Exploring the role of environmental nitrate exposure in the increasing incidence of thyroid cancer

During the past several decades an increasing incidence of thyroid cancer has been observed in several countries including the United States. The factors responsible for the rapid increase in incidence have been unknown. Though some have argued that the increase in thyroid cancer incidence is an artifact of improvements in diagnosis and screening technology, a consequence of increased detection, evidence of increases in large tumors in addition to small tumors has suggested otherwise. The first paper in this dissertation project assesses global trends in thyroid cancer incidence to confer an understanding of the global disease burden, changes in international rates over the past decades, and a country-level comparison to generate causal hypotheses. The international incidence trends are assessed using the IARC Cancer Incidence in Five Continents (CIV) Database (volume 9). The second paper focuses on trends in the United States using a comparative age-period-cohort analysis to investigate the notable gender disparity using the SEER 9-Registry Database. Following the descriptive projects, an environmental epidemiology approach is taken as investigation into the role of the environment in thyroid cancer risk has been largely limited to the effect of radiation exposure. Nitrate and nitrite in the diet and in contaminated drinking water are specifically assessed due to the increasing evidence of the adverse effect of these chemicals on thyroid function, thyroid disease, and potentially cancer. The impact of elevated nitrate and nitrite in the diet is evaluated in the NIH-AARP cohort and nitrate contaminated drinking water is evaluated in the Old Order Amish study population. As the IARC CIV Report, the SEER 9-Registries, and the NIH-HARP Diet and Heath cohort represent some of the premier resources available for epidemiologic research, the results from each project confer strong evidence of the hypotheses of interest. As such, the characterization of thyroid cancer incidence and the investigation of the role of nitrate and nitrite in this dissertation project make a novel contribution to the literature and enhances the discourse on a cancer which is increasingly becoming a public health problem.