In the U.S., cancer of the endometrium is the most common cancer of the female reproductive organs. Diagnoses of endometrial cancer (EC) have increased worldwide in recent years. The American Cancer Society’s 2018 estimates for cancer of the uterus in the U.S. are:
Our research at the Channing Division of Network Medicine seeks to elucidate mechanisms of cancer causation using a molecular epidemiology approach. This approach combines epidemiology and molecular biology techniques to identify and subsequently characterize biological markers that can then be used in the study of carcinogenic mechanisms. This approach has been applied to understanding the etiology of EC and breast cancers.
Findings from our early sequencing studies revealed that our newly discovered variants in the progesterone receptor increase the risk of both cancers with similar molecular mechanisms (De Vivo et al 2002). We also have experience in conducting whole-genome association studies (De Vivo et al 2014) and exome-wide association studies (Chen et al 2014). And we have measured biomarkers in tumor tissue specimens to better understand variation in endometrial tumor biology. Both risk factors and tissue biomarkers account for different molecular profiles of tumors and which molecular characteristics are associated with aggressive tumor behavior (Busch 2017 and Busch 2018).
Tissue measurements have played an especially important role in our evaluation of candidate markers to define molecular subtypes of EC. Further tissue work is underway comparing molecular and histologic classifications of endometrial tumors. Understanding these cellular consequences of cancer therapy has direct clinical relevance for potentially identifying shortened telomeres (senescent cells) as a marker for long-term treatment-induced side effects and outcomes, or as a target for drug therapy to reduce these adverse sequelae in patients who have been treated for cancer.
We have identified nine new susceptibility loci for endometrial cancer.
Meta-dimensional data integration
We lead the NCI-sponsored international endometrial cancer consortium (E2C2) of 40 national and international studies to conduct the genome-wide association studies (GWAS)/exome-wide association studies (EWAS) of EC that identified additional genetic loci. Our collaborators include:
