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. Keywords disparity; gender; genetics; molecular basis; papillary thyroid cancer; risk factors; thyroid cancer Cancer gender disparity in incidence, disease aggressiveness and prognosis has been observed for a variety of cancers. In sex-specific organs, such as the uterus, prostate, ovary and breast, this disparity can easily be explained. However, some sex-shared sites, such as the thyroid, lung and liver, also show clear gender differences in incidence and/or survival [1][2][3][4]. Although the incidence of lung cancer in men is on the decline, rates are increasing in women with a projected equalization in rate over the next decade [1,4]. In lung cancer, women are more likely to have adenocarcinoma, present at an earlier stage of disease, and Financial & competing interests disclosureThe authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance w...

Secular trends in the prognostic factors for papillary thyroid cancer

“…A recent epidemiologic study has also demonstrated a better prognosis in younger female patients (!55 years), before menopause, and those aged O55 years had similar outcomes to those of male patients, suggesting a sex disparity in thyroid cancer outcomes (10). However, the beneficial effect of hormones in female patients remains unclear (14), and our results are not consistent with the results mentioned above; in our study, improved prognosis in female patients was observed in those !65 years, and in the patients in the post-1999 time period, the differences in the prognostic outcomes between the sexes were no longer observed for any age group (data not shown).…”

“…Several studies have reported that male sex is a significant prognostic factor for mortality, suggesting a protective effect of being female owing to hormonal effects (14). Experimental studies have revealed inhibitory effects of the estrogen receptor beta on the development of thyroid cancer (15,16).…”

Sexual dimorphism in cancer

“…Even though several studies tried to find associations between this neoplasm and hormonal or dietary factors, the reasons for this discrepancy are still unclear 3 . However, experimentally, it should be noted that AR expression in thyroid follicular cells was reported to reduce proliferation 100 , while estrogen treatment induced proliferation and suppressed apoptosis 101 , suggesting a possibly opposite role of sex hormones in this context.…”

“…Overall, females have a lesser risk and better prognosis than males in a wide range of cancer types unrelated to reproductive function, such as those of colon, skin, head/neck, esophagus, lung and liver 1,2 ( Figure 1). Only very few exceptions exist in which incidence is higher in women, specifically thyroid cancer 3 . Noteworthy, this trend is observed independently to the ethnicity of the studied population.…”

Epidemiology of head and neck cancer in Thailand

“…4 Thyroid carcinoma has a prominent gender disparity with a femaleto-male ratio exceeding 3:1. 38 In 2011, the mean annual incidence of thyroid malignancies in Thailand was 1.5 and 5.1 per 100 000 of male and female population, respectively (Table 1). 4 and 2012.…”