts of the world. Our interest was more about how delayed the cancers were being diagnosed, since that significantly impacts patient care, morbidity, and mortality.

Presenting with more advanced disease carries greater lifetime risks for patients with thyroid cancer. Regional disease in patients with thyroid cancer includes cancers with direct extension and/or those involved with lymph node metastases. These stages carry a higher risk of treatment morbidity related to recurrent laryngeal nerve injury, hypoparathyroidism, and injury to nearby organs, such as the trachea and esophagus. Regional stages also carry a higher rate of recurrence, which requires additional surgery and further morbidity related to increased surgical risks of dissections within a scarred neck.

Studies suggest that there is also a higher rate of mortality in these patients as compared with those without regional disease. Regional disease in WDTC also often requires subsequent systemic treatment with radioactive iodine (RAI), which may need to be given more than once if the cancer is particularly aggressive in its recurrence. Distant metastatic disease in thyroid cancer obviously carries a much higher rate of mortality. It requires not only surgical but systemic therapy, as well with either RAI and/or chemotherapy. Additionally, quality of life is severely impacted in all patients with metastatic thyroid cancer related to the widespread disease within the lungs, liver, and bones, as well as side effects related to systemic therapies.

Our results showed that there was no obvious clustering of advanced cases within certain regions in California; however, on average, the entire state of California had significantly higher rates of distant metastatic thyroid cancer (6.73%) and RM (34.92%) than the national Surveillance, Epidemiology, and End Results Program (SEER) averages (4%, 29% respectively, 

 <.001). Of the 47 California counties, 20 had significantly higher percentages of distant metastatic thyroid cancer than the national SEER average (range 6%-13% vs 4%,

 <.05), and 20 had a higher percentage of RM than the national SEER average (range 35%-48% vs 29%, 

 <.05). Two California counties had higher rates of young patients with WDTC (range 14.29%-17.9%) than the national SEER average (12%).

When comparing those counties with a combination of more regional plus distant metastatic disease (RM) than the national average to those counties who had equal or less disease, there was also no difference in age, sex, comorbidity, or histology distribution. Those counties with more RM disease also had proportionally more minority patients (African American, Hispanic, and Asian-Pacific Islander) and patients with higher socioeconomic status. Those counties with more RM disease also had more patients with private insurance and patients who were more likely to be treated at academic institutions.

Despite the lack of obvious clustering of advanced cases in any one part of the state, we were surprised to find that almost the entire state of California had such high numbers of patients presenting with advanced disease. The reasons for these proportional differences are not clear, but they warrant further investigations as they have high impact on a patient’s morbidity, mortality, quality of life, medical costs, and treatments required over the course of a lifetime.

Understanding the demographic and geographic variance of advanced thyroid cancer in California is vital to develop interventions that may decrease exposures or increase access to care at earlier stages. Our data suggest that access to care, living remotely, and more aggressive histologies cannot fully explain the increased rates of advanced disease. The data suggest that there might be other external exposures in California contributing to the rise of advanced disease.

Environmental impacts on thyroid cancer have not been extensively studied—other than ionizing radiation&mdash;due to the difficulty of obtaining the data necessary to prove any causative risk factor. Our group is currently analyzing data and is currently investigating the effects of pesticide use on thyroid cancer, although that may not be the only impact on disease progression. Other potential risk factors such as radiation exposure due to decommissioned nuclear reactors or radon, air pollution, etc., should also be investigated.

Articles

To investigate the possibility of environmental impacts as a predisposition for thyroid cancer, researchers sought to identify counties in California with possible geographic clustering of advanced thyroid cancer cases.

Avital Harari, MD

Articles

Researchers Investigate Increased Incidence of Thyroid Cancer in California