| Title: | Predicting 10-Year Risk of Pancreatic Cancer Using a Combined Genetic and Clinical Model |
| Journal: | Gastro Hep Advances |
| Published: | 12 Jun 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39130772/ |
| DOI: | https://doi.org/10.1016/j.gastha.2023.05.008 |
Publication 10513
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Abstract
Background and Aims: Pancreatic cancer has the poorest 5-year survival rate of any major solid tumor, but when diagnosed at an early stage, survival rates improve. Population screening is impractical because pancreatic cancer is rare with a lifetime risk of 1.7%, but accurate risk stratification in the general population could enable health care providers to focus early detection strategies to at-risk individuals. Here, we validate a combined risk prediction model that integrates a polygenic risk score and a clinical risk model.</p>
Methods: Using the UK Biobank, we conducted a prospective cohort study assessing 10-year pancreatic cancer risks based on a polygenic risk score, a clinical risk score, and a combined risk score. We assessed the association, discrimination, calibration, cumulative hazards, and standardized incidence ratios compared to population incidence rates for the risk scores. We also conducted net reclassification analyses.</p>
Results: While all of the risk scores discriminated well between affected and unaffected participants, the combined risk score - with a Harrell's C-index of 0.714 (95% confidence interval [CI] = 0.698, 0.730) - discriminated better than both the polygenic risk score (P = .001) and the clinical risk score (P = .02). In terms of calibration, there was no problem with dispersion for the combined risk score (β = 0.952, 95% CI = 0.865-1.039, P = .3) and overall there was a small overestimation of risk (α = -0.089, 95% CI = -0.156 to -0.021, P = .009). Participants in the top decile of 10-year risk were at 1.413 (95% CI = 1.242-1.607) times population risk.</p>
Conclusion: The combined risk score was able to identify individuals at substantially increased risk of pancreatic cancer and to whom targeted screening could be useful.</p>
5 Authors
- Gillian S. Dite
- Erika Spaeth
- Chi Kuen Wong
- Nicholas M. Murphy
- Richard Allman
1 Application
| Application ID | Title |
|---|---|
| 47401 | Validation of polygenic risk scores, based upon pooled discovery studies, for predisposition to major prevalent diseases affecting both quality-of-life and lifespan and testing for causation. |
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