Bhatt, Rikesh;
(2024)
Estimation of age of onset and progression of breast cancer by absolute risk dependent on polygenic risk score and other risk factors.
Cancer
10.1002/cncr.35183.
(In press).
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Abstract
Background: Genetic, lifestyle, reproductive, and anthropometric factors are associated with the risk of developing breast cancer. However, it is not yet known whether polygenic risk score (PRS) and absolute risk based on a combination of risk factors are associated with the risk of progression of breast cancer. This study aims to estimate the distribution of sojourn time (pre-clinical screen-detectable period) and mammographic sensitivity by absolute breast cancer risk derived from polygenic profile and the other risk factors. Methods: The authors used data from a population-based case-control study. Six categories of 10-year absolute risk based on different combinations of risk factors were derived using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm. Women were classified into low, medium, and high-risk groups. The authors constructed a continuous-time multistate model. To calculate the sojourn time, they simulated the trajectories of subjects through the disease states. Results: There was little difference in sojourn time with a large overlap in the 95% confidence interval (CI) between the risk groups across the six risk categories and PRS studied. However, the age of entry into the screen-detectable state varied by risk category, with the mean age of entry of 53.4 years (95% CI, 52.2–54.1) and 57.0 years (95% CI, 55.1–57.7) in the high-risk and low-risk women, respectively. Conclusion: In risk-stratified breast screening, the age at the start of screening, but not necessarily the frequency of screening, should be tailored to a woman’s risk level. The optimal risk-stratified screening strategy that would improve the benefit-to-harm balance and the cost-effectiveness of the screening programs needs to be studied.
| Type: | Article |
|---|---|
| Title: | Estimation of age of onset and progression of breast cancer by absolute risk dependent on polygenic risk score and other risk factors |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/cncr.35183 |
| Publisher version: | https://doi.org/10.1002/cncr.35183 |
| Language: | English |
| Additional information: | © 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| Keywords: | absolute risk, breast cancer, multistate model, natural history, polygenic risk score, sensitivity,sojourn time |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10184935 |
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