Short Non-coding RNA Biomarkers of Predisposition to Ovarian Cancer

A Pilot Study of Short Non-coding RNA Biomarkers of Predisposition to Ovarian Cancer

The purpose of this study is to create new tests to identify biomarkers for ovarian cancer so that a screening test can be developed. For patients who have a diagnosis of ovarian Cancer, researchers will use blood samples before and after treatment to see if disease status can be determined by measuring the amount of biomarker.

Epithelial ovarian cancer is the most lethal female reproductive malignancy, mainly because 80% of tumors have metastasized beyond the ovary at the time of diagnosis. Screening efforts aimed at improved identification of early stage disease have been largely unsuccessful, because of ovarian cancer's propensity for early spread. Our hypothesis is that this obstacle can be circumvented by identifying biomarkers for the precancerous stage of this disease. Since this pre-cancerous stage is currently undetectable, we instead propose to look for biomarkers in women at very high risk for developing ovarian cancer due to genetic mutations. We hypothesize that identification of markers for genetic predisposition to ovarian cancer will also be informative for detection of biological changes that over time lead to sporadic cancers. Given their increasingly recognized role in states of normal and abnormal growth and differentiation, we hypothesize that short non-coding RNAs (sncRNAs) hold significant promise as biomarkers of ovarian cancer predisposition. We will test these hypotheses in two aims. First, we will identify biomarkers for hereditary ovarian cancer risk by comparing serum-derived sncRNAs in women with and without hereditary risk for ovarian cancer. In the second aim we will define serum-derived sncRNAs correlates of ovarian cancer disease status. We will compare sera from ovarian cancer patients at times of highest and lowest disease burden to those of control, cancer-free subjects. Each aim will provide independent, novel, and important information for future investigations. The sncRNAs found to be differentially expressed in both aims will be prioritized for future validation in women under clinical surveillance for hereditary risk of ovarian cancer.

Inclusion Criteria:

• Undergoing medical care at UVA

• Up to date breast cancer screening

• Subjects must fall into one of the following groups:

  • Women at increased risk of ovarian cancer based on family history, personal history, or genetic factors defined as either BRCA1 or BRCA2 mutations who still retain both fallopian tubes and both ovaries.
  • Women at average risk for ovarian cancer
  • Women with known/suspected or recurrent ovarian cancer who are undergoing evaluation and/or treatment at UVA Cancer Center

Exclusion Criteria:

• Subjects with increased risk for ovarian cancer may not have a history of prior malignancy within the last 10 years excluding cervical carcinoma in situ or basal cell carcinoma
• Pregnancy (self reported)