Grant: Project Grant - PA: Women's Health Research - Early Career Researcher Grant

Up until recently, researchers have believed that genetic mutations that control critical cell functions were exclusively linked to the onset and progression of cancer. Our group, and others, have recently shown that normal tissue can survive with cancer-associated mutations, without becoming cancer or exhibiting any changes under the microscope. Cells in the uterus seem to naturally acquire these mutations over time. Mutations can appear early in life, with ~30% of individuals having a detectable mutation in their uterus at age of 20 and up to ~80% by menopause, without any microscopic signs of abnormality. We aim to better understand what this may mean for an individual's reproductive and general health. The study of so-called cancer mutations in normal and non-cancer conditions is extremely new, enabled by advances in DNA sequencing technologies that emerged in the last decade. The effects of mutations on individual cells and uterine conditions remain unclear; these may contribute to risk of not only cancer, but also far more common non-cancer conditions, such as endometriosis, adenomyosis, endometrial polyps, abnormal uterine bleeding, infertility, and other uterine conditions. Though not life-threatening, the latter conditions greatly affect quality of life, fertility, and incidence of chronic health conditions, and risk of future cancers. This project will seek to evaluate whether individuals with cancer-gene mutations in normal-looking uterine cells are more likely to experience either cancer or non-cancer conditions later in life. We will also use a mouse model system to study how the presence of these mutations may affect how the uterus functions and responds to hormonal cycling.