Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease.
Publication Title
NPJ Genom Med
Document Type
Article
Publication Date
3-5-2024
Keywords
oregon; medford; genomics
Abstract
Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10-8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56? subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.
Area of Special Interest
Women & Children
Area of Special Interest
Cancer
Specialty/Research Institute
Obstetrics & Gynecology
Specialty/Research Institute
Oncology
Specialty/Research Institute
Epidemiology
DOI
10.1038/s41525-024-00395-y
