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Abstract Poorly differentiated thyroid carcinoma (PDTC) is a subtype of thyroid cancer that has a high rate of metastasis or recurrence and a relatively poor prognosis. However, there are few studies that have been conducted on PDTC at the whole protein-coding gene scale. Here, we performed genomic profiling of 15 patients with PDTC originated from follicular thyroid carcinoma using whole exome sequencing and also performed gene functional enrichment analysis of differentially expressed genes (DEGs) for three patients. Further, we investigated genetic variants associated with PDTC progression and the characteristics of clinical pathology. We revealed somatic genomic alterations in the RAF1, MAP2K2, and AKT2 genes that were not reported in previous studies. We confirmed frequent occurrences in the RAS gene in patients with PDTC; the genetic alterations were associated with the RAS-RAF-MEK-ERK/JNK, PI3K-AKT-mTOR signaling pathways, and the cell cycle. DEG analysis showed that immune response was lower in cancer tissues than in normal tissues. Through the association analysis of somatic mutations and the characteristics of clinical pathology from patients with PDTC, the somatic mutations of ABCA12, CLIP1, and ATP13A3 were significantly associated with a vascular invasion phenotype. By providing molecular genetic insight on PDTC, this study may contribute to the discovery of novel therapeutic target candidates.

Abstract In order to analyze the associations between thyroid cancer and environmental factors, we analyzed the national sample cohort representative of the entire population provided by the Korean National Health Insurance Service database record from 2006 to 2015. The cohort was categorized according to age, body mass index, income, residential areas, frequency of exercise, frequency of alcohol drinking, diet, presence or absence of hyperthyroidism, presence or absence of hypothyroidism, and smoking data. Age ≥ 55 years (HR 0.68, 95% CI 0.53–0.88), lower income (0.57, 0.40–0.80), and current smoking (0.69, 0.55–0.85) were associated with lower thyroid cancer occurrence among men. Body mass index (BMI) ≥ 25 kg/m2 (1.51, 1.26–1.82), higher income (1.44, 1.19–1.76), urban residence (1.24, 1.03–1.49), and presence of hypothyroidism (3.31, 2.38–4.61) or hyperthyroidism (2.46, 1.75–3.46) were associated with higher thyroid cancer occurrence among men. Age ≥ 55 years (0.63, 0.56–0.71), moderate alcohol drinking (0.87, 0.77–0.99), and current smoking (0.56, 0.37–0.85) were associated with lower thyroid cancer occurrence among women. BMI ≥ 25 kg/m2 (1.41, 1.26–1.57), frequent exercise (1.21, 1.07–1.36), higher income (1.18, 1.06–1.32), urban residence (1.17, 1.06–1.29), and presence of hypothyroidism (1.60, 1.40–1.82) or hyperthyroidism (1.38, 1.19–1.61) were associated with higher thyroid cancer occurrence among women. In conclusion, age ≥ 55 years and current smoking were associated with lower thyroid cancer occurrence, while BMI ≥ 25 kg/m2, higher income, urban residence, hypothyroidism, and hyperthyroidism were associated with higher occurrence in both men and women.