Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026
Using Polygenic Risk Scores to Refine Risk and Outcomes in High-grade Serous Ovarian Cancer in Australia.
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Delahunty Rachel, Silva S Sandun M, Pandey Ahwan, Garsed Dale W, Beesley Jonathan, Fereday Sian, Traficante Nadia, Craig Stuart, Nguyen Linh N, Hendley Joy, Christie Elizabeth L, Webb Penelope M, Chenevix-Trench Georgia, Bowtell David D L, Alsop Kathryn, Jayawardana Madawa, James Paul A
Аннотация
BACKGROUND: Ovarian cancer is characterized by high mortality and lacks effective screening, making prevention critical. A polygenic risk score (PRS), which aggregates the effects of multiple common alleles, may capture a proportion of currently unexplained genetic risk. Although PRSs have been evaluated for risk prediction, their association with treatment response and survival remains unclear. This study assessed the utility of a PRS for predicting high-grade serous ovarian cancer (HGSOC) risk in an Australian population and its association with chemotherapy response and outcomes.
METHODS: PRSs were calculated for 1,097 cases with HGSOC and 812 controls using data from Australian research programs. Associations among PRS, ovarian cancer risk, chemotherapy response, and survival were analyzed.
RESULTS: Each standard-deviation increase in PRS was associated with a 40% increase in HGSOC risk [odds ratio (OR), 1.40; P < 0.001]. Women in the top 1% of the PRS distribution had a lifetime ovarian cancer risk approaching 3%. Higher PRS values showed a trend toward poorer outcomes; however, these associations were not consistent across analyses.
CONCLUSIONS: PRSs were not clearly associated with chemotherapy response or survival but represent a significant risk factor for the development of HGSOC. Incorporating PRS into clinical models may improve risk stratification and support targeted prevention.
IMPACT: As the first study to evaluate how PRS relates to both HGSOC risk and chemotherapy response and outcomes, we show that PRSs are unlikely to serve as therapeutic biomarkers but support their use for enhanced risk-stratified prevention.
METHODS: PRSs were calculated for 1,097 cases with HGSOC and 812 controls using data from Australian research programs. Associations among PRS, ovarian cancer risk, chemotherapy response, and survival were analyzed.
RESULTS: Each standard-deviation increase in PRS was associated with a 40% increase in HGSOC risk [odds ratio (OR), 1.40; P < 0.001]. Women in the top 1% of the PRS distribution had a lifetime ovarian cancer risk approaching 3%. Higher PRS values showed a trend toward poorer outcomes; however, these associations were not consistent across analyses.
CONCLUSIONS: PRSs were not clearly associated with chemotherapy response or survival but represent a significant risk factor for the development of HGSOC. Incorporating PRS into clinical models may improve risk stratification and support targeted prevention.
IMPACT: As the first study to evaluate how PRS relates to both HGSOC risk and chemotherapy response and outcomes, we show that PRSs are unlikely to serve as therapeutic biomarkers but support their use for enhanced risk-stratified prevention.