Epidemiology of Endometrial Carcinoma: Etiologic Importance of Hormonal and Metabolic Influences

Abstract

Endometrial carcinoma is the most common gynecologic cancer in developed nations, and the annual incidence is projected to increase, secondary to the high prevalence of obesity, a strong endometrial carcinoma risk factor. Although endometrial carcinomas are etiologically, biologically, and clinically diverse, hormonal and metabolic mechanisms are particularly strongly implicated in the pathogenesis of endometrioid carcinoma, the numerically predominant subtype. The centrality of hormonal and metabolic disturbances in the pathogenesis of endometrial carcinoma, combined with its slow development from well-characterized precursors in most cases, offers a substantial opportunity to reduce endometrial carcinoma mortality through early detection, lifestyle modification, and chemoprevention. In this chapter, we review the epidemiology of endometrial carcinoma, emphasizing theories that link risk factors for these tumors to hormonal and metabolic mechanisms. Future translational research opportunities related to prevention are discussed.

A prospective clinical cohort study of women at increased risk for endometrial cancer

“…While some risk factors including older age, increasing BMI, and smoking (protective), were associated with EC as expected, the established strong protective risk factor OC use was not significantly associated with reduced risk of EC in our study cohort, but instead showed an increased odds ratio. While the association between OC use and EC is strong and undisputed [11,12], approximately 70% of women in our study, including those with a pathologically unremarkable appearing endometrium, reported past OC use compared with 40e50% of women in other population-based cohort studies [29e31]. Thus, the lack of an association between past OC use and EC in our study is likely secondary to higher OC use in our reference group compared to the general population.…”

Napsin-A Expression, a Reliable Immunohistochemical Marker for Diagnosis of Ovarian and Endometrial Clear Cell Carcinomas

“…Endometrial carcinoma is the most common gynecologic cancer in developed countries (11) and ovarian cancer is the fifth frequent tumor in women (12). Clear cell carcinoma is an uncommon subtype of malignant epithelial tumors in ovary and endometrium.…”

The gynecological surveillance of women with Lynch syndrome in Sweden

“…Interestingly, these genes and the transcription factor binding regions in which the five described haplotypes are found have been associated with estrogen-dependent cancers, especially breast cancer. Endometrioid EC is also estrogen-dependent, and the environmental factors associated with this disease are strongly linked to estrogen excess (158)(159)(160), which could explain the increased susceptibility for EC among these haplotypes. Neither potential estrogen excess nor other environmental risk factors for EC have been investigated among the patients and controls in this particular study, which is a weakness of the study design.…”