The oversimplification of uterine cancer classifications and risk factors

We appreciate Dr Sarkar and colleagues for their interest and thoughtful comments on our study titled “The association of obesity and type I uterine cancer-is this an oversimplification?.” We agree with their comment that a direct analysis evaluating obesity in those presenting with nonendometrioid tumors is important. However, this would require a prospective, longitudinal cohort study over many years to accomplish. Our analysis focused on the use of population-level data over 2 decades to evaluate the association between obesity and the rising rate of high-risk, nonendometrioid tumors. Of note, one of the significant weaknesses of our study involved the use of 2 national databases that limited our ability to perform a direct correlation because of the lack of patient-level data. When patient-level data were available in smaller epidemiologic studies, evidence suggested overlapping risk factors between types I and II endometrial cancers, including obesity.¹ Thus, our findings have added to the growing body of literature that suggests that obesity may play a role in high-risk, nonendometrioid tumors.

Given the rising incidence and mortality of endometrial cancer, we hope these findings will direct future research to explore the effect of obesity on the incidence of nonendometrioid tumors. Ideally, as Dr Sakar and colleagues noted, such a study would include an analysis of body mass index and its association with the types of endometrial cancer according to the molecular classification suggested by the Cancer Genome Atlas.² Furthermore, it would ideally include a longitudinal, international analysis evaluating the effect of all other known and potentially unknown risk factors, such as demographic, socioeconomic, environmental, dietary, physical activity, family, hormonal, menstrual, parity, genetic, proteomic, metabolomic, epigenetic, and microbiomic factors. The role of obesity on type II tumors and the entirety of the traditional type I or II classification system may be oversimplified in light of the molecular classification of endometrial cancer.³ Future studies should aim to validate a molecular classification system and determine associated modifiable risk factors to decrease the rising incidence and mortality associated with endometrial cancer.