Mary Playdon

Ph.D., M.P.H.

Huntsman Cancer Institute

Assistant Professor

PLCO (Learn more about this study)

2017-0020

Jun 29, 2017

Blood metabolite profiles and risk of developing endometrial cancer

Endometrial cancer is the most common gynecological cancer, and incidence and mortality rates are increasing worldwide. Endometrial cancers are associated with common metabolic perturbations, several of which are obesity-driven but some that are also independent of obesity. Many are thought to be modifiable by diet; however, diet associations with endometrial cancer have been difficult to observe, in part due to limitations of traditional self-reported dietary questionnaires, which can attenuate diet-cancer relationships. Furthermore, not all women that are obese exhibit metabolic dysfunction, while a subset of non-obese women have abnormal metabolic profiles. Therefore, metabolic dysfunction may be a risk factor for endometrial cancer, independent of body mass index (BMI). Important additional research is needed, including leveraging novel methods like metabolomics, which measures products of metabolism, for exploring the mechanisms that drive endometrial cancer, and how they relate to obesity and diet. These novel methods can also be used to improve dietary measurement using objective biomarkers. The proposed studies utilize a novel metabolomics method to improve our understanding of the biological pathways and mechanisms involved in endometrial cancer development, including those that are independent of known risk factors and those related to known risk factors (e.g. diet or being overweight or obese). We propose to evaluate metabolite associations with endometrial cancer using data from nested case-controls studies within four prospective cohorts, and to meta-analyse results for enhanced statistical power. This project will advance the field by (1) uncovering unknown/underappreciated metabolic pathways involved in the etiology of endometrial cancer that are independent of known endometrial cancer risk factors to inform novel risk factors; and (2) determine metabolic mediators of associations between known endometrial risk factors (diet and adiposity) and endometrial cancer to inform molecular pathways for creation and evaluation of cancer prevention interventions and for use in future risk prediction models.