Past Awardees

Project: The role of polygenic risk scores in ovarian cancer survival

In the U.S., ovarian cancer is the 5th leading cause of cancer death and the most fatal of the gynecologic cancers. While women with mutations in BRCA1 or BRCA2 (BRCA1/2) are at an increased risk of developing ovarian cancer, studies have shown a short-term survival advantage for women with BRCA1/2-mutated ovarian cancer. In addition to these highly penetrant genes, polygenic risk scores (PRS), which aggregate risks from common low-risk single nucleotide polymorphisms (SNPs), have been associated with ovarian cancer risk; however, no study has examined the role of PRS in ovarian cancer survival. Given the poor prognosis of ovarian cancer, and the potential survival differences between high and average risk women, it is critical to identify novel biomarkers of prognosis that can improve clinical and treatment decisions. Therefore, we are proposing to generate PRS for women with ovarian cancer in the UK Biobank (n=1,432), a large international dataset with extensive cancer outcomes and genomic data, and to assess differences in tumor characteristics and overall survival (OS) by BRCA1/2 pathogenic variant status and PRS. The results from this award will provide critical data for the submission of a larger grant focused on developing prognostic models for ovarian cancer which incorporate genetic factors (e.g., pathogenic variants in relevant genes, PRS) and important patient, tumor, and treatment characteristics, to reduce the burden of this highly fatal disease.