Thyroid cancer gender disparity

Abstract

Cancer gender disparity in incidence, disease aggressiveness and prognosis has been observed in a variety of cancers. Thyroid cancer is one of the fastest growing cancer diagnoses worldwide. It is 2.9-times more common in women than men. The less aggressive histologic subtypes of thyroid cancer are more common in women, whereas the more aggressive histologic subtypes have similar gender distribution. The gender disparity in incidence, aggressiveness and prognosis is well established for thyroid cancer but the cause of the disparity is poorly understood. The aim of this article is to evaluate the current evidence on the cause of thyroid cancer gender disparity. Dietary and environmental factors do not appear to have a significant role in thyroid cancer gender disparity. Common somatic mutations in BRAF, rearranged in transformation/papillary thyroid carcinomas (RET/PTC) and neurotrophin receptor-tyrosine kinase (NTRK) also do not account for the gender disparity in thyroid cancer. While reproductive factors would seem a logical hypothesis to account for the gender disparity, there appears to be no conclusive effect on the risk of developing thyroid cancer. Recent studies on estrogen receptor status in thyroid cancer show a difference in the receptor subtypes expressed based on the histology of thyroid cancer. Moreover, the response to estrogen is dependent on the specific estrogen receptor expressed in thyroid cancer cells. However, what determines the tumor-specific sex hormone receptor expression is unclear. No established molecular factors appear to explain gender differences in thyroid cancer. Therefore, the application of high-throughput genomic and proteomic approaches to the study of thyroid cancer gender disparity could be helpful for better understanding the molecular basis for gender differences in thyroid and other cancers.

Figure 1. Thyroid cancer incidence and mortality

(A) Thyroid cancer incidence by age and gender. (B) Thyroid cancer mortality rates by age and gender. Rates per 100,000 persons from 2003 to 2007. Data from the Survellance, Epidemiology and End Results (SEER) Program using 12 SEER areas (San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, Atlanta, San Jose–Monterey, Los Angeles and Alaska) [101].

Figure 2. Thyroid carcinogenesis model

Genetic changes that are involved in thyroid carcinogenesis, such as BRAF, RET/PTC and RAS mutations that occur in benign and malignant thyroid neoplasm of follicular cell origin, as well as epigenetic changes that result in gene silencing of thyroid follicular cell growth-regulatory hormones are risk factors for thyroid cancer. Two established risk factors that are associated with higher risk of thyroid cancer and benign neoplasm are radiation exposure and family history of thyroid cancer. However, none of these factors are associated with gender difference in thyroid cancer of follicular cell origin.