Background: The American Cancer Society (ACS) estimated 56,870 new cases of thyroid cancer in the United States in 2017, with roughly 2,010 deaths attributed to the disease. The incidence of thyroid cancer has been increasing steadily over the past three decades, with Papillary Thyroid Cancer (PTC) being the most prevalent form of this endocrine malignancy, comprising of about 90% of all cases. Appreciably, Surveillance, Epidemiology, and End Results (SEER) and the ACS indicate that the incidence of PTC in the age group of 20-49 years is three to four times more prevalent in women than in men. This epidemiologic finding suggests that the female thyroid is at a higher risk of developing PTC.

Methods: The Cancer Genome Atlas (TCGA) database provides the means to address the differences between male and female thyroids on the molecular level. Using the normalized Level 3 RNA Seq Data and patient pathology reports available on the TCGA Data Portal, differential gene expression of 56 non-neoplastic/normal thyroid samples (40 women; 16 men) was investigated using the biological analysis software, Subio platform, version v1.20.5031. (Subio Inc., Tokyo, Japan).

Results: Immune/inflammatory genes exhibited a higher expression in uninflamed, normal thyroid tissue of women than in men (>1.5 fold; p<0.05). The expression levels of these genes were increased in male PTC samples, compared to their matched normal tissue. The level of expression of immune/inflammatory genes in women approximated their expression levels in matched PTC tissue of women and men, indicating that normal thyroid tissue in women exhibits a neoplastic level of inflammation.

Conclusions: Our data suggest that the female thyroid may be “at-risk” for developing PTC due to underlying and on-going immune/inflammatory processes.

Citation Format: Anvita Gupta, Karnika Singh, Timmy J. O'Connell, Melanie Jones, JK Rasamny, Monica Schwarcz, Augustine Moscatello, Edward Shin, Raj Tiwari, Jan Geliebter. Underlying inflammatory processes in non-neoplastic female thyroid serve as an immunological basis for the sex disparity in papillary thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5750.