Population-based big data analysis and institution-specific data verification of secondary cancer risk according to thyroid cancer in patients with lipid metabolic disease

Abstract

Lipid metabolism diseases, such as non-alcoholic fatty liver disease and dyslipidemia, are continuously increasing due to lifestyle changes, and many studies have reported that the incidence of other cancers increases in these diseases. Thyroid cancer occurs frequently, and its prognosis is good; therefore, there are many survivors. Lipid metabolic diseases and thyroid cancer are recognized for their association with high-lipid states and obesity. In the author’s previous study, dyslipidemia was found to increase the risk of secondary cancer in patients with thyroid cancer, and there are many obesity-related secondary carcinomas. In this study, we aimed to confirm whether thyroid cancer itself affects the risk of secondary cancer in patients with lipid metabolic disease and the factors affecting this risk through analysis of institutional data and big data from the Korea National Health Insurance system. In both institutional and big data, patients were extracted through the diagnosis of lipid metabolic disease, and the risk of secondary cancer was compared according to the presence or absence of thyroid cancer. In the analysis of institutional data, the risk of secondary cancer increased by approximately two-fold compared to that in patients without thyroid cancer. Interestingly, the risk of secondary cancer was not significantly increased in the patient group with both non-alcoholic fatty liver disease and dyslipidemia. Thyroid cancer increases the risk of secondary cancer in patients with lipid metabolic diseases such as non-alcoholic fatty liver disease and dyslipidemia. When the two diseases coexist, there is no further increase in the risk of secondary cancers. In the nationwide cohort, univariate and multivariate analyses indicated that hazard ratios of thyroid cancer were 1.329 (95% confidence interval [CI], 1.153–1.533) and 1.301 (95% CI, 1.115–1.517), respectively. In the risk analysis of individual cancers, lip, tongue, mouth, lung, bone, joints, soft tissue, skin, brain, and male cancers and lymphoma showed significantly increased hazard ratios after the occurrence of thyroid cancer. As a result of analysis according to thyroid hormone replacement, which can be an external factor affecting the occurrence of secondary cancer in patients with thyroid cancer, analysis of institutional data showed that the risk of secondary cancer decreased with long-term use. In the population-based cohort analysis, 261,598 patients who underwent surgery for thyroid cancer were included. Among them, 11,790 patients had a second primary cancer and 47,160 patients without secondary primary cancer were matched. The average dose of thyroid hormone also increased the adjusted odds ratio (OR) in both low (≤ 50 μg, OR 1.29, CI 1.12–1.48) and high (> 100 μg, OR 1.24, CI 1.12–1.37) doses. Analyzing over time, the adjusted OR of second primary cancer was increased compared to patients without thyroid hormone administration, especially in short (≤ 1 year) duration, 1.29 (CI, 1.12–1.48), and long (> 5 years) duration, 1.24 (CI, 1.12–1.37). Thyroid cancer in patients with dyslipidemia or non-alcoholic fatty liver disease might be a valuable factor for predicting the development of other cancers, and insufficient and excessive thyroid hormone replacement might be linked to increased secondary cancer in patients undergoing thyroidectomy.