Ovarian cancer, as the fifth most common cause of cancer death among US women, will take the lives of an estimated 15,500 women in 2012. Ovarian cancer has no symptoms at the early stages, so the disease is generally advanced when it is diagnosed. A majority (63%) of patients are diagnosed with ovarian cancer at advanced stage and have a 27% 5-year survival rate. It has been recognized that early detection of ovarian cancer has the potential to improve prognosis. Matrix metalloproteinases (MMPs) play a critical role in the extracellular matrix remodeling associated with follicular development and are prominently expressed in the early stages of ovarian tumor development. Higher serum MMP levels are associated with progressing stages of ovarian cancer, worse prognosis and higher recurrence. All prior human studies have been conducted using cross-sectional data and thus, unable to establish a temporal relationship between MMP biomarkers and disease. In this proposed project, we will evaluate for the first time, whether MMP levels in urine samples obtained prior to diagnosis are related to the development of ovarian cancer. We will use a nested case- control study of 74 incident ovarian cancer cases and 222 individually matched controls within the Singapore Chinese Health Study, a population-based prospective cohort. With available pre-diagnostic urine samples, the proposed study will provide novel findings that will shed light on the role MMPs have in the development of ovarian cancer. These urinary MMP biomarkers, if their risk assessment role is confirmed, can be developed to monitor the progression of ovarian benign to malignant lesions, leading to the early detection of ovarian cancer when treatments are more effective, and ultimately resulting in fewer women dying from ovarian cancer.
The proposed project will determine whether levels of metalloproteinases in urine can predict the development of ovarian cancer. The results from this project have the potential to substantially reduce ovarian cancer mortality with a non-invasive, urine-based marker of early disease.