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  1. Home
  3. Predicting Pancreatic Cancer In The Uk Biobank Cohort Using Polygenic Risk Scores And Diabetes Mellitus.
  1. Home
  3. Predicting Pancreatic Cancer In The Uk Biobank Cohort Using Polygenic Risk Scores And Diabetes Mellitus.

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Predicting Pancreatic Cancer in the UK Biobank Cohort Using Polygenic Risk Scores and Diabetes Mellitus.

Shreya Sharma1, William J Tapper1, Andrew Collins2

  • 1University of Southampton, Human Development and Health, Southampton, United Kingdom.

Gastroenterology
|January 23, 2022

View abstract on PubMed

Summary
This summary is machine-generated.

Polygenic risk scores (PRS) can identify individuals at higher risk for pancreatic cancer, especially those with new-onset diabetes mellitus (NODM). This PRS may aid in secondary screening for PDAC in high-risk NODM patients.

Keywords:
Early DetectionGenetic Risk ScorePancreatic Adenocarcinoma

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Area of Science:

  • Oncology
  • Genetics
  • Endocrinology

Background:

  • Diabetes mellitus (DM) is linked to pancreatic ductal adenocarcinoma (PDAC).
  • New-onset DM (NODM) is a significant indicator for PDAC.
  • Previous studies developed polygenic risk scores (PRS) for PDAC risk.

Purpose of the Study:

  • To compare the performance of existing PRS models in an independent cohort.
  • To assess if PRS can differentiate between NODM and long-standing DM patients with PDAC.
  • To evaluate the utility of PRS in identifying individuals for PDAC screening.

Main Methods:

  • Utilized UK Biobank data: 1042 PDAC cases and 10,420 controls.
  • Calculated five PRS models using SNPs from prior studies and a combined model.
  • Employed regression and ROC curve analyses (AUC) to evaluate PRS performance for PDAC risk classification.

    • Main Results:

    • The combined PRS model demonstrated the highest AUC (0.605) and improved a clinical risk model (AUC=0.83).
    • Individuals in the highest quintile of PRS had a 2.74-fold increased PDAC risk.
    • Positive predictive values for PDAC were 11.9% (no DM), 23.9% (long-standing DM), and 86.7% (NODM).

    Conclusions:

    • PDAC-associated genetic variants show a stronger association with DM.
    • PRS holds potential for targeted PDAC secondary screening in individuals with NODM.