Association between polygenic risk and survival in breast cancer patients

Polygenic risk scores (PRS) estimate an individual’s germline genetic predisposition to a quantitative trait and/or risk of disease. Several PRS have been developed for cancer risk with the goal of improved risk screening. Here, we sought to establish whether PRS for cancer risk and other common traits may influence survival for patients with cancer. We conducted a PRS survival analysis using 23,770 cancer patients of European ancestry from the Dana-Farber Cancer Institute Profile cohort. We identified an association between PRS for breast cancer risk and longer patient survival (HR = 0.89 (95% CI: 0.84–0.95), p = 1.50 × 10–4, < 5% FDR), implying that individuals at high genetic risk had better outcomes. High PRS individuals were also significantly less likely to harbor somatic TP53 mutations, consistent with having less aggressive tumors. This association persisted when including tumor grade and became more protective when restricting to ER-negative tumors (HR = 0.78 (95% CI: 0.68–0.89), p = 1.69 × 10–4). Potential confounders such as hormone receptor status, age, grade, stage, and ER-targeted therapy did not fully explain this association, nor was there statistical evidence of index event bias at individual variants. We did not observe significant associations between cancer risk and survival for other cancers, suggesting that this mechanism may be largely unique to breast cancer. However, we did observe associations between shorter survival and type 2 diabetes, bipolar, and pancreatitis PRS (1% FDR). These findings suggest that higher germline risk may predispose individuals to less aggressive breast cancer tumors and provide novel insights into breast cancer development and prognosis.

Authors

Institutions

Publication Details

Journal
BMC Cancer
Published
2025-08-28
DOI
https://doi.org/10.1186/s12885-025-14640-9
Citations
1
Primary Topic
Genetic Associations and Epidemiology
Type
article
Field-Weighted Citation Impact
1.82

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Association between polygenic risk and survival in breast cancer patients

Yi Ding, Will Freyman, Ethan M. Jewett, Anjali J. Shastri et al.
1 citations
BMC Cancer
Genetic Associations and Epidemiology
1.82
article

Association between polygenic risk and survival in breast cancer patients

Yi Ding, Will Freyman, Ethan M. Jewett, Anjali J. Shastri, G. David Poznik, Stefan Groha, Keaton Stagaman, Shubham Saini, Teague Sterling, Meghan E. Moreno, Morgan Schumacher, Jared O’Connell, Stella Aslibekyan, Jingchunzi Shi, Steven J. Micheletti, Michał Kmiecik, Yunxuan Jiang, Dominique T. Nguyen, Julie M. Granka, Barry Hicks, Michael V. Holmes, Chris Eijsbouts, Vinh Tran, Chris German, Alan Kwong, M. Reza Jabalameli, Katelyn Kukar, Pierre Fontanillas, Ninad S. Chaudhary, Alexander Gusev, Payam Dibaeinia, Davide Foletti, Danielle E. Kurant, Éadaoin Harney, Alejandro Hernandez, Amy Lavin Williams, Alexandra Reynoso, Keng‐Han Lin, Catherine H. Weldon, Peter Wilton, Teresa Filshtein, Steve Pitts, Yanyu Liang, Jessica Bielenberg, Elizabeth Babalola, Qiaojuan Jane Su, Suyash Shringarpure, Leah Selcer, Emily DelloRusso, Sotiris Karagounis, Xin Wang, Wei Wang, Sayantan Das, Nicholas Eriksson, Priyanka Nandakumar, Aly Khan, Joyce Y. Tung, Zach Fuller, Adam Auton, Robert K. Bell, Lucy Kaufmann, David A. Hinds, Sarah L. Elson, Bianca A. Llamas, Susana A. Tat, Matthew H. McIntyre, Zayn Cochinwala
article en
1 citations

Abstract

Polygenic risk scores (PRS) estimate an individual’s germline genetic predisposition to a quantitative trait and/or risk of disease. Several PRS have been developed for cancer risk with the goal of improved risk screening. Here, we sought to establish whether PRS for cancer risk and other common traits may influence survival for patients with cancer. We conducted a PRS survival analysis using 23,770 cancer patients of European ancestry from the Dana-Farber Cancer Institute Profile cohort. We identified an association between PRS for breast cancer risk and longer patient survival (HR = 0.89 (95% CI: 0.84–0.95), p = 1.50 × 10–4, < 5% FDR), implying that individuals at high genetic risk had better outcomes. High PRS individuals were also significantly less likely to harbor somatic TP53 mutations, consistent with having less aggressive tumors. This association persisted when including tumor grade and became more protective when restricting to ER-negative tumors (HR = 0.78 (95% CI: 0.68–0.89), p = 1.69 × 10–4). Potential confounders such as hormone receptor status, age, grade, stage, and ER-targeted therapy did not fully explain this association, nor was there statistical evidence of index event bias at individual variants. We did not observe significant associations between cancer risk and survival for other cancers, suggesting that this mechanism may be largely unique to breast cancer. However, we did observe associations between shorter survival and type 2 diabetes, bipolar, and pancreatitis PRS (1% FDR). These findings suggest that higher germline risk may predispose individuals to less aggressive breast cancer tumors and provide novel insights into breast cancer development and prognosis.

BMC CancerVol. 25(1)
Harvard University (US), 23andMe (United States) (US), Dana-Farber Cancer Institute (US)
National Institutes of Health, National Human Genome Research Institute
Good health and well-being
Openalex Percentile: Top 13%
Genetic Associations and Epidemiology
1.82
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.