# Genome-wide association study of 398,238 women unveils seven loci associated with high-grade serous ovarian cancer

## TL;DR

This study identified new genetic variants linked to high-grade serous ovarian cancer in over 398,000 women, improving risk prediction.

## Contribution

The study reports eight novel HGSOC susceptibility loci and a strong polygenic score for risk prediction.

## Key findings

- Eight novel variants were associated with high-grade serous ovarian cancer risk.
- A TP53 3’-UTR SNP (rs78378222-T) showed a significant association with HGSOC (RR = 1.44).
- A polygenic score using 64,518 variants improved HGSOC risk prediction in UK Biobank (OR = 1.46).

## Abstract

Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We meta-analyzed >22 million variants for 398,238 women from the Ovarian Cancer Association Consortium (OCAC), UK Biobank (UKBB) and Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA) to identify novel HGSOC susceptibility loci. Eight novel variants were associated with HGSOC risk. An interesting discovery biologically was TP53 3’-UTR SNP rs78378222-T’s association with HGSOC (per-T-allele relative risk (RR) = 1.44, 95% CI:1.28–1.62, P = 1.76 × 10−9). Polygenic scores (PGS) were developed using OCAC and CIMBA data and trained on FinnGen data. The optimal PGS included 64,518 variants and was associated with an odds ratio of 1.46 (95% CI:1.37–1.54) per standard deviation when validated in the UKBB. This study represents the largest HGSOC GWAS to date – demonstrating that improvements in imputation reference panels and increased sample sizes help to identify HGSOC associated variants that previously went undetected, ultimately improving PGS which can improve personalized HGSOC risk prediction.