| Title: | Genetics, primary care records and lifestyle factors for short-term dynamic risk prediction of colorectal cancer: prospective study of asymptomatic and symptomatic UK Biobank participants |
| Journal: | BMJ Oncology |
| Published: | 18 Feb 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40046831/ |
| DOI: | https://doi.org/10.1136/bmjonc-2024-000336 |
Publication 15266
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Objectives: To quantify the contributions of polygenic scores, primary care records (presenting symptoms, medical history and common blood tests) and lifestyle factors, for short-term risk prediction of colorectal cancer (CRC) in general and symptomatic individuals.</p>
Methods and analysis: This prospective cohort study used data from the UK Biobank with follow-up until 2018. It included 160 507 participants with linked primary care records and a subcohort of 42 782 participants with recent CRC-related symptoms. The outcome was the first-recorded CRC diagnosis within 2 years. Dynamic risk models with time-varying predictors were derived using a super-landmark framework. Model discrimination was assessed through Harrel's C-index, and predictor contributions to model discrimination were evaluated using inclusion-order-agnostic Shapley values.</p>
Results: C-indices (95% CIs) were 0.73 (0.72 to 0.73) and 0.69 (0.68 to 0.70) for the general and symptomatic participants, respectively. Shapley contributions to model discrimination (95% CIs) were core predictors (eg, age, sex) 33% (25% to 42%) (symptomatic: 34% (9% to 75%)), polygenic scores 16% (8% to 26%) (8% (-21% to 35%)), primary care blood tests 32% (19% to 43%) (41% (16% to 73%)), medical history 11% (4% to 17%) (9% (-25% to 37%)), lifestyle factors 6% (0% to 11%) (-5% (-32% to 13.4%)) and symptoms 3% (-2% to 7%) (13% (-19% to 41%)).</p>
Conclusions: Polygenic scores contribute substantially to short-term risk prediction for CRC in both general and symptomatic populations; however, the contribution of information in primary care records (including presenting symptoms, medical history and common blood tests) is greater. Lifestyle factors not routinely collected in primary care contribute minimally.</p>
14 Authors
- Samantha Ip
- Hannah Harrison
- Juliet A Usher-Smith
- Matthew E Barclay
- Jonathan Tyrer
- Joe Dennis
- Xin Yang
- Michael Lush
- Cristina Renzi
- Nora Pashayan
- Spiros Denaxas
- Georgios Lyratzopoulos
- Antonis C Antoniou
- Angela M Wood
1 Application
| Application ID | Title |
|---|---|
| 64351 | Risk-stratified early detection and diagnosis of cancer using linked electronic health records (RREDD-HER) |
Enabling scientific discoveries that improve human health