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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
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.